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TerminatedNCT03259308FIGARO UC 302Updated Apr 26, 2021Results posted

Efficacy and Safety Study of SHP647 as Induction Therapy in Participants With Moderate to Severe Ulcerative Colitis

A Phase 3 interventional study of Ontamalimab and Placebo in Ulcerative Colitis, sponsored by Shire. Terminated at 207 sites in 22 countries. Open to participants aged 16 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-04-26.

Sponsored by Shire · Phase 3, Interventional, and Treatment

Why this study was terminated
Sponsor decision to discontinue the SHP647 (ontamalimab) clinical trial development program for inflammatory bowel diseases (IBD) early.
Phase
Phase 3
Study type
Interventional
Enrollment
279
Allocation
Randomized
Ages
16 Years to 80 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate the efficacy of SHP647 in inducing remission, based on composite score of patient-reported symptoms and centrally read endoscopy, in participants with moderate to severe ulcerative colitis (UC).

Read the detailed description

27Mar2020: Enrollment of new patients into this study has been paused due to the COVID-19 situation. The duration of this pause is dependent on the leveling and control of the COVID-19 pandemic.

02

Conditions studied

  • Ulcerative Colitis
03

Who can participate

Ages eligible
16 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Participants and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
  • Participants must be able to voluntarily provide written, signed, and dated informed consent and/or assent, as applicable, to participate in the study.
  • Participants less than (\<) 18 years of age must weigh >=40 kg and must have body mass index (BMI) >=16.5 kilogram per square metre (kg/m\^2).

  • Participants must have a documented diagnosis of UC for >=3 months before screening. The following must be available in each participant's source documentation:

    a. A biopsy report to confirm the histological diagnosis. b. A report documenting disease duration based upon prior colonoscopy. Note: If this documentation is not available at the time of screening, a colonoscopy with biopsy to confirm the diagnosis is required during the screening period.

  • Participants must be willing to undergo a flexible sigmoidoscopy or colonoscopy, including biopsy sample collection, during screening after all other inclusion criteria have been met.
  • Participants must have moderate to severe active UC, defined as a total Mayo score of >=6, including a centrally read endoscopic subscore >=2, rectal bleeding subscore >=1, and stool frequency subscore >=1 at baseline.
  • Participants must have evidence of UC extending proximal to the rectum (ie, not limited to proctitis).
  • Participants must have had an inadequate response to, or lost response to, or had an intolerance to at least 1 conventional treatment such as mesalamine (5-aminosalicylate [ASA]), glucocorticoids, immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]), or anti-tumor necrosis factor (TNF).
  • Participants receiving any treatment(s) for UC are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
  • Participants are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the contraceptive requirements of the protocol, or females of nonchildbearing potential.

Exclusion criteria

Exclusion Criteria:

  • Participants with indeterminate colitis, microscopic colitis, non-steroidal anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn's disease.
  • Participants with colonic dysplasia or neoplasia. (Participants with prior history of adenomatous polyps will be eligible if the polyps have been completely removed.)
  • Participants with past medical history or presence of toxic megacolon.
  • Participants with colonic stricture, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for UC during the treatment period.
  • Participants at risk for colorectal cancer must have a colonoscopy performed during the screening period with results available within 10 days before the baseline visit, unless the participant has had a surveillance colonoscopy performed within 1 year prior to screening, and any adenomatous polyps found at that examination have been excised. Colonoscopy report and pathology report (if biopsies are obtained) from the colonoscopy performed during screening or in the prior year confirming no evidence of dysplasia and colon cancer must be available in the source documents.

Participants at risk for colorectal cancer include, but are not limited to:

  1. Participants with extensive colitis for >=8 years or disease limited to left side of colon (ie, distal to splenic flexure) for >=10 years before screening, regardless of age.

  2. Participants >=50 years of age at the time of signing of the informed consent form.

    • Participants have had prior treatment with ontamalimab (formerly PF-00547659, SHP647).
    • Participants with known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.
    • Participants have received anti-TNF treatment within 60 days before baseline.
    • Participants have received any biologic with immunomodulatory properties (other than anti-TNFs) within 90 days before baseline.
    • Participants have received any nonbiologic treatment with immunomodulatory properties (other than their current background UC treatment) within 30 days before baseline.
    • Participants have ever received anti-integrin/adhesion molecule treatment (example (eg): natalizumab, vedolizumab, efalizumab, etrolizumab, or any other investigational anti-integrin/adhesion molecule).
    • Participants have received parenteral or rectal glucocorticoids, or rectal 5-ASA, within 14 days before screening endoscopic procedure.
    • Participants have received leukocyte apheresis or selective lymphocyte, monocyte, or granulocyte apheresis or plasma exchange within 30 days before baseline.
    • Participants have participated in other investigational studies within either 30 days or 5 half-lives of investigational product used in the study (whichever is longer) before baseline.
    • Participants have received a live (attenuated) vaccine within 30 days before the baseline visit.
    • Participants with active enteric infections (positive stool culture and sensitivity), Clostridium difficile infection or pseudomembranous colitis [Participants with C. difficile infection at screening may be allowed re-test after treatment], evidence of active cytomegalovirus infection or Listeria monocytogenes, known active invasive fungal infections such as histoplasmosis or parasitic infections, clinically significant underlying disease that could predispose the participants to infections, or a history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before the baseline visit.
    • Participants with abnormal chest x-ray findings at screening, such as presence of active tuberculosis (TB), general infections, heart failure, or malignancy.
    • Participants with evidence of active or latent infection with Mycobacterium TB or participants with this history who have not completed a generally accepted full course of treatment before randomization are excluded. All other participants must have either the Mantoux (purified protein derivative [PPD]) tuberculin skin test or interferon gamma release assay (IGRA) performed.

Participants who have no history of previously diagnosed active or latent TB are excluded if they have a positive Mantoux (PPD) tuberculin skin test (ie >=5 millimeter [mm] induration) or a positive IGRA (the latter to be tested at the site's local laboratory) during screening or within 12 weeks before screening. If IGRA test cannot be performed locally, a central laboratory may be used, with prior agreement from the sponsor.

  1. An IGRA is strongly recommended for participants with a prior Bacillus Calmette-Guerin (BCG) vaccination, but may be used for any participant. Documentation of IGRA product used and the test result must be in the participant's source documentation if performed locally. Acceptable IGRA products include QuantiFERON TB Gold Plus In-Tube Test.
  2. If the results of the IGRA are indeterminate, the test may be repeated, and if a negative result is obtained, enrollment may proceed. In participants with no history of treated active or latent TB, a positive test on repeat will exclude the participant. Participants with a history of active or latent TB infection must follow instructions for "Participants with a prior diagnosis of active or latent TB are excluded unless both of the following criteria are met" in this criterion.
  3. Participants with repeat indeterminate IGRA results, with no prior TB history, may be enrolled after consultation with a pulmonary or infectious disease specialist who determines low risk of infection (ie, participant would be acceptable for immunosuppressant [eg, anti-TNF] treatment without additional action). This consultation must be included in source documentation.

