TerminatedNCT03259334FIGARO UC 301Updated Jun 14, 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 18 countries. Open to participants aged 16 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-06-14.

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: 380
Allocation: Randomized
Ages: 16 Years to 80 Years
Sex: All

Study summary

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

Conditions studied

Ulcerative Colitis

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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 must be between greater than or equal to (>=)16 and \<=80 years of age at the time of the signing of the informed consent/assent form.
Participants less than (\<) 18 years of age must weigh >=40 kg and must have body mass index (BMI) >=16.5 kilogram per square meter (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:
1. A biopsy report to confirm the histological diagnosis.
2. 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:

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.
Participants >=50 years of age at the time of signing of the informed consent form.
- Participants have had prior treatment with 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, general infections, heart failure, or malignancy.
- Participants with evidence of active or latent infection with Mycobacterium tuberculosis (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 tuberculosis 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.

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.
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 tuberculosis, 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.
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:

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.
A chest x-ray performed within 12 weeks before 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:

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.
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).
Presence of acute coronary syndrome (eg, acute myocardial infarction, unstable angina pectoris) within 24 weeks before screening.
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 hepatitis B virus (HBcAb), the participant would be considered eligible if no presence of HBV DNA is confirmed by HBV DNA polymerasechainreaction(PCR) reflex testing performed in the central laboratory.

Participants with chronic hepatitis C (HCV) (positive HCVAb and HCVRNA). Note: Participants who are HCVAb positive without evidence of HCVRNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCV RNA 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.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels >=3.0×upper limit of normal (ULN).
Total bilirubin level >=1.5×ULN or >2.0×ULN if the participant has a known documented history of Gilbert's syndrome.
Hemoglobin level \<=80 gram per liter (g/L) (8.0 gram per deciliter [g/dL]).
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).
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 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 study.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 380 participants (actual)

Study arms

Experimental
Ontamalimab 25 mg
Participants will receive 25 milligrams (mg) of ontamalimab (SHP647) 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 (SHP647) SC injection using PFS on Week 0, Week 4 and Week 8.
Drug: Ontamalimab
Placebo comparator
Placebo
Participants will receive placebo matched to ontamalimab (SHP647) SC injection using PFS on Week 0, Week 4 and Week 8.
Other: Placebo

Interventions

DrugOntamalimab
Participants will receive 1 mL of SHP647 sterile aqueous buffered solution at an appropriate concentration to provide the intended dose of drug (25 or 75 mg).
Also known as: PF-00547659, SHP647
OtherPlacebo
Participants will receive 1 mL of sterile aqueous buffered solution.

What researchers measure

Primary outcomes

Number of Participants With Remission 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 consisted of 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

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
Number of Participants With Clinical Remission at Week 12
Clinical remission was defined by stool frequency (SF) 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. Rectal bleeding is assessed on a scale from 0-3, where 0: no blood seen, 1: streaks of blood with stool less than half time, 2: obvious blood or streaks of blood with stool most of the time, and 3: blood alone passes. Stool frequency is assessed on a scale from 0-3, where 0: normal number of stools for this participant, 1: 1 to 2 stools more than normal, 2: 3 to 4 stools more than normal, and 3: 5 or more stools more than normal. Higher scores indicated more severe disease.
Time frame: At Week 12
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
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.
Time frame: At Week 12
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. 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
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
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
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
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. Rectal bleeding was assessed on a scale from 0-3, where 0: no blood seen, 1: streaks of blood with stool less than half time, 2: obvious blood or streaks of blood with stool most of the time, and 3: blood alone passes. Stool frequency was assessed on a scale from 0-3, where 0: normal number of stools for this participant, 1: 1 to 2 stools more than normal, 2: 3 to 4 stools more than normal, and 3: 5 or more stools more than normal. Higher scores indicated more severe disease
Time frame: At Weeks 4 and 8
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
Number of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Sub-scores of 0 at Weeks 4, 8, and 12
Clinical remission was defined as both rectal bleeding and stool frequency sub-scores of 0. Rectal bleeding was assessed on a scale from 0-3, where 0: no blood seen, 1: streaks of blood with stool less than half time, 2: obvious blood or streaks of blood with stool most of the time, and 3: blood alone passes. Stool frequency was assessed on a scale from 0-3, where 0: normal number of stools for this participant, 1: 1 to 2 stools more than normal, 2: 3 to 4 stools more than normal, and 3: 5 or more stools more than normal. Higher scores indicated more severe disease.
Time frame: At Weeks 4, 8, and 12
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
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 daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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 the last 10 days prior to 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 e-diary. Higher scores indicating more severe pain.
Time frame: Baseline, Week 12
Change From Baseline in Diarrhea (Average Loose Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12
PRO-UC daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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
Change From Baseline in Average Bowel Movements With Urgency Score Based on PRO-UC Daily e-Diary at Week 12
PRO-UC daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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
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 daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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
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 daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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.
Time frame: Baseline, Week 12
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
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 domains: 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
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 domains: 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
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
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. 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
Number of Participants Based on In-patient Hospitalization
Number of participants based on inpatient hospitalization due to all-cause hospitalization, gastrointestinal related, other illness/problem, and who had undergone gastrointestinal related procedures during the entire study period was reported.
Time frame: Baseline up to Week 12
Median Duration of Total In-patient Days
In-patient 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: Baseline up to Week 12

