A Phase 3 interventional study of Ontamalimab and Placebo in Ulcerative Colitis, sponsored by Shire. Completed at 401 sites in 37 countries. Open to participants aged 16 Years to 81 Years. Per ClinicalTrials.gov, last updated 2022-01-14.
Sponsored by Shire · Phase 3, Interventional, and Treatment
The purpose of this study is to evaluate the efficacy of ontamalimab as maintenance therapy treatment of remission, based on composite score of patient-reported symptoms and centrally read endoscopy, in participants with moderate to severe ulcerative colitis (UC).
Participants must have achieved clinical response in induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]). Clinical response is defined as:
i) A decrease from the induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]) 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 OR ii) A decrease from the induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]) baseline in total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding sub score of at least 1 point or an absolute rectal bleeding sub score of 0 or 1.
For eligibility assessment, clinical response will be determined based on the centrally read endoscopy performed during screening and at Week 12 of induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]).
Exclusion Criteria:
Participants will receive 25 milligram (mg) of ontamalimab or placebo and achieved a clinical response in one of the induction studies (SHP647-301 \[NCT03259334\] and SHP647-302 \[NCT03259308\]) will receive 25 mg of ontamalimab as maintenance treatment subcutaneously using a prefilled syringe once in every 4 weeks (Q4W) up to Week 52.
Drug: Ontamalimab
Participants will receive 75 mg of ontamalimab or placebo and achieved a clinical response in one of the induction studies (SHP647-301 \[NCT03259334\] and SHP647-302 \[NCT03259308\]) will receive 75 mg of ontamalimab as maintenance treatment subcutaneously using a prefilled syringe Q4W up to Week 52.
Drug: Ontamalimab
Participants will receive 25 mg or 75 mg ontamalimab or placebo matched to ontamalimab in the induction studies (SHP647-301 \[NCT03259334\] and SHP647-302 \[NCT03259308\]) will receive placebo matched to ontamalimab as maintenance treatment subcutaneously using a prefilled syringe Q4W up to Week 52.
Other: Placebo
Participants will receive 1 milliliter (mL) of ontamalimab sterile aqueous buffered solution at an appropriate oncentration to provide an intended dose of drug (25 or 75 mg).
Also known as: PF-00547659, SHP647
Participants will receive 1 mL of sterile aqueous buffered solution.
Number of Participants With Remission Based on Composite Score at Week 52
Remission: a composite score of participant reported symptoms using daily e-diary and centrally read endoscopy as follows: stool frequency sub-score 0 or 1 with at least a 1-point change from induction study baseline; and rectal bleeding sub-score of 0; and endoscopic sub-score 0 or 1 (modified, excludes friability). The composite score was a recommended measure consisted of Mayo score without the Physician global assessment (PGA) sub-score and ranges from 0-9 points. The Mayo score was a measure of UC disease activity ranged from 0-12 points and consisted of 4 sub-scores, each graded from 0-3 with higher scores indicating more severe disease. Sub-scores were rectal bleeding (range: 0-3, where 0= no blood \& 3=blood alone passes), stool frequency (range: 0-3, where 0= normal number of stools and 3=at least 5 stools more than normal), PGA sub-score (range: 0-3- higher score= severe disease), and an endoscopic sub-score (range: 0-3, where 0= normal/inactive disease; 3= severe disease).
Time frame: At Week 52
Number of Participants With Endoscopic Remission at Week 52
Endoscopic remission was defined by centrally read endoscopic sub-score 0 or 1 (modified, excludes friability). The centrally read endoscopic sub-score of mayo score ranged from 0 to 3, where 0=normal or inactive disease; 3=severe disease (spontaneous bleeding, ulceration).
Time frame: At Week 52
Number of Participants With Clinical Remission at Week 52
Clinical remission was defined by stool frequency sub-score of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency sub-score, and 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 Week 52
Number of Participants With Sustained Remission at Week 52
Sustained remission was defined as in remission at Week 52 visit, among participants who were in remission at the time of baseline. Remission was defined as a stool frequency sub-score of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency sub-score and rectal bleeding sub-score of 0 and endoscopic sub-score of 0 or 1 (modified, excludes friability). Sub-scores were rectal bleeding (range: 0-3, where 0= no blood \& 3=blood alone passes), stool frequency (range: 0-3, where 0= normal number of stools and 3=at least 5 stools more than normal), and an endoscopic sub-score (range: 0-3, where 0= normal/inactive disease; 3= severe disease).