Results from a chest x-ray, taken within the 12 weeks before or during screening must show no abnormalities suggestive of active TB infection as determined by a qualified medical specialist.

Participants with a prior diagnosis of active or latent TB are excluded unless both of the following criteria are met:

  1. The participant has previously received an adequate course of treatment for either latent (eg, 9 months of isoniazid or an acceptable alternative regimen, in a locale where rates of primary multidrug TB resistance are \<5%. Participants from regions with higher rates of primary multidrug TB resistance are excluded) or active (acceptable multidrug regimen) TB infection. Evidence of diagnosis and treatment must be included in source documentation. Consultation with a pulmonary or infectious disease specialist to confirm adequate treatment (ie, participant would be acceptable for immunosuppressant [eg, anti-TNF] treatment without additional action) must be performed during the screening period. The consultation report must be included in source documentation prior to enrollment.

  2. A chest x-ray performed within 12 weeks before screening or during screening indicates no evidence of active or recurrent disease, and documentation of interpretation by a qualified medical specialist must be included in source documentation.

    • Participants with a pre-existing demyelinating disorder such as multiple sclerosis or new onset seizures, unexplained sensory motor, or cognitive behavioral, neurological deficits, or significant abnormalities noted during screening.
    • Participants with any unexplained symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on the targeted neurological assessment during the screening period.
    • Participants with a transplanted organ. Skin grafts to treat pyoderma gangrenosum are allowed.
    • Participants with a significant concurrent medical condition at the time of screening or baseline, including, but not limited to, the following:

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  1. Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal (except disease under study), endocrine, cardiovascular, pulmonary, immunologic [eg, Felty's syndrome], or local active infection/infectious illness) that, in the investigator's judgment will substantially increase the risk to the participant if he or she participates in the study.
  2. Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence).
  3. Presence of acute coronary syndrome (eg, acute myocardial infarction, unstable angina pectoris) within 24 weeks before screening.

  4. History of significant cerebrovascular disease within 24 weeks before screening.

    • Participants who have had significant trauma or major surgery within 4 weeks before the screening visit, or with any major elective surgery scheduled to occur during the study.
    • Participants with evidence of cirrhosis with or without decompensation.
    • Participants with primary sclerosing cholangitis.
    • Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb).

    Note: If a participant tests negative for HBsAg, but positive for HBcAb, the participant would be considered eligible if no presence of hepatitis B virus (HBV) DNA is confirmed by HBV DNA polymerase chain reaction (PCR) reflex testing performed in the central laboratory.

    • Participants with chronic hepatitis C virus (HCV) (positive HCV antibody [HCVAb] and HCVRNA).

    Note: Participants who are HCVAb positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCVRNA at least 12 weeks prior to baseline]).

    • Participants with any of the following abnormalities in hematology and/or serum chemistry profiles during screening.

    Note: Screening laboratory tests, if the results are considered by the investigator to be transient and inconsistent with the participant's clinical condition, may be repeated once during the screening period for confirmation. Results must be reviewed for eligibility prior to the screening endoscopy procedure.

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  1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels >=3.0×upper limit of normal (ULN).
  2. Total bilirubin level >=1.5×ULN or >2.0×ULN if the participant has a known documented history of Gilbert's syndrome.
  3. Hemoglobin level \<=80 gram per liter (g/L) (8.0 gram per deciliter [g/dL]).
  4. Platelet count \<=100×10\^9 per liter (/L) (100,000 cells per cubic millimeter [mm\^3]) or >=1000×10\^9/L (1,000,000 cells/mm\^3).

  5. White blood cell count \<=3.5×10\^9/L (3500 cells/mm\^3).

    • Absolute neutrophil count (ANC)\<2×10\^9/L (2000 cells/mm\^3).
    • Serum creatinine level >1.5 × ULN or estimated glomerular filtration rate \<30 ml/min/1.73m\^2 based on the abbreviated Modification of Diet in Renal Disease Study Equation.

    Note: If platelet count is \<150,000 cells/mm\^3, a further evaluation should be performed to rule out cirrhosis, unless another etiology has already been identified.

    • Participants with known human immunodeficiency virus (HIV) infection based on documented history, with positive serological test, or positive HIV serologic test at screening, tested at the site's local laboratory in accordance with country requirements or tested at the central laboratory.

    Note: A documented negative HIV test within 6 months of screening is acceptable and does not need to be repeated.

    • Participants who have, or who have a history of (within 2 years before screening), serious psychiatric disease, alcohol dependency, or substance/drug abuse or dependency of any kind, including abuse of medical marijuana (cannabis).
    • Participants with any other severe acute or chronic medical or psychiatric condition or laboratory or electrocardiogram (ECG) abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
    • Female participants who are planning to become pregnant during the study period.
    • Participants who do not agree to postpone donation of any organ or tissue, including male participants who are planning to bank or donate sperm and female participants who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product.
    • Participants who are investigational site staff members or relatives of those site staff members or Participants who are Shire employees directly involved in the conduct of the study.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
279 participants (actual)

Study arms

  • Experimental
    Ontamalimab 25 mg

    Participants will receive 25 milligram (mg) of ontamalimab subcutaneous (SC) injection using a prefilled syringe (PFS) on Week 0, Week 4 and Week 8.

    Drug: Ontamalimab

  • Experimental
    Ontamalimab 75 mg

    Participants will receive 75 mg of ontamalimab SC injection using PFS on Week 0, Week 4 and Week 8.

    Drug: Ontamalimab

  • Placebo comparator
    Placebo

    Participants will receive placebo matched to ontamalimab SC injection using PFS on Week 0, Week 4, and Week 8.

    Drug: Placebo

Interventions

  • DrugOntamalimab

    Participants will receive 1 mL of ontamalimab sterile aqueous buffered solution at an appropriate concentration to provide the intended dose of drug (25 or 75 mg).

    Also known as: SHP647, PF- 00547659

  • DrugPlacebo

    Participants will receive 1 mL of sterile aqueous buffered solution.

05

What researchers measure

Primary outcomes

  1. Number of Participants With Remission Based on Composite Score at Week 12

    Remission was defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy as stool frequency sub-score of 0 or 1 with at least a 1-point change from baseline, rectal bleeding sub-score of 0 and endoscopic sub-score of 0 or 1 (modified, excluded friability). The composite score was a recommended measure derived from the Mayo score without the physician global assessment (PGA) sub-score and ranged from 0 to 9 points. The Mayo score was a measure of Ulcerative Colitis (UC) disease activity. It ranged from 0 to 12 points and consisted of 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease. The sub-scores were stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).

