A Study to Evaluate the Efficacy and Safety of PF-06480605 in Adults With Moderate to Severe Ulcerative Colitis

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate The Efficacy, Safety, and Pharmacokinetics of PF-06480605 in Adult Participants With Moderate To Severe Ulcerative Colitis

Conditions
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Moderate to Severe Ulcerative Colitis

Intervention / Treatment
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* Drug: Induction- PF-06480605 50 mg SC Q4W
* Drug: Induction- PF-06480605 150 mg SC Q4W
* Drug: Induction- PF-06480605 450 mg SC Q4W
* Other: Induction- Placebo SC Q4W
* Drug: Chronic- PF-06480605 50 mg SC Q4W
* Drug: Chronic- PF-06480605 150 mg SC Q4W
* Drug: Chronic- PF-06480605 450 mg SC Q4W


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Induction - Placebo SC Q4W, (sub-cutaneous every 4 weeks) Chronic- PF-06480605 50 mg SC Q4W | Other: Induction- Placebo SC Q4W<br>* 0 mg Placebo<br>Drug: Chronic- PF-06480605 50 mg SC Q4W<br>* PF-06480605<br>|
| Experimental: Cohort 2<br>Induction - Placebo SC Q4W, Chronic- PF-06480605 150 mg SC Q4W | Other: Induction- Placebo SC Q4W<br>* 0 mg Placebo<br>Drug: Chronic- PF-06480605 150 mg SC Q4W<br>* PF-06480605<br>|
| Experimental: Cohort 3<br>Induction - Placebo SC Q4W, Chronic- PF-06480605 450 mg SC Q4W | Other: Induction- Placebo SC Q4W<br>* 0 mg Placebo<br>Drug: Chronic- PF-06480605 450 mg SC Q4W<br>* PF-06480605<br>|
| Placebo Comparator: Cohort 4<br>Induction- PF-06480605 50 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W | Drug: Induction- PF-06480605 50 mg SC Q4W<br>* PF-06480605<br>Drug: Chronic- PF-06480605 50 mg SC Q4W<br>* PF-06480605<br>|
| Experimental: Cohort 5<br>Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W | Drug: Induction- PF-06480605 150 mg SC Q4W<br>* PF-06480605<br>Drug: Chronic- PF-06480605 50 mg SC Q4W<br>* PF-06480605<br>|
| Experimental: Cohort 6<br>Induction- PF-06480605 150 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W | Drug: Induction- PF-06480605 150 mg SC Q4W<br>* PF-06480605<br>Drug: Chronic- PF-06480605 150 mg SC Q4W<br>* PF-06480605<br>|
| Experimental: Cohort 7<br>Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 50 mg SC Q4W | Drug: Induction- PF-06480605 450 mg SC Q4W<br>* PF-06480605<br>Drug: Chronic- PF-06480605 50 mg SC Q4W<br>* PF-06480605<br>|
| Experimental: Cohort 8<br>Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 150 mg SC Q4W | Drug: Induction- PF-06480605 450 mg SC Q4W<br>* PF-06480605<br>Drug: Chronic- PF-06480605 150 mg SC Q4W<br>* PF-06480605<br>|
| Experimental: Cohort 9<br>Induction- PF-06480605 450 mg SC Q4W, Chronic- PF-06480605 450 mg SC Q4W | Drug: Induction- PF-06480605 450 mg SC Q4W<br>* PF-06480605<br>Drug: Chronic- PF-06480605 450 mg SC Q4W<br>* PF-06480605<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 and severity of treatment emergent adverse events (TEAEs) during the induction period. |  | week 0-14 | 
| Incidence of serious adverse events (SAEs) during the induction period. |  | week 0-14 | 
| Incidence of AEs or SAEs leading to discontinuation 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 and severity of treatment emergent adverse events (TEAEs) during the chronic therapy period. |  | Weeks 14-64 | 
| Incidence of serious adverse events (SAEs) during the chronic therapy period. |  | Weeks 14-64 | 
| Incidence of AEs or SAEs leading to discontinuation 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 
| 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 | 
| 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 | 
| 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 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 | 
| 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 | 
| Proportion of participants achieving sustained endoscopic remission (ie, endoscopic remission at both Week 14 and 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 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 week 14 in serum sTL1A 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 | 
| Change from baseline through the End of the Study Visit in hsCRP. |  | Weeks 14-64 | 
| Change from baseline through the End of Study Visit in serum sTL1A. |  | 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 |