Time frame: At Week 52
Number of Participants With Clinical Response Based on Composite Score at Week 52
Clinical response was defined as a decrease from induction study baseline in the composite score of subject reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30%, with an accompanying decrease in the sub-score for rectal bleeding \>=1 point or a sub-score for rectal bleeding \<= 1. Composite score consisted of Mayo score without the PGA sub-score and ranges from 0 to 9 points. Mayo score was a measure of UC disease activity, ranged from 0 -12 points and consisted of 4 sub-scores, each graded from 0 -3, higher scores indicating more severe disease. The rectal bleeding sub-scores ranges from 0-3, where 0= no blood \& 3=blood alone passes and centrally read endoscopic sub-score ranges from 0-3, where 0= normal/inactive disease; 3= severe disease.
Time frame: At Week 52
Number of Participants With Mucosal Healing Based on Endoscopic and Histologic Assessment at Week 52
Mucosal healing was defined by centrally read endoscopic sub-score 0 or 1 (modified, excludes friability) and centrally read Geboes score of \<=2. The centrally read endoscopic sub-score of mayo score ranges 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 = 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 indicates more severe disease.
Time frame: At Week 52
Number of Participants With Glucocorticoid-free Clinical Remission at Week 52
Glucocorticoid-free clinical remission was defined as clinical remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit among participants using glucocorticoids at the baseline. Clinical remission was defined as stool frequency sub-score of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency sub-score, and rectal bleeding sub-score of 0, at the Week 52 visit. The stool frequency sub-score ranges from 0-3, where 0= normal number of stools and 3=at least 5 stools more than normal and rectal bleeding sub-score ranges from 0-3, where 0= no blood \& 3=blood alone passes).
Time frame: At Week 52
Number of Participants With Glucocorticoid-free Remission at Week 52
Glucocorticoid-free remission was defined as remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit, among participants using glucocorticoids at the baseline. Remission was defined as a composite score of participant-reported symptoms using daily e-diary and endoscopy, with stool frequency sub-score of 0 or 1 with at least a 1-point change from induction study baseline, and rectal bleeding sub-score of 0, and endoscopic sub-score of 0 or 1 (modified, excludes friability). The composite score was a recommended measure consisting of the Mayo score without the PGA sub-score and ranges from 0 to 9 points. The stool frequency sub-score, rectal bleeding sub-score and endoscopic sub-score of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.
Time frame: At Week 52
Number of Participants With Remission Based on Total Mayo Score at Week 52
Remission defined as a total mayo score of less than or equal to (\<=) 2 with no individual sub-score (stool frequency, rectal bleeding, endoscopy \[modified, excludes friability\], and physician's global assessment) exceeding 1. The total mayo score ranges 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: Sub-scores were rectal bleeding (range: 0 to 3, where 0=no blood seen and 3=blood alone passes), stool frequency (range: 0 to 3, where 0=normal number of stools and 3=at least 5 stools more than normal), PGA sub-score (range: 0 to 3-higher score indicating the severe disease), and an endoscopic sub-score (range: 0 to 3, where 0=normal or inactive disease; 3=severe disease \[spontaneous bleeding, ulceration\].
Time frame: At Week 52
Number of Participants With Clinical Remission Based on Both Rectal Bleeding and Stool Frequency Sub-scores of 0
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 Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Number of Participants With Sustained Endoscopic Remission at Week 52
Sustained endoscopic remission was defined as in endoscopic remission at Week 52 visit among participants who were in endoscopic remission at the time of baseline. Endoscopic remission was defined as a centrally read endoscopic sub-score of 0 or 1 (modified, excludes friability). The centrally read endoscopic sub-score range from 0 to 3, where 0=normal or inactive disease; 3=severe disease.
Time frame: At Week 52
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs with start dates at the time of or following the first exposure to investigational product. Number of participants with TEAEs were reported.
