A Study to Evaluate the Efficacy and Safety of PF-06480605 in Adults With Moderate to Severe Ulcerative Colitis
Phase 2
Completed
- Conditions
- Moderate to Severe Ulcerative Colitis
- Interventions
- Drug: Induction- PF-06480605 450 mg SC Q4WOther: Induction- Placebo SC Q4WDrug: Induction- PF-06480605 50 mg SC Q4WDrug: Induction- PF-06480605 150 mg SC Q4WDrug: Chronic- PF-06480605 50 mg SC Q4WDrug: Chronic- PF-06480605 150 mg SC Q4WDrug: Chronic- PF-06480605 450 mg SC Q4W
- Registration Number
- NCT04090411
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This phase 2b study is designed to have all subjects go into a 12 week induction period to compare different doses of study drug against placebo. After induction is complete all subjects will receive active therapy for 40 weeks, followed by a 12 week follow up period.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 246
Inclusion Criteria
-
A diagnosis of UC for ≥3 months.
-
Participants with moderate to severe active UC as defined by a Total Mayo Score of
≥6, and an endoscopic subscore of ≥2.
-
Active disease beyond the rectum (>15 cm of active disease from the anal verge at the screening endoscopy).
-
Must have failed or been intolerant to at least one of the following class of medications: steroids, immunosuppressants, anti-TNFs, anti-integrin inhibitors, anti- IL-12/23 inhibitors, or JAK inhibitors.
Exclusion Criteria
- Participants with a diagnosis of ischemic colitis, infectious colitis, radiation colitis, microscopic colitis, indeterminate colitis, or findings suggestive of Crohn's disease (eg, skip lesions, fistulae/perianal disease, non-necrotizing granulomas, etc.).
- Participants with an imminent need for surgery or with elective surgery scheduled to occur during the study
- Chest Radiograph showing abnormalities: The study will accept a Chest x-ray or computed tomography scan of the chest examination performed up to 12 weeks prior to screening if available.
- 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
- Infected with tuberculosis, (TB): Any evidence of untreated latent or active TB infection.
- Infected with human immunodeficiency virus, (HIV), Hepatitis B or C viruses
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 9 Induction- PF-06480605 450 mg SC Q4W Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 450 mg SC Q4W Cohort 1 Induction- Placebo SC Q4W Induction - Placebo SC Q4W, (sub-cutaneous every 4 weeks) Chronic- PF-06480605 50 mg SC Q4W Cohort 1 Chronic- PF-06480605 50 mg SC Q4W Induction - Placebo SC Q4W, (sub-cutaneous every 4 weeks) Chronic- PF-06480605 50 mg SC Q4W Cohort 2 Induction- Placebo SC Q4W Induction - Placebo SC Q4W, Chronic- PF-06480605 150 mg SC Q4W Cohort 2 Chronic- PF-06480605 150 mg SC Q4W Induction - Placebo SC Q4W, Chronic- PF-06480605 150 mg SC Q4W Cohort 3 Induction- Placebo SC Q4W Induction - Placebo SC Q4W, Chronic- PF-06480605 450 mg SC Q4W Cohort 3 Chronic- PF-06480605 450 mg SC Q4W Induction - Placebo SC Q4W, Chronic- PF-06480605 450 mg SC Q4W Cohort 4 Induction- PF-06480605 50 mg SC Q4W Induction- PF-06480605 50 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W Cohort 4 Chronic- PF-06480605 50 mg SC Q4W Induction- PF-06480605 50 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W Cohort 5 Induction- PF-06480605 150 mg SC Q4W Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W Cohort 5 Chronic- PF-06480605 50 mg SC Q4W Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W Cohort 6 Induction- PF-06480605 150 mg SC Q4W Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W Cohort 6 Chronic- PF-06480605 150 mg SC Q4W Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W Cohort 7 Induction- PF-06480605 450 mg SC Q4W Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W Cohort 7 Chronic- PF-06480605 50 mg SC Q4W Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W Cohort 8 Induction- PF-06480605 450 mg SC Q4W Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W Cohort 8 Chronic- PF-06480605 150 mg SC Q4W Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W Cohort 9 Chronic- PF-06480605 450 mg SC Q4W Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 450 mg SC Q4W
- Primary Outcome Measures