    Time frame: At Week 12

Secondary outcomes

  1. Number of Participants With Endoscopic Remission at Week 12

    Endoscopic remission was defined by centrally read endoscopic sub-score 0 or 1 (modified, excluded friability). The centrally read endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease.

    Time frame: At Week 12

  2. Number of Participants With Clinical Remission at Week 12

    Clinical remission was defined by stool frequency sub-score of 0 or 1 with at least a 1-point change from baseline in stool frequency sub-score, and rectal bleeding sub-score of 0. The stool frequency sub-score and rectal bleeding sub-score ranged from 0 to 3 with higher scores indicating more severe disease.

    Time frame: At Week 12

  3. Number of Participants With Clinical Response Based on Composite Score at Week 12

    Clinical response based on composite score was defined as a decrease from baseline in the composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30 percent (%), with an accompanying decrease in the sub-score for rectal bleeding greater than or equal to (\>=) 1 point or a sub-score for rectal bleeding less than or equal to (\<=) 1. The composite score was a recommended measure derived from the Mayo score without the PGA sub-score and ranged from 0 to 9 points. The Mayo score was a measure of UC disease activity. It ranged from 0 to 12 points and consisted of 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease The sub-scores were stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).

    Time frame: At Week 12

  4. Number of Participants With Mucosal Healing Based on Endoscopic and Histological Assessment Using the Geboes Score Grading System at Week 12

    Mucosal healing was defined by centrally read endoscopic sub-score 0 or 1 (modified, excluded friability) and centrally read Geboes score of \<=2. The centrally read endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, was a validated score for evaluating histologic disease activity in UC as follows: grade 0 equal to (=) structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicating more severe disease. Number of participants with mucosal healing based on endoscopic and histological assessment using the Geboes score grading system were reported.

    Time frame: At Week 12

  5. Number of Participants With Remission Based on Total Mayo Score at Week 12

    Remission was defined as a Total Mayo score of \<=2 with no individual sub-score (stool frequency, rectal bleeding, endoscopy \[modified, excluded friability\], and PGA) exceeding 1, at the Week 12. The Total Mayo score ranged from 0 to 12 points and consisted of 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease: stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).

    Time frame: At Week 12

  6. Number of Participants With Clinical Response Based on Total Mayo Score at Week 12

    Clinical response (Mayo) was defined as a decrease from baseline in the Total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the sub-score for rectal bleeding \>=1 point or an absolute sub-score for rectal bleeding \<=1. The Total Mayo score ranged from 0 to 12 points and consisted of the following 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease: stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).

    Time frame: At Week 12

  7. Number of Participants With Partial Mayo Score <=2 With no Individual Sub-score Greater Than (>) 1 at Weeks 4, 8, and 12

    The partial Mayo score ranged from 0 to 9 points and consisted of the following 3 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); PGA (0-3). The partial Mayo score did not include the endoscopy sub-score.

    Time frame: At Weeks 4, 8, and 12

  8. Number of Participants With Clinical Remission With Stool Frequency Sub-scores of 0 or 1 and Rectal Bleeding Sub-score of 0 at Weeks 4 and 8

    Number of participants were reported with stool frequency sub-scores of 0 or 1 and rectal bleeding sub-score of 0. Clinical remission was defined as stool frequency sub-score of 0 or 1 with at least a 1-point change from baseline in stool frequency sub-score, and a rectal bleeding sub-score of 0. The stool frequency sub-score and rectal bleeding sub-score of Mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

    Time frame: At Weeks 4 and 8

  9. Number of Participants With Endoscopic Remission With Sub-score of 0 at Week 12

    Endoscopic remission was defined by centrally read endoscopic sub-score 0 (modified, excluded friability). The centrally read endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease.

    Time frame: At Week 12

  10. Number of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Sub-scores of 0 at Weeks 4, 8, and 12

    Number of participants were reported with rectal bleeding and stool frequency sub-scores of 0. Clinical remission was defined as both rectal bleeding and stool frequency sub-scores of 0. The stool frequency sub-score and rectal bleeding sub-score of Mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

    Time frame: At Weeks 4, 8, and 12

  11. Number of Participants With Deep Remission at Week 12

    Deep remission was defined as both endoscopic and rectal bleeding sub-scores of 0, and stool frequency sub-score \<=1 and a centrally read Geboes score of \<=2. The stool frequency sub-score, rectal bleeding sub-score and endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease. The composite score was a recommended measure consisted of the Mayo score without the PGA sub-score and ranged from 0 to 9 points. Geboes score grading system was a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicating more severe disease.

    Time frame: At Week 12

  12. Change From Baseline in Average Worst Abdominal Pain Score Based on Patient Reported Outcome-ulcerative Colitis (PRO-UC) Daily e-Diary at Week 12

    PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data of abdominal pain worst severity, as experienced over the previous 24 hours, in the e-diary. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or non-consecutive) of last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Abdominal pain's worst severity assessment was based on an 11-point numerical rating scale with 0 anchor at "No pain" and 10 at "Worst Imaginable Pain" as experienced over the previous 24 hours, in the e-diary. Higher scores indicating more severe pain.

    Time frame: Baseline, Week 12

  13. Change From Baseline in Diarrhea (Average Loose Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12

    PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for number of loose bowel movement, as experienced over the previous 24 hours, in the e-diary. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number of loose bowel movement ranged from 0-27. Higher scores indicating more frequent bowel movements.

    Time frame: Baseline, Week 12

  14. Change From Baseline in Average Bowel Movements With Urgency Score Based on PRO-UC Daily e-Diary at Week 12

    PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for number of bowel movement with urgency, as experienced over the previous 24 hours. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number bowel movements urgency ranged from 0 to 27. Higher scores indicating more frequent bowel movements.

    Time frame: Baseline, Week 12

  15. Change From Baseline in Absolute Stool Frequency (Average Number of Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12

    PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for average number of bowel movements, as experienced over the previous 24 hours. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number bowel movements ranged from 0 to 27. Higher scores indicating more frequent bowel movements.

    Time frame: Baseline, Week 12

  16. Change From Baseline in Absolute Rectal Bleeding (Average Number Bowel Movements With Blood) Score Based on PRO-UC Daily e-Diary at Week 12

    PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for average number of bowel movements with blood, as experienced over the previous 24 hours. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number bowel movements with blood ranged from 0 to 27. Higher scores indicating more frequent bowel movements with blood.

    Time frame: Baseline, Week 12

  17. Change From Baseline in Total Sign/Symptom Score Based on PRO-UC Daily e-Diary at Week 12

    Total sign/symptom score was the average of the average scores of worst abdominal pain over the past 24 hours and the conversion scale values for number of bowel movements blood, number of bowel movements with urgency, number of bowel movements and number of loose bowel movements, with scale ranged of 0-10, with higher scores indicating higher severity.