Time frame: From start of study drug administration up to follow-up (Week 64)
Number of Participants Who Developed Positive Antidrug Antibodies to Ontamalimab
Antibody testing was conducted using an electro chemiluminescent signal method. Serum samples was analyzed for presence of antidrug antibodies to ontamalimab. Number of participants who developed positive results for ontamalimab were reported.
Time frame: At Week 12, 24, 36 and 52
This study was conducted at 400 sites from 4 April 2018 (first participant first visit) to 1 July 2021 (last participant last visit). A total of 366 participants were enrolled, randomized and received study treatment.
| Milestone | ONTA 25mg/ Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg | Placebo/Placebo | Placebo/ONTA 25mg | Placebo/ONTA 75mg |
|---|---|---|---|---|---|---|---|
| Started | 73 | 71 | 86 | 82 | 11 | 22 | 21 |
| Completed | 24 | 53 | 30 | 59 | 6 | 19 | 17 |
| Not completed | 49 | 18 | 56 | 23 | 5 | 3 | 4 |
| Withdrew: Adverse event | 5 | 7 | 4 | 1 | 0 | 0 | 0 |
| Withdrew: Death | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 6 | 5 | 9 | 10 | 1 | 2 | 0 |
| Withdrew: Physician decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Site terminated by sponsor | 1 | 0 | 2 | 1 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Protocol deviation | 2 | 0 | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Disease relapse | 32 | 5 | 38 | 7 | 3 | 1 | 4 |
| Withdrew: Other | 3 | 0 | 2 | 2 | 0 | 0 | 0 |
Remission: a composite score of participant reported symptoms using daily e-diary and centrally read endoscopy as follows: stool frequency sub-score 0 or 1 with at least a 1-point change from induction study baseline; and rectal bleeding sub-score of 0; and endoscopic sub-score 0 or 1 (modified, excludes friability). The composite score was a recommended measure consisted of Mayo score without the Physician global assessment (PGA) sub-score and ranges from 0-9 points. The Mayo score was a measure of UC disease activity ranged from 0-12 points and consisted of 4 sub-scores, each graded from 0-3 with higher scores indicating more severe disease. Sub-scores were rectal bleeding (range: 0-3, where 0= no blood \& 3=blood alone passes), stool frequency (range: 0-3, where 0= normal number of stools and 3=at least 5 stools more than normal), PGA sub-score (range: 0-3- higher score= severe disease), and an endoscopic sub-score (range: 0-3, where 0= normal/inactive disease; 3= severe disease).
| Participants | ONTA 25 mg/ Placebo | ONTA 25 mg/ONTA 25 mg | ONTA 75 mg/Placebo | ONTA 75 mg/ONTA 75 mg |
|---|---|---|---|---|
| Number of Participants With Remission Based on Composite Score at Week 52 | 6 | 38 | 11 | 33 |
Endoscopic remission was defined by centrally read endoscopic sub-score 0 or 1 (modified, excludes friability). The centrally read endoscopic sub-score of mayo score ranged from 0 to 3, where 0=normal or inactive disease; 3=severe disease (spontaneous bleeding, ulceration).
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| Number of Participants With Endoscopic Remission at Week 52 | 7 | 40 | 13 | 40 |
Clinical remission was defined by stool frequency sub-score of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency sub-score, and 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.
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| Number of Participants With Clinical Remission at Week 52 | 13 | 48 | 19 | 42 |
Sustained remission was defined as in remission at Week 52 visit, among participants who were in remission at the time of baseline. Remission was defined as a stool frequency sub-score of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency sub-score and rectal bleeding sub-score of 0 and endoscopic sub-score of 0 or 1 (modified, excludes friability). Sub-scores were rectal bleeding (range: 0-3, where 0= no blood \& 3=blood alone passes), stool frequency (range: 0-3, where 0= normal number of stools and 3=at least 5 stools more than normal), and an endoscopic sub-score (range: 0-3, where 0= normal/inactive disease; 3= severe disease).