Results

Posted May 7, 2021

Limitations and caveats

The study was terminated early as per the sponsor decision to discontinue the ontamalimab clinical trial development program for inflammatory bowel diseases (IBD) for reasons unrelated to safety and efficacy.

Participant flow

The study was conducted at 192 sites between 9 February 2018 (first participant first visit) and 23 October 2020 (last participant last visit).

Participant flow — Overall Study
Milestone	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Started	76	153	151
Treated	76	151	151
Completed	66	136	138
Not completed	10	17	13
Withdrew: Adverse event	3	8	5
Withdrew: Withdrawal by subject	4	2	4
Withdrew: Physician decision	1	0	0
Withdrew: Lost to follow-up	0	2	1
Withdrew: Protocol deviation	0	3	2
Withdrew: Lack of efficacy	2	0	1
Withdrew: Randomized but never treated	0	2	0

Outcome measures

PrimaryNumber of Participants With Remission 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 consisted of 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 at Week 12
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Number of Participants With Remission at Week 12	12	28	45

Statistical analysis

Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = 0.617P-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 = 0.018P-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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Number of Participants With Endoscopic Remission at Week 12	16	42	62

Statistical analysis

Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = 0.253P-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 = 0.002P-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 (SF) 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. Rectal bleeding is assessed on a scale from 0-3, where 0: no blood seen, 1: streaks of blood with stool less than half time, 2: obvious blood or streaks of blood with stool most of the time, and 3: blood alone passes. Stool frequency is assessed on a scale from 0-3, where 0: normal number of stools for this participant, 1: 1 to 2 stools more than normal, 2: 3 to 4 stools more than normal, and 3: 5 or more stools more than normal. Higher scores indicated more severe disease.

Time frame:: At Week 12
Reported as:: Count of participants · Participants

Number of Participants With Clinical Remission at Week 12
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Number of Participants With Clinical Remission at Week 12	29	61	76

Statistical analysis

Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = 0.764P-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 = 0.080P-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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Number of Participants With Clinical Response Based on Composite Score at Week 12	34	76	99

Statistical analysis

Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = 0.440P-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 = 0.002P-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.

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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Number of Participants With Mucosal Healing Based on Endoscopic and Histological Assessment Using the Geboes Score Grading System at Week 12	13	35	51

Statistical analysis

Placebo vs Ontamalimab 25 mg · Cochran-Mantel-Haenszel · p = 0.286P-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 = 0.005P-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. 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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Number of Participants With Remission Based on Total Mayo Score at Week 12	11	25	40

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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Number of Participants With Clinical Response Based on Total Mayo Score at Week 12	32	78	97

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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
At Week 4	13	38	47
At Week 8	23	57	62
At Week 12	22	60	78

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

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. Rectal bleeding was assessed on a scale from 0-3, where 0: no blood seen, 1: streaks of blood with stool less than half time, 2: obvious blood or streaks of blood with stool most of the time, and 3: blood alone passes. Stool frequency was assessed on a scale from 0-3, where 0: normal number of stools for this participant, 1: 1 to 2 stools more than normal, 2: 3 to 4 stools more than normal, and 3: 5 or more stools more than normal. Higher scores indicated 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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
At Week 4	15	34	38
At Week 8	23	57	60

