Study to Evaluate the Efficacy and Safety of PF-06480605 in Adult Participants With Moderate to Severe Crohn's Disease

Study Overview
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Brief Summary
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This Phase 2a, multicenter, randomized, double-blind, placebo-controlled study examines subcutaneous dose of PF-06480605 150 mg administered every 4 weeks in participants with moderate to severe active Crohn's Disease to characterize safety, efficacy, pharmacokinetics, and immunogenicity

Official Title
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A PHASE 2A, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY WITH AN OPEN LABEL CHRONIC TREATMENT PERIOD TO EVALUATE THE EFFICACY, SAFETY, AND PHARMACOKINETICS OF PF-06480605 IN ADULT PARTICIPANTS WITH MODERATE TO SEVERE CROHN'S DISEASE

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: Investigational Product
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of ileocolonic or colonic CD with at least 3 months or longer prior to the baseline; Central read total SES-CD score of ≥7. For isolated ileal disease, SES-CD total score should be ≥4; An average daily liquid/very soft SF ≥4 or daily AP score ≥2.0; CDAI between 220 and 450 inclusive; Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for CD Exclusion Criteria: Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, diverticular disease, UC, or clinical findings suggestive of UC; Presence of active (draining) fistulae or intra-abdominal or perineal abscesses; Strictures or stenosis with obstructive symptoms; Short bowel syndrome; History of bowel perforation requiring surgical intervention within the past 12 months prior to baseline; Previous bowel surgery resulting in an existing stoma. Participants who have a j-pouch are excluded, as a j-pouch can result in a stoma; History of bowel surgery within 6 months prior to baseline.

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
Interventional Model Description: Participants are assigned to one of two groups in parallel for the duration of the study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group 1<br>PF-06480605 150 mg | Drug: Investigational Product<br>* PF-06480605 150 mg<br>|
| Placebo Comparator: Treatment Group 2<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with endoscopic response 50 | Endoscopy response 50 (SES-CD50) is defined as a reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at least 50% or more. SES-CD score assesses the presence of ulcers, the percentage of ulcerated surface, the percentage of affected surface, and the presence of narrowing using scales ranging from 0 to 3 in each following bowel segment: Ileum, right colon, transverse colon, left colon, rectum. The score ranges from 0 to 60 with higher score indicating more severe disease. | Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with a Crohn's Disease Activity Index (CDAI) clinical remission | Clinical remission is defined as CDAI < 150. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Week 14 | 
| Proportion of participants achieving endoscopic remission | Endoscopic remission is defined as SES-CD < 4 and at least 2-point reduction versus Baseline and no individual subscore > 1 | Week 14 | 
| Proportion of participants achieving endoscopic mucosal healing | Endoscopic mucosal healing defined as complete absence of ulcers in SES-CD | Week 14 | 
| The proportion of participants with Inflammatory Bowel Disease Questioners (IBDQ) total score ≥170 | Inflammatory Bowel Disease Questionnaire (IBDQ) score ranges from 32 to 224. A higher score indicates better quality of life. A score of at least 170 corresponds to clinical remission. | Week 14 | 
| Proportion of participants achieving endoscopic response | Endoscopic response defined as improvement of SES-CD score at least 50% from baseline | Week 52 | 
| Proportion of participants with a CDAI clinical remission | Clinical remission is defined as CDAI < 150. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Week 52 | 
| Proportion of participants achieving endoscopic remission | Endoscopic remission is defined as SES-CD < 4 and at least 2-point reduction versus Baseline and no individual subscore > 1 | Week 52 | 
| Proportion of participants achieving endoscopic mucosal healing | Endoscopic mucosal healing defined as complete absence of ulcers in SES-CD | Week 52 | 
| Proportion of participants with a CDAI clinical remission | CDAI < 150 overtime during induction treatment period | up to week 52 | 
| Proportion of participants with a CDAI clinical response | As defined by a decrease from baseline in CDAI score of at least 100 points or more | Up to week 52 | 
| Proportion of participants achieving Patient Reported Outcome 2 (PRO2) clinical response | PRO2 clinical response is define by improvement in number of liquid/soft stool frequency and abdominal pain score at least 30% from baseline | Up to week 52 | 
| Proportion of participants achieving PRO2 clinical remission | PRO2 clinical remission is defined as SF≤2.5 and AP≤1 | Up to week 52 | 
| Incidence of AEs or SAEs including events leading to withdrawal due to abnormalities in laboratory, vital signs, and ECG. |  | up to week 52 | 
| Incidence of development of severe and serious infections |  | Up to week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn Disease, PF-06480605, SES-CD, CDAI,