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| Number of Participants With Sustained Remission at Week 52 | 4 | 23 | 7 | 22 |
Clinical response was defined as a decrease from induction study baseline in the composite score of subject reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30%, with an accompanying decrease in the sub-score for rectal bleeding \>=1 point or a sub-score for rectal bleeding \<= 1. Composite score consisted of Mayo score without the PGA sub-score and ranges from 0 to 9 points. Mayo score was a measure of UC disease activity, ranged from 0 -12 points and consisted of 4 sub-scores, each graded from 0 -3, higher scores indicating more severe disease. The rectal bleeding sub-scores ranges from 0-3, where 0= no blood \& 3=blood alone passes and centrally read endoscopic sub-score ranges from 0-3, where 0= normal/inactive disease; 3= severe disease.
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| Number of Participants With Clinical Response Based on Composite Score at Week 52 | 15 | 49 | 20 | 47 |
Mucosal healing was defined by centrally read endoscopic sub-score 0 or 1 (modified, excludes friability) and centrally read Geboes score of \<=2. The centrally read endoscopic sub-score of mayo score ranges 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 = 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 indicates more severe disease.
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| Number of Participants With Mucosal Healing Based on Endoscopic and Histologic Assessment at Week 52 | 6 | 37 | 11 | 29 |
Glucocorticoid-free clinical remission was defined as clinical remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit among participants using glucocorticoids at the baseline. Clinical remission was defined as stool frequency sub-score of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency sub-score, and rectal bleeding sub-score of 0, at the Week 52 visit. The stool frequency sub-score ranges from 0-3, where 0= normal number of stools and 3=at least 5 stools more than normal and rectal bleeding sub-score ranges from 0-3, where 0= no blood \& 3=blood alone passes).
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| Number of Participants With Glucocorticoid-free Clinical Remission at Week 52 | 1 | 12 | 3 | 12 |
Glucocorticoid-free remission was defined as remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit, among participants using glucocorticoids at the baseline. Remission was defined as a composite score of participant-reported symptoms using daily e-diary and endoscopy, with stool frequency sub-score of 0 or 1 with at least a 1-point change from induction study baseline, and rectal bleeding sub-score of 0, and endoscopic sub-score of 0 or 1 (modified, excludes friability). The composite score was a recommended measure consisting of the Mayo score without the PGA sub-score and ranges from 0 to 9 points. The stool frequency sub-score, rectal bleeding sub-score and endoscopic sub-score of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| Number of Participants With Glucocorticoid-free Remission at Week 52 | 0 | 8 | 2 | 10 |
Remission defined as a total mayo score of less than or equal to (\<=) 2 with no individual sub-score (stool frequency, rectal bleeding, endoscopy \[modified, excludes friability\], and physician's global assessment) exceeding 1. The total mayo score ranges 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: Sub-scores were rectal bleeding (range: 0 to 3, where 0=no blood seen and 3=blood alone passes), stool frequency (range: 0 to 3, where 0=normal number of stools and 3=at least 5 stools more than normal), PGA sub-score (range: 0 to 3-higher score indicating the severe disease), and an endoscopic sub-score (range: 0 to 3, where 0=normal or inactive disease; 3=severe disease \[spontaneous bleeding, ulceration\].
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| Number of Participants With Remission Based on Total Mayo Score at Week 52 | 5 | 38 | 10 | 33 |
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.
| Participants | ONTA 25mg/ Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| At Week 4 | 28 | 25 | 25 | 24 |
| At Week 8 | 22 | 25 | 29 | 31 |
| At Week 12 | 18 | 26 | 22 | 30 |
| At Week 16 | 16 | 32 | 17 | 35 |
| At Week 20 | 20 | 25 | 16 | 31 |
| At Week 24 | 12 | 31 | 12 | 31 |
| At Week 28 | 13 | 31 | 19 | 32 |
| At Week 32 | 17 | 35 | 13 | 30 |
| At Week 36 | 13 | 37 | 13 | 32 |
| At Week 40 | 15 | 34 | 12 | 25 |
| At Week 44 | 11 | 27 | 12 | 33 |
| At Week 48 | 13 | 32 | 16 | 27 |
| At Week 52 | 9 | 33 | 10 | 30 |
Sustained endoscopic remission was defined as in endoscopic remission at Week 52 visit among participants who were in endoscopic remission at the time of baseline. Endoscopic remission was defined as a centrally read endoscopic sub-score of 0 or 1 (modified, excludes friability). The centrally read endoscopic sub-score range from 0 to 3, where 0=normal or inactive disease; 3=severe disease.