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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Number of Participants With Endoscopic Remission With Sub-score of 0 at Week 12	9	10	22

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

Clinical remission was defined as both rectal bleeding and stool frequency sub-scores of 0. Rectal bleeding was assessed on a scale from 0-3, where 0: no blood seen, 1: streaks of blood with stool less than half time, 2: obvious blood or streaks of blood with stool most of the time, and 3: blood alone passes. Stool frequency was assessed on a scale from 0-3, where 0: normal number of stools for this participant, 1: 1 to 2 stools more than normal, 2: 3 to 4 stools more than normal, and 3: 5 or more stools more than normal. Higher scores indicated 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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
At Week 4	7	20	15
At Week 8	12	24	29
At Week 12	11	37	39

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
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Number of Participants With Deep Remission at Week 12	7	6	18

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 daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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 the last 10 days prior to 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 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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 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 ± 0.271	-2.15 ± 0.196	-2.14 ± 0.194

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

PRO-UC daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Change From Baseline in Diarrhea (Average Loose Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12	-2.90 ± 0.378	-3.08 ± 0.273	-3.50 ± 0.272

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

PRO-UC daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Change From Baseline in Average Bowel Movements With Urgency Score Based on PRO-UC Daily e-Diary at Week 12	-2.38 ± 0.341	-2.60 ± 0.246	-2.84 ± 0.245

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 daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 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	-2.27 ± 0.363	-2.78 ± 0.262	-2.86 ± 0.260

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 daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the 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.

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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 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	-2.85 ± 0.337	-3.50 ± 0.242	-3.50 ± 0.240

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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Change From Baseline in Total Sign/Symptom Score Based on PRO-UC Daily e-Diary at Week 12	-1.92 ± 0.234	-2.15 ± 0.169	0.169 ± 0.168

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 domains: 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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
IBDQ Bowel Function Dimension Score: Change at Week 8	11.32 ± 1.414	16.27 ± 1.006	15.70 ± 1.026
IBDQ Bowel Function Dimension Score: Change at Week 12	12.89 ± 1.568	16.19 ± 1.114	17.18 ± 1.127
IBDQ Emotional Status Dimension Score: Change at Week 8	9.15 ± 1.596	14.54 ± 1.136	14.46 ± 1.157
IBDQ Emotional Status Dimension Score: Change at Week 12	10.10 ± 1.732	14.62 ± 1.230	16.01 ± 1.243
IBDQ Systemic Symptoms Dimension Score: Change at Week 8	4.05 ± 0.681	6.47 ± 0.485	6.03 ± 0.494
IBDQ Systemic Symptoms Dimension Score: Change at Week 12	4.44 ± 0.735	6.19 ± 0.522	6.72 ± 0.528
IBDQ Social Function Dimension Score: Change at Week 8	4.89 ± 0.806	7.59 ± 0.576	7.14 ± 0.586
IBDQ Social Function Dimension Score: Change at Week 12	6.11 ± 0.862	7.95 ± 0.615	8.24 ± 0.621

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 domains: 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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Change at Week 8	29.55 ± 4.205	44.97 ± 2.999	43.36 ± 3.053
Change at Week 12	33.52 ± 4.595	45.00 ± 3.269	48.12 ± 3.305

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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Physical Component Summary: Change at Week 12	4.92 ± 0.848	6.76 ± 0.604	6.54 ± 0.610
Mental Component Summary: Change at Week 12	3.89 ± 1.113	5.83 ± 0.792	6.37 ± 0.799

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. 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 Scale	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Physical Functioning: Change at Week 12	4.89 ± 0.766	5.41 ± 0.545	4.32 ± 0.550
Role-Physical: Change at Week 12	3.99 ± 1.059	6.97 ± 0.754	7.65 ± 0.762
Bodily Pain: Change at Week 12	6.28 ± 1.132	8.83 ± 0.805	8.50 ± 0.814
General Health: Change at Week 12	3.36 ± 0.976	4.78 ± 0.693	5.36 ± 0.699
Vitality: Change at Week 12	4.96 ± 1.202	8.08 ± 0.857	8.69 ± 0.865
Social Functioning: Change at Week 12	6.07 ± 1.160	7.80 ± 0.827	8.56 ± 0.833
Role-Emotional: Change at Week 12	3.25 ± 1.082	4.55 ± 0.765	4.04 ± 0.772
Mental Health: Change at Week 12	3.93 ± 1.096	5.81 ± 0.781	6.59 ± 0.786

