Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Etrolizumab, RG7413, RO5490261, PRO145223
rhuMAb Beta7 · 8 trials · 3 indications
Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.
Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score.
Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score.
Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Maintenance phase participants were evaluated.
Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. Maintenance phase participants were evaluated.
Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. Clinical Remission is MCS ≤2 with individual subscores ≤1.
The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the Cochran-Mantel-Haenszel test adjusted the difference in remission rates and associated 95% confidence interval for the stratification factors.
The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the Cochran-Mantel-Haenszel test adjusted the difference in remission rates and associated 95% confidence interval for the stratification factors.
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. Remission is MCS ≤2 with individual subscores ≤1 and a rectal bleeding subscore of 0.
| Arm | Type | Description |
|---|---|---|
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 210 mg | EXPERIMENTAL | Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive one subcutaneous (SC) injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. |
| Induction Phase - Cohort 1 (Exploratory): Etrolizumab 105 mg | EXPERIMENTAL | Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. |
| Induction Phase - Cohort 1 (Exploratory): Placebo | PLACEBO_COMPARATOR | Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking. |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 210 mg | EXPERIMENTAL | Cohort 2 is enrolling participants after Cohort 1 and is considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm will receive one SC injection of open-label etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking for the dose of etrolizumab, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. |
| Induction Phase - Cohort 2 (Open-Label): Etrolizumab 105 mg | EXPERIMENTAL | Cohort 2 is enrolling participants after Cohort 1 and is considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm will receive one SC injection of open-label etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 210 mg | EXPERIMENTAL | Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive one SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. |
| Induction Phase - Cohort 3 (Pivotal): Etrolizumab 105 mg | EXPERIMENTAL | Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12. |
| Induction Phase - Cohort 3 (Pivotal): Placebo | PLACEBO_COMPARATOR | Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking. |
| Maintenance Phase - Placebo Responders: Placebo | PLACEBO_COMPARATOR | Participants who received placebo during the Induction Phase (from Cohorts 1 and 3) and achieved a CDAI-70 response at Week 14 will undergo a sham randomization into the Maintenance Phase. Placebo responders from induction will receive blinded maintenance treatment with an SC injection of placebo once every 4 weeks (q4w) from Week 16 to Week 64. |
| Maintenance Phase - Etrolizumab Responders: Placebo | PLACEBO_COMPARATOR | Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64. |
| Maintenance Phase - Etrolizumab Responders: Etrolizumab 105 mg | EXPERIMENTAL | Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64. |
| Etrolizumab + Placebo (IV) | EXPERIMENTAL | Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46. |
| Infliximab + Placebo (Injection) | ACTIVE_COMPARATOR | Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo matching to etrolizumab up to Week 12 and placebo matching to adalimumab up to Week 8. |
| Adalimumab | ACTIVE_COMPARATOR | Participants will receive adalimumab up to Week 8 and placebo matching to etrolizumab up to Week 12. |
| Etrolizumab | EXPERIMENTAL | Participants will receive etrolizumab up to Week 12 and placebo matching to adalimumab up to Week 8. |
| Open-Label Induction Phase: Etrolizumab | EXPERIMENTAL | All participants will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) up to Week 10. |
| Double-Blind Maintenance Phase: Etrolizumab | EXPERIMENTAL | Participants who achieved a clinical response at Week 10 during the induction phase and randomized to this arm for the double-blind maintenance phase will receive etrolizumab 105 mg SC injection Q4W from Week 12 up to Week 62. |
| Double-Blind Maintenance Phase: Placebo | PLACEBO_COMPARATOR | Participants who achieved a clinical response at Week 10 during the induction phase and randomized to this arm for the double-blind maintenance phase will receive placebo (matched to etrolizumab) SC injection Q4W from Week 12 up to Week 62. |
| rhuMAb Beta7 | EXPERIMENTAL | - |
| 1 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Etrolizumab | DRUG | Etrolizumab will be administered as per regimen specified in individual arms. |
| Placebo | DRUG | Etrolizumab-matching placebo will be administered as per regimen specified in individual arms. |
| Infliximab | DRUG | 5 mg/kg of infliximab will be administered by intravenous (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46. |
| Placebo (IV) | OTHER | Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46. |
| Placebo (Injection) | OTHER | Administered by SC injection Q4W until Week 52 |
| Adalimumab | DRUG | Adalimumab 160 milligrams (mg) will be administered subcutaneously (SC) at Week 0; 80 mg SC at Week 2; 40 mg SC at Weeks 4, 6 and 8. |
| Adalimumab Placebo | OTHER | Placebo matching to adalimumab will be administered SC at Weeks 0, 2, 4, 6, and 8. |
| Etrolizumab Placebo | OTHER | Placebo matching to etrolizumab will be administered SC once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]). |
| rhuMAb Beta7 | DRUG | Repeating subcutaneous injection |
Inclusion Criteria: * Moderately to severely active Crohn's Disease (CD) as determined by the CDAI, patient reported outcomes and endoscopically defined disease activity in the ileum and/or colon * Intolerance, refractory disease, or no response to corticosteroids (CS), immunosuppressants (IS), or ...
Top 20 of 23 competitors
rhuMAb Beta7 is an investigational monoclonal antibody being studied for the treatment of moderate to severe ulcerative colitis, a form of inflammatory bowel disease. It has been evaluated in adults aged 18 years and older in clinical trials sponsored by Roche. It is not yet an approved therapy for ulcerative colitis.
rhuMAb Beta7 is being developed by Roche Holding AG, which trades under the ticker RHHBY. Roche sponsored both clinical trials of the drug in ulcerative colitis, including a Phase 1 study and a Phase 2 study conducted across sites in the United States, Europe, Canada, Australia, Israel, and New Zealand.
rhuMAb Beta7 has completed Phase 2 clinical development for ulcerative colitis. Two trials have been completed: a Phase 1 study of 48 patients and a Phase 2 study of 124 patients. No trials are currently listed as active, and the drug is not approved for any indication.
rhuMAb Beta7 has been studied in two completed trials. NCT01336465 was a Phase 2 trial evaluating efficacy and safety in 124 patients with moderate to severe ulcerative colitis. NCT00694980 was a Phase 1 trial assessing safety, pharmacokinetics, pharmacodynamics, and immunogenicity in 48 patients with ulcerative colitis.
The Phase 2 trial NCT01336465 was a randomized, double-blind, placebo-controlled study of rhuMAb Beta7 in 124 adults with moderate to severe ulcerative colitis. It enrolled patients across the United States, Australia, Belgium, Canada, Czechia, Germany, Hungary, Israel, New Zealand, Spain, and the United Kingdom, and has been completed.