Name Time Method Proportion of participants achieving clinical remission (defined as a Total Mayo Score ≤2, with no individual subscore >1) at Week 14. Safety and tolerability will also be assessed week 0-14 Incidence of serious adverse events (SAEs) during the induction period. week 0-14 Incidence of clinically significant abnormalities in vital signs, electrocaridograms, (ECGs) and laboratory values during the induction period. week 0-14 Incidence of AEs or SAEs leading to discontinuation during the chronic therapy period. Weeks 14-64 Incidence and severity of treatment emergent adverse events (TEAEs) during the induction period. week 0-14 Incidence and severity of treatment emergent adverse events (TEAEs) during the chronic therapy period. Weeks 14-64 Incidence of AEs or SAEs leading to discontinuation during the induction period. week 0-14 Incidence of serious adverse events (SAEs) during the chronic therapy period. Weeks 14-64 Incidence of clinically significant abnormalities in vital signs, ECGs and laboratory values during the chronic therapy period. Weeks 14-64
- Secondary Outcome Measures
Name Time Method Proportion of participants achieving remission Food and Drug Administration, ((FDA) definition 1 - defined as endoscopic subscore = 0 or 1, stool frequency subscore = 0, and rectal bleeding subscore = 0) at Week 14. week 0-14 Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 14. week 0-14 Proportion of participants achieving endoscopic remission (defined as endoscopic subscore = 0) at Week 14. week 0-14 Proportion of participants achieving remission (FDA definition 2 - defined as endoscopic subscore = 0 or 1, ≥1 point decrease from baseline to achieve a stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0) at Week 14. week 0-14 PF 06480605 trough concentrations during the induction period through Week 14. week 0-14 Change from baseline in fecal calprotectin during the induction period through Week 14. week 0-14 Change from baseline in hsCRP during the induction period through Week 14. week 0-14 Change from baseline in serum sTL1A during the induction period through Week 14. week 0-14 Proportion of participants achieving sustained remission-FDA definition 1 (ie, remission-FDA definition 1 at both Week 14 and Week 56). Weeks 14-56 Proportion of participants achieving sustained remission-FDA definition 2 (ie, remission-FDA definition 2 at both Week 14 and Week 56). Weeks 14-56 Incidence of development of anti drug antibodies (ADAs) and neutralizing antibodies (NAbs) during the induction period through Week 14. week 0-14 Proportion of participants achieving clinical remission (defined as a Total Mayo Score >/= to 2, with no individual subscore >1) at Week 56. Weeks 14-56 Proportion of participants achieving sustained clinical remission (ie, clinical remission at both Week 14 and Week 56). Weeks 14-56 Proportion of participants achieving remission (FDA definition 1 - defined as endoscopic subscore = 0 or 1, stool frequency subscore = 0, and rectal bleeding subscore = 0) at Week 56. Weeks 14-56 Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 56. Weeks 14-56 Proportion of participants achieving sustained endoscopic improvement (ie, endoscopic improvement at both Week 14 and Week 56). Weeks 14-56 Proportion of participants achieving endoscopic remission (defined as endoscopic sub-score = 0) at Week 56. Weeks 14-56 PF-06480605 concentration from Week 14 through the End of Study Visit. Weeks 14-64 Change from week 14 in serum sTL1A during the chronic therapy period through the End of Study Visit. Weeks 14-64 Proportion of participants achieving sustained endoscopic remission (ie, endoscopic remission at both Week 14 and Week 56). Weeks 14-56 Change from baseline through the End of the Study Visit in hsCRP. Weeks 14-64 Change from Week 14 in fecal calprotectin during the chronic therapy period through the End of Study Visit Weeks 14-64 Change from Week 14 in hsCRP during the chronic therapy period through the End of Study Visit. Weeks 14-64 Change from baseline through the End of the Study Visit in fecal calprotectin weeks 14-64 Incidence of development of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) from Week 14 through the End of Study Visit. Weeks 14-64 Change from baseline through the End of Study Visit in serum sTL1A. Weeks 14-64
Trial Locations
- Locations (164)
Digestive Health Specialists
🇺🇸Dothan, Alabama, United States
Dothan Surgery Center
🇺🇸Dothan, Alabama, United States
Flowers Hospital
🇺🇸Dothan, Alabama, United States
Lynn Institute of the Ozarks
🇺🇸Little Rock, Arkansas, United States
Surinder Saini, M.D., Inc.
🇺🇸Newport Beach, California, United States
Endoscopy Center of Connecticut, LLC
🇺🇸Hamden, Connecticut, United States
Medical Research Center Of Connecticut, LLC
🇺🇸Hamden, Connecticut, United States
PACT Gastroenterology Center
🇺🇸Hamden, Connecticut, United States
Whitney Imaging
🇺🇸Hamden, Connecticut, United States
Medycal Research Inc.
🇺🇸Brooksville, Florida, United States
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