    Time frame: Baseline, Week 12

  18. Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains Scores at Weeks 8 and 12

    IBDQ was a psychometrically validated participant-reported outcome (PRO) instrument for measuring the disease-specific health-related quality of life (HRQL) in participants with inflammatory bowel disease, including UC. The IBDQ consisted of 32 items, which were grouped into 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. The 4 domains were scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. Higher scores indicating a better quality of life.

    Time frame: Baseline, Weeks 8 and 12

  19. Change From Baseline in IBDQ Total Scores at Weeks 8 and 12

    IBDQ was a psychometrically validated PRO instrument for measuring the disease-specific HRQL in participants with inflammatory bowel disease, included UC. The IBDQ consisted of 32 items, which were grouped into 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. The 4 domains were scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. The total IBDQ score ranged from 32 to 224. For the total score and each domain, a higher score indicating better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points was considered to indicate a clinically meaningful improvement.

    Time frame: Baseline, Weeks 8 and 12

  20. Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Week 12

    SF-36 was a generic quality-of-life instrument that had been widely used to assess health-related quality of life (HRQL) of participants. SF-36 consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning \[1=yes, limited a lot to 3=no, not limited at all\], role-physical \[1=all of the time to 5=none of the time\], bodily pain \[1=very severe to 6=none\], general health \[1=poor to 5=excellent\], vitality \[1=none of the time to 5=all of the time\], social functioning \[1=all of the time: to 5=none of the time\], role emotional \[1=all of the time to 5=none of the time\] and mental health \[1=all of the time to 5=none of the time\]). Four domains comprised physical component summary (PCS) score (physical functioning, role-physical, bodily pain, general health) and remaining 4 domains comprised mental component summary (MCS) score (vitality, social functioning, role-emotional, mental health). The scores ranged from 0 to 100. Higher scores indicating better HRQL.

    Time frame: Baseline, Week 12

  21. Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Individual Domain Scores) at Week 12

    SF-36 was a generic quality-of-life instrument that had been widely used to assess HRQL of participants. Generic instruments were used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning \[1=yes, limited a lot to 3=no, not limited at all\], role-physical \[1=all of the time to 5=none of the time\], bodily pain \[1=very severe to 6=none\], general health \[1=poor to 5=excellent\], vitality \[1=none of the time to 5=all of the time\], social functioning \[1=all of the time: to 5=none of the time\], role emotional \[1=all of the time to 5=none of the time\] and mental health \[1=all of the time to 5=none of the time\]), with scores ranged from 0 to 100. Higher scores indicating better HRQL.

    Time frame: Baseline, Week 12

  22. Number of Participants Based on Inpatient Hospitalization

    Number of participants based on inpatient hospitalization due to all-cause hospitalization, gastrointestinal related, other illness/problem, and undergo gastrointestinal related procedures during the entire study period were reported.

    Time frame: From start of study up to follow up (Week 29)

  23. Median Duration of Total Inpatient Days

    Inpatient days were calculated as Date of discharge - Date of admission + 1. Median duration of total inpatient days during the entire study period was reported.

    Time frame: From start of study up to follow-up (Week 29)

06

Results

Posted Apr 26, 2021
Limitations and caveats
The study was terminated as per the sponsor decision to discontinue the SHP647 (ontamalimab) clinical trial development program for inflammatory bowel diseases (IBD) early.

Participant flow

The study was conducted at 205 sites between 5 December 2017 (first participant first visit) and 06 October 2020 (last participant last visit).

Participant flow — Overall Study
MilestonePlaceboOntamalimab 25 mgOntamalimab 75 mg
Started56111112
Completed49103105
Not completed787
Withdrew: Adverse event541
Withdrew: Withdrawal by subject213
Withdrew: Lost to follow-up001
Withdrew: Pregnancy001
Withdrew: Protocol deviation030
Withdrew: Lack of efficacy001

Outcome measures

PrimaryNumber of Participants With Remission Based on Composite Score at Week 12

Remission was defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy as stool frequency sub-score of 0 or 1 with at least a 1-point change from baseline, rectal bleeding sub-score of 0 and endoscopic sub-score of 0 or 1 (modified, excluded friability). The composite score was a recommended measure derived from the Mayo score without the physician global assessment (PGA) sub-score and ranged from 0 to 9 points. The Mayo score was a measure of Ulcerative Colitis (UC) disease activity. It ranged from 0 to 12 points and consisted of 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease. The sub-scores were stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).

Time frame:
At Week 12
Reported as:
Count of participants · Participants
Number of Participants With Remission Based on Composite Score at Week 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
Number of Participants With Remission Based on Composite Score at Week 1273033
Statistical analysis
  • Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = 0.027P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
  • Placebo vs Ontamalimab 75 mg · Cochran-Mantel-Haenszel · p = 0.014P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
SecondaryNumber of Participants With Endoscopic Remission at Week 12

Endoscopic remission was defined by centrally read endoscopic sub-score 0 or 1 (modified, excluded friability). The centrally read endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease.

Time frame:
At Week 12
Reported as:
Count of participants · Participants
Number of Participants With Endoscopic Remission at Week 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
Number of Participants With Endoscopic Remission at Week 1273938
Statistical analysis
  • Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = 0.001P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
  • Placebo vs Ontamalimab 75 mg · Cochran-Mantel-Haenszel · p = 0.003P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
SecondaryNumber of Participants With Clinical Remission at Week 12

Clinical remission was defined by stool frequency sub-score of 0 or 1 with at least a 1-point change from baseline in stool frequency sub-score, and rectal bleeding sub-score of 0. The stool frequency sub-score and rectal bleeding sub-score ranged from 0 to 3 with higher scores indicating more severe disease.

Time frame:
At Week 12
Reported as:
Count of participants · Participants
Number of Participants With Clinical Remission at Week 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
Number of Participants With Clinical Remission at Week 12105056
Statistical analysis
  • Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = <0.001P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
  • Placebo vs Ontamalimab 75 mg · Cochran-Mantel-Haenszel · p = <0.001P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
SecondaryNumber of Participants With Clinical Response Based on Composite Score at Week 12

Clinical response based on composite score was defined as a decrease from baseline in the composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30 percent (%), with an accompanying decrease in the sub-score for rectal bleeding greater than or equal to (\>=) 1 point or a sub-score for rectal bleeding less than or equal to (\<=) 1. The composite score was a recommended measure derived from the Mayo score without the PGA sub-score and ranged from 0 to 9 points. The Mayo score was a measure of UC disease activity. It ranged from 0 to 12 points and consisted of 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease The sub-scores were stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).