SecondaryNumber of Participants Based on In-patient Hospitalization

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

Time frame:: Baseline up to Week 12
Reported as:: Count of participants · Participants

Number of Participants Based on In-patient Hospitalization
Participants	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
All-Cause Hospitalization	3	8	5
Gastrointestinal Related	0	5	2
Other Illness/Problem	3	3	3
Undergo Gastrointestinal Related Procedures	0	5	2

SecondaryMedian Duration of Total In-patient Days

In-patient 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:: Baseline up to Week 12
Reported as:: Median · Days

Median Duration of Total In-patient Days
Days	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Median Duration of Total In-patient Days	5.0 (3 to 7)	7.0 (1 to 13)	4.0 (3 to 8)

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
Group	Deaths	Serious	Other
Placebo	0/76 (0%)	5/76 (6.6%)	10/76 (13.2%)
Ontamalimab 25 mg	0/151 (0%)	10/151 (6.6%)	20/151 (13.2%)
Ontamalimab 75 mg	1/151 (0.7%)	8/151 (5.3%)	6/151 (4%)

Most frequent serious events

Showing 10 of 16

Most frequent serious events
Event	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
Colitis ulcerativeGastrointestinal disorders	0/76	6/151	1/151
AnaemiaBlood and lymphatic system disorders	2/76	1/151	0/151
LeukopeniaBlood and lymphatic system disorders	1/76	0/151	0/151
Bursitis infectiveInfections and infestations	1/76	0/151	0/151
Respiratory failureRespiratory, thoracic and mediastinal disorders	1/76	0/151	0/151
Deep vein thrombosisVascular disorders	1/76	0/151	0/151
Myocardial infarctionCardiac disorders	0/76	0/151	1/151
PyrexiaGeneral disorders	0/76	1/151	0/151
Bile duct stoneHepatobiliary disorders	0/76	0/151	1/151
Anal abscessInfections and infestations	0/76	1/151	0/151

Most frequent other events

Most frequent other events
Event	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg
AnaemiaBlood and lymphatic system disorders	7/76	10/151	1/151
NasopharyngitisInfections and infestations	2/76	10/151	3/151
Colitis ulcerativeGastrointestinal disorders	4/76	3/151	2/151

Baseline characteristics

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

Age, Continuous
Age, Continuous(Years)	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg	Total
Mean	38.3 ± 13.33	39.4 ± 13.90	41.2 ± 14.75	39.9 ± 14.14

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg	Total
Female	33	56	62	151
Male	43	95	89	227

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg	Total
Hispanic or Latino	2	2	2	6
Not Hispanic or Latino	74	149	146	369
Unknown or Not Reported	0	0	3	3

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Placebo	Ontamalimab 25 mg	Ontamalimab 75 mg	Total
Race — American Indian or Alaska Native	0	0	0	0
Race — Asian: Japanese	1	6	8	15
Race — Asian: Korean	0	0	0	0
Race — Asian: Other	0	4	1	5
Race — Black or African American	1	2	5	8
Race — White	72	134	136	342
Race — Native Hawaiian or Other Pacific Islander	0	0	0	0
Race — Multiple	2	4	1	7
Race — Other	0	1	0	1