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg |
|---|---|---|---|---|
| Number of Participants With Sustained Endoscopic Remission at Week 52 | 4 | 27 | 8 | 29 |
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs with start dates at the time of or following the first exposure to investigational product. Number of participants with TEAEs were reported.
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg | Placebo/Placebo | Placebo/ONTA 25mg | Placebo/ONTA 75mg |
|---|---|---|---|---|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 46 | 41 | 54 | 51 | 8 | 11 | 12 |
Antibody testing was conducted using an electro chemiluminescent signal method. Serum samples was analyzed for presence of antidrug antibodies to ontamalimab. Number of participants who developed positive results for ontamalimab were reported.
| Participants | ONTA 25mg/Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg | Placebo/Placebo | Placebo/ONTA 25mg | Placebo/ONTA 75mg |
|---|---|---|---|---|---|---|---|
| At Week 12 | 7 | 6 | 8 | 4 | 2 | 0 | 4 |
| At Week 24 | 6 | 5 | 5 | 4 | 1 | 0 | 1 |
| At Week 36 | 5 | 3 | 2 | 4 | 2 | 1 | 2 |
| At Week 52 | 1 | 2 | 6 | 4 | 1 | 1 | 1 |
Collected over From start of study drug administration up to Week 64. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ONTA 25mg/ Placebo | 0/73 (0%) | 6/73 (8.2%) | 41/73 (56.2%) |
| ONTA 25mg/ONTA 25mg | 0/71 (0%) | 9/71 (12.7%) | 27/71 (38%) |
| ONTA 75mg/Placebo | 1/86 (1.2%) | 9/86 (10.5%) | 52/86 (60.5%) |
| ONTA 75mg/ONTA 75mg | 0/82 (0%) | 2/82 (2.4%) | 30/82 (36.6%) |
| Placebo/Placebo | 1/11 (9.1%) | 1/11 (9.1%) | 8/11 (72.7%) |
| Placebo/ONTA 25mg | 0/22 (0%) | 0/22 (0%) | 11/22 (50%) |
| Placebo/ONTA 75mg | 0/21 (0%) | 2/21 (9.5%) | 9/21 (42.9%) |
| Event | ONTA 25mg/ Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg | Placebo/Placebo | Placebo/ONTA 25mg | Placebo/ONTA 75mg |
|---|---|---|---|---|---|---|---|
| Myocardial infarctionCardiac disorders | 0/73 | 0/71 | 0/86 | 0/82 | 1/11 | 0/22 | 0/21 |
| Large intestine perforationGastrointestinal disorders | 1/73 | 0/71 | 0/86 | 0/82 | 1/11 | 0/22 | 0/21 |
| PeritonitisInfections and infestations | 1/73 | 0/71 | 0/86 | 0/82 | 1/11 | 0/22 | 0/21 |
| SepsisInfections and infestations | 0/73 | 0/71 | 1/86 | 0/82 | 1/11 | 0/22 | 0/21 |
| Joint injuryInjury, poisoning and procedural complications | 0/73 | 0/71 | 0/86 | 0/82 | 0/11 | 0/22 | 1/21 |
| Uterine polypReproductive system and breast disorders | 0/73 | 0/71 | 0/86 | 0/82 | 0/11 | 0/22 | 1/21 |
| Colitis ulcerativeGastrointestinal disorders | 2/73 | 1/71 | 1/86 | 0/82 | 0/11 | 0/22 | 0/21 |
| Chest discomfortGeneral disorders | 0/73 | 1/71 | 0/86 | 0/82 | 0/11 | 0/22 | 0/21 |
| Drug hypersensitivityImmune system disorders | 0/73 | 1/71 | 0/86 | 0/82 | 0/11 | 0/22 | 0/21 |
| PneumoniaInfections and infestations | 0/73 | 1/71 | 0/86 | 0/82 | 0/11 | 0/22 | 0/21 |
| Event | ONTA 25mg/ Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg | Placebo/Placebo | Placebo/ONTA 25mg | Placebo/ONTA 75mg |