Time frame:
At Week 12
Reported as:
Count of participants · Participants
Number of Participants With Clinical Response Based on Composite Score at Week 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
Number of Participants With Clinical Response Based on Composite Score at Week 12166764
Statistical analysis
  • Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = <0.001P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
  • Placebo vs Ontamalimab 75 mg · Cochran-Mantel-Haenszel · p = <0.001P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
SecondaryNumber of Participants With Mucosal Healing Based on Endoscopic and Histological Assessment Using the Geboes Score Grading System at Week 12

Mucosal healing was defined by centrally read endoscopic sub-score 0 or 1 (modified, excluded friability) and centrally read Geboes score of \<=2. The centrally read endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, was a validated score for evaluating histologic disease activity in UC as follows: grade 0 equal to (=) structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicating more severe disease. Number of participants with mucosal healing based on endoscopic and histological assessment using the Geboes score grading system were reported.

Time frame:
At Week 12
Reported as:
Count of participants · Participants
Number of Participants With Mucosal Healing Based on Endoscopic and Histological Assessment Using the Geboes Score Grading System at Week 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
Number of Participants With Mucosal Healing Based on Endoscopic and Histological Assessment Using the Geboes Score Grading System at Week 1263530
Statistical analysis
  • Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = 0.002P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
  • Placebo vs Ontamalimab 75 mg · Cochran-Mantel-Haenszel · p = 0.017P-value was based on Cochran-Mantel-Haenszel chi-square test stratified by actual status of prior anti-TNF treatment and glucocorticoid at baseline.
SecondaryNumber of Participants With Remission Based on Total Mayo Score at Week 12

Remission was defined as a Total Mayo score of \<=2 with no individual sub-score (stool frequency, rectal bleeding, endoscopy \[modified, excluded friability\], and PGA) exceeding 1, at the Week 12. The Total Mayo score ranged from 0 to 12 points and consisted of 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease: stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).

Time frame:
At Week 12
Reported as:
Count of participants · Participants
Number of Participants With Remission Based on Total Mayo Score at Week 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
Number of Participants With Remission Based on Total Mayo Score at Week 1252826
SecondaryNumber of Participants With Clinical Response Based on Total Mayo Score at Week 12

Clinical response (Mayo) was defined as a decrease from baseline in the Total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the sub-score for rectal bleeding \>=1 point or an absolute sub-score for rectal bleeding \<=1. The Total Mayo score ranged from 0 to 12 points and consisted of the following 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease: stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).

Time frame:
At Week 12
Reported as:
Count of participants · Participants
Number of Participants With Clinical Response Based on Total Mayo Score at Week 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
Number of Participants With Clinical Response Based on Total Mayo Score at Week 12196663
SecondaryNumber of Participants With Partial Mayo Score <=2 With no Individual Sub-score Greater Than (>) 1 at Weeks 4, 8, and 12

The partial Mayo score ranged from 0 to 9 points and consisted of the following 3 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); PGA (0-3). The partial Mayo score did not include the endoscopy sub-score.

Time frame:
At Weeks 4, 8, and 12
Reported as:
Count of participants · Participants
Number of Participants With Partial Mayo Score <=2 With no Individual Sub-score Greater Than (>) 1 at Weeks 4, 8, and 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
At Week 462623
At Week 8125341
At Week 12104952
SecondaryNumber of Participants With Clinical Remission With Stool Frequency Sub-scores of 0 or 1 and Rectal Bleeding Sub-score of 0 at Weeks 4 and 8

Number of participants were reported with stool frequency sub-scores of 0 or 1 and rectal bleeding sub-score of 0. Clinical remission was defined as stool frequency sub-score of 0 or 1 with at least a 1-point change from baseline in stool frequency sub-score, and a rectal bleeding sub-score of 0. The stool frequency sub-score and rectal bleeding sub-score of Mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

Time frame:
At Weeks 4 and 8
Reported as:
Count of participants · Participants
Number of Participants With Clinical Remission With Stool Frequency Sub-scores of 0 or 1 and Rectal Bleeding Sub-score of 0 at Weeks 4 and 8
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
At Week 442822
At Week 8105256
SecondaryNumber of Participants With Endoscopic Remission With Sub-score of 0 at Week 12

Endoscopic remission was defined by centrally read endoscopic sub-score 0 (modified, excluded friability). The centrally read endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease.

Time frame:
At Week 12
Reported as:
Count of participants · Participants
Number of Participants With Endoscopic Remission With Sub-score of 0 at Week 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
Number of Participants With Endoscopic Remission With Sub-score of 0 at Week 1211414
SecondaryNumber of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Sub-scores of 0 at Weeks 4, 8, and 12

Number of participants were reported with rectal bleeding and stool frequency sub-scores of 0. Clinical remission was defined as both rectal bleeding and stool frequency sub-scores of 0. The stool frequency sub-score and rectal bleeding sub-score of Mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

Time frame:
At Weeks 4, 8, and 12
Reported as:
Count of participants · Participants
Number of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Sub-scores of 0 at Weeks 4, 8, and 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
At Week 401512
At Week 852919
At Week 1263626
SecondaryNumber of Participants With Deep Remission at Week 12

Deep remission was defined as both endoscopic and rectal bleeding sub-scores of 0, and stool frequency sub-score \<=1 and a centrally read Geboes score of \<=2. The stool frequency sub-score, rectal bleeding sub-score and endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease. The composite score was a recommended measure consisted of the Mayo score without the PGA sub-score and ranged from 0 to 9 points. Geboes score grading system was a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicating more severe disease.

Time frame:
At Week 12
Reported as:
Count of participants · Participants
Number of Participants With Deep Remission at Week 12
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
Number of Participants With Deep Remission at Week 121119
SecondaryChange From Baseline in Average Worst Abdominal Pain Score Based on Patient Reported Outcome-ulcerative Colitis (PRO-UC) Daily e-Diary at Week 12

PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data of abdominal pain worst severity, as experienced over the previous 24 hours, in the e-diary. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or non-consecutive) of last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Abdominal pain's worst severity assessment was based on an 11-point numerical rating scale with 0 anchor at "No pain" and 10 at "Worst Imaginable Pain" as experienced over the previous 24 hours, in the e-diary. Higher scores indicating more severe pain.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Average Worst Abdominal Pain Score Based on Patient Reported Outcome-ulcerative Colitis (PRO-UC) Daily e-Diary at Week 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
Change From Baseline in Average Worst Abdominal Pain Score Based on Patient Reported Outcome-ulcerative Colitis (PRO-UC) Daily e-Diary at Week 12-1.69 ± 0.309-2.49 ± 0.218-1.83 ± 0.215
SecondaryChange From Baseline in Diarrhea (Average Loose Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12

PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for number of loose bowel movement, as experienced over the previous 24 hours, in the e-diary. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number of loose bowel movement ranged from 0-27. Higher scores indicating more frequent bowel movements.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Diarrhea (Average Loose Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
Change From Baseline in Diarrhea (Average Loose Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12-1.41 ± 0.405-3.50 ± 0.286-2.87 ± 0.284
SecondaryChange From Baseline in Average Bowel Movements With Urgency Score Based on PRO-UC Daily e-Diary at Week 12

PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for number of bowel movement with urgency, as experienced over the previous 24 hours. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number bowel movements urgency ranged from 0 to 27. Higher scores indicating more frequent bowel movements.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Average Bowel Movements With Urgency Score Based on PRO-UC Daily e-Diary at Week 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
Change From Baseline in Average Bowel Movements With Urgency Score Based on PRO-UC Daily e-Diary at Week 12-1.09 ± 0.373-2.87 ± 0.263-2.56 ± 0.264
SecondaryChange From Baseline in Absolute Stool Frequency (Average Number of Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12

PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for average number of bowel movements, as experienced over the previous 24 hours. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number bowel movements ranged from 0 to 27. Higher scores indicating more frequent bowel movements.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Absolute Stool Frequency (Average Number of Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
Change From Baseline in Absolute Stool Frequency (Average Number of Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12-1.26 ± 0.386-3.32 ± 0.272-2.97 ± 0.272
SecondaryChange From Baseline in Absolute Rectal Bleeding (Average Number Bowel Movements With Blood) Score Based on PRO-UC Daily e-Diary at Week 12

PRO-UC signs and symptom data were collected using a daily e-diary during treatment period. Collection of daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for average number of bowel movements with blood, as experienced over the previous 24 hours. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number bowel movements with blood ranged from 0 to 27. Higher scores indicating more frequent bowel movements with blood.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Absolute Rectal Bleeding (Average Number Bowel Movements With Blood) Score Based on PRO-UC Daily e-Diary at Week 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
Change From Baseline in Absolute Rectal Bleeding (Average Number Bowel Movements With Blood) Score Based on PRO-UC Daily e-Diary at Week 12-2.05 ± 0.379-3.74 ± 0.267-3.41 ± 0.265
SecondaryChange From Baseline in Total Sign/Symptom Score Based on PRO-UC Daily e-Diary at Week 12

Total sign/symptom score was the average of the average scores of worst abdominal pain over the past 24 hours and the conversion scale values for number of bowel movements blood, number of bowel movements with urgency, number of bowel movements and number of loose bowel movements, with scale ranged of 0-10, with higher scores indicating higher severity.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Total Sign/Symptom Score Based on PRO-UC Daily e-Diary at Week 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
Change From Baseline in Total Sign/Symptom Score Based on PRO-UC Daily e-Diary at Week 12-1.15 ± 0.246-2.32 ± 0.173-2.00 ± 0.172
SecondaryChange From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains Scores at Weeks 8 and 12

IBDQ was a psychometrically validated participant-reported outcome (PRO) instrument for measuring the disease-specific health-related quality of life (HRQL) in participants with inflammatory bowel disease, including UC. The IBDQ consisted of 32 items, which were grouped into 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. The 4 domains were scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. Higher scores indicating a better quality of life.

Time frame:
Baseline, Weeks 8 and 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains Scores at Weeks 8 and 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
IBDQ Bowel Function Dimension Score: Change at Week 89.59 ± 1.61116.66 ± 1.18915.36 ± 1.180
IBDQ Bowel Function Dimension Score: Change at Week 129.51 ± 1.70717.71 ± 1.25015.86 ± 1.232
IBDQ Emotional Status Dimension Score: Change at Week 88.91 ± 1.70115.18 ± 1.25514.41 ± 1.247
IBDQ Emotional Status Dimension Score: Change at Week 129.94 ± 1.86114.84 ± 1.35914.73 ± 1.341
IBDQ Systemic Symptoms Dimension Score: Change at Week 83.84 ± 0.7596.61 ± 0.5615.86 ± 0.557
IBDQ Systemic Symptoms Dimension Score: Change at Week 123.85 ± 0.8147.34 ± 0.5966.04 ± 0.587
IBDQ Social Function Dimension Score: Change at Week 85.06 ± 0.8736.97 ± 0.6436.75 ± 0.640
IBDQ Social Function Dimension Score: Change at Week 125.09 ± 0.9267.68 ± 0.6777.03 ± 0.668
SecondaryChange From Baseline in IBDQ Total Scores at Weeks 8 and 12

IBDQ was a psychometrically validated PRO instrument for measuring the disease-specific HRQL in participants with inflammatory bowel disease, included UC. The IBDQ consisted of 32 items, which were grouped into 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. The 4 domains were scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. The total IBDQ score ranged from 32 to 224. For the total score and each domain, a higher score indicating better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points was considered to indicate a clinically meaningful improvement.

Time frame:
Baseline, Weeks 8 and 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in IBDQ Total Scores at Weeks 8 and 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
Change at Week 827.56 ± 4.57445.63 ± 3.38042.58 ± 3.358
Change at Week 1228.39 ± 4.99047.75 ± 3.64943.85 ± 3.604
SecondaryChange From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Week 12

SF-36 was a generic quality-of-life instrument that had been widely used to assess health-related quality of life (HRQL) of participants. SF-36 consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning \[1=yes, limited a lot to 3=no, not limited at all\], role-physical \[1=all of the time to 5=none of the time\], bodily pain \[1=very severe to 6=none\], general health \[1=poor to 5=excellent\], vitality \[1=none of the time to 5=all of the time\], social functioning \[1=all of the time: to 5=none of the time\], role emotional \[1=all of the time to 5=none of the time\] and mental health \[1=all of the time to 5=none of the time\]). Four domains comprised physical component summary (PCS) score (physical functioning, role-physical, bodily pain, general health) and remaining 4 domains comprised mental component summary (MCS) score (vitality, social functioning, role-emotional, mental health). The scores ranged from 0 to 100. Higher scores indicating better HRQL.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Week 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
Physical Component Summary: Change at Week 124.84 ± 0.9826.45 ± 0.7215.54 ± 0.709
Mental Component Summary: Change at Week 122.09 ± 1.3017.37 ± 0.9496.68 ± 0.935
SecondaryChange From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Individual Domain Scores) at Week 12