Study locations

207 sites

Atria Clinical Research - Clinedge - PPDS
Little Rock, Arkansas 72209, United States
OM Research LLC - Lancaster - ClinEdge - PPDS
Lancaster, California 93534, United States
Inland Empire Liver Foundation
Rialto, California 92377, United States
Peak Gastroenterology Associates
Colorado Springs, Colorado 80906, United States
Asthma and Allergy Associates PC - CRN - PPDS
Colorado Springs, Colorado 80907, United States
Advanced Clinical Research Network
Coral Gables, Florida 33134, United States
Nuren Medical and Research Center
Miami, Florida 33144, United States
Gastroenterology Group of Naples
Naples, Florida 34102, United States
Omega Research Consultants LLC - Clinedge - PPDS
Orlando, Florida 32810, United States
East Coast Institute for Research, LLC
Saint Augustine, Florida 32086, United States
Gastrointestinal Diseases, Inc. Research
Columbus, Georgia 31904, United States
Northwestern University
Chicago, Illinois 60611, United States
University of Chicago Medical Center
Chicago, Illinois 60637, United States
Medisphere Medical Research Center LLC
Evansville, Indiana 47714, United States
Laporte County Institute For Clinical Research
Michigan City, Indiana 46360, United States
Clinical Trials of SWLA LLC
Lake Charles, Louisiana 70601, United States
Louisiana Research Center LLC
Shreveport, Louisiana 71105, United States
Massachusetts General Hospital
Boston, Massachusetts 02114, United States
Digestive Health Center PA
Ocean Springs, Mississippi 39564, United States
New York Total Medical Care PC
Brooklyn, New York 11215, United States
Piedmont Healthcare
Statesville, North Carolina 28677, United States
Consultants For Clinical Research Inc
Cincinnati, Ohio 45219, United States
Consultants For Clinical Research Inc
Cincinnati, Ohio 45249, United States
Consultants For Clinical Research Inc
Fairfield, Ohio 45014, United States
Allegheny Center For Digestive Health
Pittsburgh, Pennsylvania 15212, United States
Digestive Disease Associates
Wyomissing, Pennsylvania 19610, United States
Gastro One
Germantown, Tennessee 38138, United States
Vanderbilt University Medical Center
Nashville, Tennessee 37232, United States
Advanced Gastroenterology-Union City
Union City, Tennessee 38261, United States
Inquest Clinical Research/Coastal Gastroenterology Associates, PA
Baytown, Texas 77521, United States
Northside Gastroenterology
Cypress, Texas 77429, United States
DM Clinical Research - ERN - PPDS
Tomball, Texas 77375, United States
HP Clinical Research
Bountiful, Utah 84010, United States
Digestive Health Center at UWMC
Seattle, Washington 98195, United States
University of Washington
Seattle, Washington 98195, United States
CHI Franciscan Digestive Care Associates
Tacoma, Washington 98405, United States
Exemplar Research, Inc. - Elkins
Elkins, West Virginia 26241, United States
West Virginia University Hospital
Morgantown, West Virginia 26506, United States
Concord Repatriation General Hospital
Concord, New South Wales 2139, Australia
Liverpool Hospital
Liverpool, New South Wales 2170, Australia
Royal Brisbane & Women's Hospital
Herston, Queensland 4029, Australia
Mater Hospital Brisbane
South Brisbane, Queensland 4101, Australia
Royal Adelaide Hospital
Adelaide, South Australia 5000, Australia
St Vincents Hospital Melbourne - PPDS
Fitzroy, Victoria 3065, Australia
The Alfred Hospital
Melbourne, Victoria 3004, Australia
A.ö. Krankenhaus der Barmherzigen Brüder
St. Veit an der Glan, Kärnten 9300, Austria
LKH-Universitätsklinikum Klinikum Graz
Graz, Steiermark 8036, Austria
Klinikum Klagenfurt Am Woerthersee
Klagenfurt am Wörthersee, 9020, Austria
Salzburger Landeskliniken
Salzburg, 5020, Austria
Universitätsklinikum St. Pölten
St. Pölten, 3100, Austria
Klinikum Wels-Grieskirchen GmbH
Wels, 4600, Austria
Medizinische Universitat Wien (Medical University of Vienna)