|---|---|---|---|---|---|---|---|
| Colitis ulcerativeGastrointestinal disorders | 17/73 | 3/71 | 29/86 | 6/82 | 4/11 | 0/22 | 1/21 |
| NasopharyngitisInfections and infestations | 4/73 | 3/71 | 3/86 | 6/82 | 2/11 | 1/22 | 1/21 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 4/73 | 4/71 | 3/86 | 3/82 | 0/11 | 1/22 | 3/21 |
| HeadacheNervous system disorders | 4/73 | 3/71 | 0/86 | 3/82 | 1/11 | 3/22 | 1/21 |
| Corona virus infectionInfections and infestations | 0/73 | 0/71 | 1/86 | 0/82 | 1/11 | 1/22 | 2/21 |
| AnaemiaBlood and lymphatic system disorders | 2/73 | 4/71 | 3/86 | 1/82 | 1/11 | 0/22 | 0/21 |
| LeukopeniaBlood and lymphatic system disorders | 0/73 | 0/71 | 1/86 | 1/82 | 1/11 | 0/22 | 0/21 |
| LymphopeniaBlood and lymphatic system disorders | 0/73 | 0/71 | 0/86 | 0/82 | 1/11 | 0/22 | 0/21 |
| ArrhythmiaCardiac disorders | 0/73 | 0/71 | 0/86 | 0/82 | 1/11 | 0/22 | 0/21 |
| Abdominal painGastrointestinal disorders | 3/73 | 2/71 | 4/86 | 3/82 | 1/11 | 0/22 | 0/21 |
The safety set consisted of all participants who had received at least 1 dose of Investigational Product (IP) in this study, regardless of treatment received during the induction studies (SHP647-301 \[NCT03259334\] and SHP647-302 \[NCT03259308\]).
| Age, Continuous(Years) | ONTA 25mg/ Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg | Placebo/Placebo | Placebo/ONTA 25mg | Placebo/ONTA 75mg | Total |
|---|---|---|---|---|---|---|---|---|
| Mean | 43.3 ± 15.40 | 41.2 ± 13.17 | 42.0 ± 13.81 | 42.3 ± 14.21 | 44.7 ± 14.16 | 40.9 ± 9.42 | 39.9 ± 12.10 | 42.1 ± 13.75 |
| Sex: Female, Male(Participants) | ONTA 25mg/ Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg | Placebo/Placebo | Placebo/ONTA 25mg | Placebo/ONTA 75mg | Total |
|---|---|---|---|---|---|---|---|---|
| Female | 27 | 29 | 35 | 35 | 5 | 9 | 10 | 150 |
| Male | 46 | 42 | 51 | 47 | 6 | 13 | 11 | 216 |
| Ethnicity (NIH/OMB)(Participants) | ONTA 25mg/ Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg | Placebo/Placebo | Placebo/ONTA 25mg | Placebo/ONTA 75mg | Total |
|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 6 | 6 | 4 | 7 | 0 | 3 | 1 | 27 |
| Not Hispanic or Latino | 67 | 64 | 82 | 74 | 11 | 19 | 20 | 337 |
| Unknown or Not Reported | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 |
| Race (NIH/OMB)(Participants) | ONTA 25mg/ Placebo | ONTA 25mg/ONTA 25mg | ONTA 75mg/Placebo | ONTA 75mg/ONTA 75mg | Placebo/Placebo | Placebo/ONTA 25mg | Placebo/ONTA 75mg | Total |
|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 4 |
| Asian | 5 | 4 | 5 | 8 | 1 | 2 | 3 | 28 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Black or African American | 3 | 1 | 2 | 2 | 0 | 0 | 1 | 9 |
| White | 58 | 62 | 77 | 69 | 10 | 19 | 17 | 312 |
| More than one race | 4 | 2 | 0 | 0 | 0 | 1 | 0 | 7 |
| Unknown or Not Reported | 0 | 2 | 1 | 2 | 0 | 0 | 0 | 5 |
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