SF-36 was a generic quality-of-life instrument that had been widely used to assess HRQL of participants. Generic instruments were used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning \[1=yes, limited a lot to 3=no, not limited at all\], role-physical \[1=all of the time to 5=none of the time\], bodily pain \[1=very severe to 6=none\], general health \[1=poor to 5=excellent\], vitality \[1=none of the time to 5=all of the time\], social functioning \[1=all of the time: to 5=none of the time\], role emotional \[1=all of the time to 5=none of the time\] and mental health \[1=all of the time to 5=none of the time\]), with scores ranged from 0 to 100. Higher scores indicating better HRQL.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Individual Domain Scores) at Week 12
Score on a ScalePlaceboOntamalimab 25 mgOntamalimab 75 mg
Physical Functioning: Change at Week 123.40 ± 0.9015.03 ± 0.6573.79 ± 0.646
Role-Physical: Change at Week 124.47 ± 1.2057.39 ± 0.8846.90 ± 0.874
Bodily Pain: Change at Week 125.55 ± 1.2938.18 ± 0.9417.06 ± 0.926
General Health: Change at Week 123.93 ± 1.2037.00 ± 0.8806.34 ± 0.865
Vitality: Change at Week 123.59 ± 1.3818.23 ± 1.0087.43 ± 0.993
Social Functioning: Change at Week 123.59 ± 1.2337.43 ± 0.8986.54 ± 0.884
Role-Emotional: Change at Week 121.27 ± 1.3175.79 ± 0.9585.68 ± 0.944
Mental Health: Change at Week 123.56 ± 1.2687.90 ± 0.9256.47 ± 0.911
SecondaryNumber of Participants Based on Inpatient Hospitalization

Number of participants based on inpatient hospitalization due to all-cause hospitalization, gastrointestinal related, other illness/problem, and undergo gastrointestinal related procedures during the entire study period were reported.

Time frame:
From start of study up to follow up (Week 29)
Reported as:
Count of participants · Participants
Number of Participants Based on Inpatient Hospitalization
ParticipantsPlaceboOntamalimab 25 mgOntamalimab 75 mg
All-Cause Hospitalization232
Gastrointestinal Related121
Other Illness/Problem122
Undergo Gastrointestinal Related Procedures100
SecondaryMedian Duration of Total Inpatient Days

Inpatient days were calculated as Date of discharge - Date of admission + 1. Median duration of total inpatient days during the entire study period was reported.

Time frame:
From start of study up to follow-up (Week 29)
Reported as:
Median · Days
Median Duration of Total Inpatient Days
DaysPlaceboOntamalimab 25 mgOntamalimab 75 mg
Median Duration of Total Inpatient Days10.5 (6 to 15)7.0 (6 to 11)2.0 (2 to 2)

Adverse events

Collected over From start of study drug administration up to follow-up (Week 29). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/56 (0%)4/56 (7.1%)7/56 (12.5%)
Ontamalimab 25 mg0/111 (0%)5/111 (4.5%)5/111 (4.5%)
Ontamalimab 75 mg0/112 (0%)3/112 (2.7%)7/112 (6.3%)
Most frequent serious events
Most frequent serious events
EventPlaceboOntamalimab 25 mgOntamalimab 75 mg
Colitis ulcerativeGastrointestinal disorders3/561/1111/112
HydrocalyxRenal and urinary disorders1/560/1110/112
AnaemiaBlood and lymphatic system disorders0/561/1111/112
LeukopeniaBlood and lymphatic system disorders0/561/1110/112
Supraventricular tachycardiaCardiac disorders0/561/1110/112
PneumoniaInfections and infestations0/561/1110/112
Rash pustularInfections and infestations0/561/1110/112
HeadacheNervous system disorders0/561/1110/112
AstheniaGeneral disorders0/560/1111/112
Most frequent other events
Most frequent other events
EventPlaceboOntamalimab 25 mgOntamalimab 75 mg
AnaemiaBlood and lymphatic system disorders4/562/1117/112
NauseaGastrointestinal disorders4/563/1112/112

Baseline characteristics

Safety set consisted of all participants who had received at least 1 dose of investigational product.

Age, Continuous
Age, Continuous(Years)PlaceboOntamalimab 25 mgOntamalimab 75 mgTotal
Mean41.6 ± 13.5043.5 ± 14.1643.9 ± 13.0843.3 ± 13.58
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboOntamalimab 25 mgOntamalimab 75 mgTotal
Female234645114
Male336567165
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboOntamalimab 25 mgOntamalimab 75 mgTotal
Hispanic or Latino5171638
Not Hispanic or Latino519396240
Unknown or Not Reported0101
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboOntamalimab 25 mgOntamalimab 75 mgTotal
Race — American Indian or Alaska Native0538
Race — Asian: Japanese65617
Race — Asian: Korean45817
Race — Asian: Other1001
Race — Black or African American2417
Race — White418588214
Race — Native Hawaiian or Other Pacific Islander0101
Race — Multiple1517
Race — Other (Unspecified)1157
07