Wien, 1090, Austria
Instituto Goiano de Gastroenterologia E Endoscopia Digestiva Ltda
Goiânia, Goiás 74535-170, Brazil
Hospital Da Cidade de Passo Fundo
Passo Fundo, Rio Grande Do Sul 99010-260, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos
Santo André, São Paulo 09190-510, Brazil
University Hospital Center Zagreb
Zagreb, Grad Zagreb 10000, Croatia
Opca Bolnica Karlovac
Karlovac, Karlovacka Županija 47000, Croatia
Opca bolnica Bjelovar
Bjelovar, 43000, Croatia
Clinical Hospital Centre Osijek
Osijek, 31000, Croatia
University Hospital Centre Split
Split, 21000, Croatia
General Hospital Virovitica
Virovitica, 33000, Croatia
General County Hospital Vukovar and Croatian Veterans Hospital
Vukovar, 32000, Croatia
General Hospital Zadar
Zadar, 23 000, Croatia
Hepato-Gastroenterologie HK, s. r. o.
Hradec Kralove, Královéhradecký Kraj 500 12, Czechia
PreventaMed s.r.o.
Olomouc, Olomoucký Kraj 779 00, Czechia
Institut Klinicke A Experimentalni Mediciny
Praha 4, 140 21, Czechia
ISCARE I.V.F. a.s.
Praha 7, 170 04, Czechia
Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z.
Usti nad Labem, 401 13, Czechia
Nemocnice Pardubickeho kraje, a.s. Orlickoustecka nemocnice
Usti nad Orlici, 562 18, Czechia
Universitätsklinikum Ulm
Ulm, Baden-Württemberg 89081, Germany
Universitätsklinikum der RWTH Aachen
Aachen, Nordrhein-Westfalen 52074, Germany
Gastro Campus Research GbR
Münster, Nordrhein-Westfalen 48159, Germany
Universitatsklinikum Schleswig-Holstein
Kiel, Schleswig-Holstein 24105, Germany
Universitätsklinikum Jena
Jena, Thüringen 07747, Germany
Gastroenterologische Facharztpraxis am Mexikoplatz
Berlin-Zehlendorf, 14163, Germany
Charité - Universitätsmedizin Berlin
Berlin, 13353, Germany
Sana Klinikum Biberach
Biberach an der Riss, 88400, Germany
Universitätsklinikum Frankfurt
Frankfurt, 60590, Germany
Asklepios Westklinikum Hamburg Ggmbh
Hamburg, 22559, Germany
Uniklinik Köln
Köln, 50937, Germany
Klinikum rechts der Isa der Technischen Universitaet Muenchen
Munich, 81675, Germany
Shaare Zedek Medical Center
Jerusalem, 91031, Israel
Hadassah Medical Center - PPDS
Jerusalem, 91120, Israel
Galilee Medical Center
Nahariya, 22100, Israel
Nazareth EMMS Hospital
Nazareth, 16100, Israel
Tel Aviv Sourasky Medical Center PPDS
Tel Aviv, 6423906, Israel
Baruch Padeh Poriya Medical Center
Tiberias, 15208, Israel
Azienda Ospedaliera Mater Domini Di Catanzaro
Catanzaro, Calabria 88100, Italy
Azienda Ospedaliero Universitaria Di Modena Policlinico
Modena, Emilia-Romagna 41124, Italy
Azienda Ospedaliera San Camillo Forlanini
Roma, Lazio 00152, Italy
Ospedale Casa Sollievo Della Sofferenza IRCCS
San Giovanni Rotondo (FG), Puglia 71013, Italy
Azienda Ospedaliera Universitaria Careggi
Firenze, Toscana 50134, Italy
Ospedale Sacro Cuore Don Calabria
Negrar, Veneto 37024, Italy
Azienda Ospedale Università Padova - Dipartimento Salute della Donna e del Bambino - INCIPIT - PIN
Padova, Veneto 35128, Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
Bologna, 40138, Italy
A.O.U. Maggiore della Carità
Novara, 28100, Italy
Fondazione IRCCS Policlinico San Matteo di Pavia
Pavia, 27100, Italy
La Sapienza-Università di Roma-Policlinico Umberto I
Roma, 00161, Italy
Fondazione Policlinico Universitario A Gemelli
Roma, 00168, Italy
Istituto Clinico Humanitas
Rozzano (MI), 20089, Italy

Showing the first 100 of 207 sites across 18 countries.

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.

Registry details

Key details

Study ID: NCT03259334
Lead sponsor: Shire
Responsible party: Sponsor
First posted: Aug 23, 2017
Start date: Feb 9, 2018
Primary completion: Jul 22, 2020
Completion: Oct 23, 2020
Results posted: May 7, 2021
Last update: Jun 14, 2021

Study contacts

Study Director

study director · Shire

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

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