Study locations

207 sites
  • Arizona Digestive Health Mesa - East
    Mesa, Arizona 85206, United States
  • Elite Clinical Studies - Phoenix - Clinedge - PPDS
    Phoenix, Arizona 85018, United States
  • Advanced Research Center
    Anaheim, California 92805, United States
  • Kindred Medical Institute for Clinical Trials, LLC
    Corona, California 92879, United States
  • United Medical Doctors
    Encinitas, California 92024, United States
  • University of California San Diego
    La Jolla, California 92037, United States
  • VA Long Beach Healthcare System - NAVREF - PPDS
    Long Beach, California 90822, United States
  • Facey Medical Foundation
    Mission Hills, California 91345, United States
  • United Medical Doctors
    Murrieta, California 92563, United States
  • Alliance Clinical Research-(Vestavia Hills)
    Poway, California 92064, United States
  • University of California San Francisco
    San Francisco, California 94158, United States
  • Care Access Research, San Pablo
    San Pablo, California 94806, United States
  • Renaissance Research Medical Group, INC
    Cape Coral, Florida 33991, United States
  • Gastro Florida
    Clearwater, Florida 33756, United States
  • Hi Tech and Global Research, LLc
    Coral Gables, Florida 33134, United States
  • ENCORE Borland-Groover Clinical Research - ERN - PPDS
    Jacksonville, Florida 32256, United States
  • SIH Research
    Kissimmee, Florida 34741, United States
  • Alliance Medical Research LLC
    Lighthouse Point, Florida 33064, United States
  • Crystal Biomedical Research
    Miami Lakes, Florida 33065, United States
  • Sanchez Clinical Research, Inc
    Miami, Florida 33157, United States
  • Pharma Research International Inc
    Naples, Florida 34110, United States
  • Bayside Clinical Research - New Port Richey
    New Port Richey, Florida 34655, United States
  • Accel Research Sites - St. Petersburg - ERN - PPDS
    Pinellas Park, Florida 33781, United States
  • BRCR Medical Center Inc.
    Plantation, Florida 33322, United States
  • DBC Research
    Tamarac, Florida 33321, United States
  • Infinite Clinical Trials
    Atlanta, Georgia 30349, United States
  • Atlanta Center For Gastroenterology PC
    Decatur, Georgia 30033, United States
  • Atlanta Gastroenterology Specialists, PC
    Suwanee, Georgia 30024, United States
  • Loretto Hospital
    Chicago, Illinois 60644, United States
  • IL Gastroenterology Group
    Gurnee, Illinois 60031, United States
  • Edward Hines Jr VA Hospital - NAVREF - PPDS
    Hines, Illinois 60141, United States
  • Dupage Medical Group
    Oakbrook Terrace, Illinois 60181, United States
  • Gastroenterology Associates of Hazard
    Hazard, Kentucky 41701, United States
  • CroNOLA, LLC.
    Houma, Louisiana 70360, United States
  • Chevy Chase Clinical Research
    Chevy Chase, Maryland 20815, United States
  • Commonwealth Clinical Studies LLC
    Brockton, Massachusetts 02302, United States
  • UMass Memorial Medical Center
    Worcester, Massachusetts 01655, United States
  • University of Michigan
    Ann Arbor, Michigan 48109, United States
  • Clinical Research Institute of Michigan
    Chesterfield, Michigan 48047, United States
  • National Clinical, LLC
    Hamtramck, Michigan 48212, United States
  • Washington University in St. Louis
    Saint Louis, Missouri 63110, United States
  • St Louis Center For Clinical Research
    Saint Louis, Missouri 63128, United States
  • Advanced Biomedical Research of America
    Las Vegas, Nevada 89123, United States
  • Encompass Care
    North Las Vegas, Nevada 89086, United States
  • NYU Langone Long Island Clinical Research Associates
    Great Neck, New York 11021, United States
  • Weill Cornell Medical College
    New York, New York 10021, United States
  • Southtowns Gastroenterology, PLLC
    Orchard Park, New York 14127, United States
  • East Carolina Gastroenterology
    Jacksonville, North Carolina 28546, United States
  • Prestige Clinical Research
    Franklin, Ohio 45005, United States
  • Ohio Clinical Research Partners LLC
    Mentor, Ohio 44060, United States
  • Veteran's Research and Education Foundation - NAVREF - PPDS
    Oklahoma City, Oklahoma 73104, United States
  • Veterans Research Foundation of Pittsburgh - NAVREF - PPDS
    Pittsburgh, Pennsylvania 15240, United States
  • Digestive Health Associates of Texas, P.A.dba DHAT Research Institute
    Garland, Texas 75044, United States
  • Precision Research Institute, LLC
    Houston, Texas 77039, United States
  • Biopharma Informatic Inc.
    Houston, Texas 77043, United States
  • Southwest Clinical Trials
    Houston, Texas 77074, United States
  • Aztec Medical Research
    Houston, Texas 77079, United States
  • BI Research Center
    Houston, Texas 77084, United States
  • Southern Star Research Institute LLC
    San Antonio, Texas 78229, United States
  • Mid Atlantic Health Specialists
    Galax, Virginia 24333, United States
  • Winchester Gastroenterology Associates
    Winchester, Virginia 22601, United States
  • Mayo Clinic Health System - PPDS
    La Crosse, Wisconsin 54601, United States
  • Sanatorio 9 de Julio SA
    San Miguel de Tucumán, Tucumán T4000DGI, Argentina
  • Fundación Favaloro
    Buenos Aires, C1093AAS, Argentina
  • Hospital Privado Centro Médico de Córdoba
    Córdoba, Argentina
  • UZ Gent
    Gent, Oost-Vlaanderen 9000, Belgium
  • UZ Gasthuisberg
    Leuven, Vlaams Brabant 3000, Belgium
  • AZ Groeninge
    Kortrijk, West-Vlaanderen 8500, Belgium
  • CHU Mouscron
    Mouscron, 7700, Belgium
  • Clinical Center Banja Luka
    Banja Luka, 78000, Bosnia and Herzegovina
  • Second Multiprofile Hospital for Active Treatment Sofia
    Sofia, Sofia-Grad 1202, Bulgaria
  • Diagnostic and Consulting Center Aleksandrovska EOOD
    Sofia, Sofia-Grad 1431, Bulgaria
  • University Multiprofile Hospital for Active Treatment Sveta Anna
    Sofia, Sofia-Grad 1750, Bulgaria
  • Acibadem City Clinic University Multiprofile Hospital for Active Treatment EOOD
    Sofia, Sofia-Grad 1784, Bulgaria
  • University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski EAD
    Pleven, 5800, Bulgaria
  • Multiprofile Hospital for Active Treatment Eurohospital
    Plovdiv, 4004, Bulgaria
  • Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases Dr.D.Gramatikov- Ruse- PPDS
    Ruse, 7002, Bulgaria
  • Medical Center-1-Sevlievo EOOD
    Sevlievo, 5400, Bulgaria
  • Medical Center Excelsior OOD - PPDS
    Sofia, 1000, Bulgaria
  • University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD
    Sofia, 1431, Bulgaria
  • University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna - ISUL EAD
    Sofia, 1527, Bulgaria
  • Medical Center Convex EOOD
    Sofia, 1680, Bulgaria
  • Diagnostic Consultative Centre Mladost - M OOD
    Varna, 9000, Bulgaria
  • Percuro Clinical Research LTD
    Victoria, British Columbia V8P 2P5, Canada
  • Toronto Digestive Disease Associates Inc
    Toronto, Ontario M3N 2V7, Canada
  • Hospital Pablo Tobón Uribe
    Medellin, Antioquia 050034, Colombia
  • Fundación Clínica Shaio
    Bogota, Cundinamarca 111121, Colombia
  • Servimed S.A.S
    Bucaramanga, Santander 680003, Colombia
  • IPS Centro Médico Julián Coronel S.A.S. - PPDS
    Cali, Colombia
  • East Viru Central Hospital
    Kohta-Järve, 31025, Estonia
  • OÜ LV Venter
    Parnu, 80010, Estonia
  • West Tallinn Central Hospital
    Tallinn, 10617, Estonia
  • Ippokrateio General Hospital of Athens
    Athens, Attiki 11527, Greece
  • University General Hospital of Patras
    Patras, 26504, Greece
  • Theageneio Anticancer Oncology Hospital of Thessaloniki
    Thessaloniki, 54007, Greece
  • Euromedica - PPDS
    Thessaloniki, 54645, Greece
  • Bekes Megyei Kozponti Korhaz
    Bekescsaba, 5600, Hungary
  • Magyar Honvédség Egészségügyi Központ
    Budapest, 1062, Hungary
  • Pannónia Magánorvosi Centrum Kft
    Budapest, 1136, Hungary
  • ENDOMEDIX Kft.
    Budapest, 1139, Hungary

Showing the first 100 of 207 sites across 22 countries.

08

References and documents

Study documents

  • Study protocol · Nov 11, 2019
  • Statistical analysis plan · Nov 4, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03259308
Lead sponsor
Shire
Responsible party
Sponsor
First posted
Aug 23, 2017
Start date
Dec 5, 2017
Primary completion
Jul 15, 2020
Completion
Oct 6, 2020
Results posted
Apr 26, 2021
Last update
Apr 26, 2021

Study contacts

Study Director
study director · Shire

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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