A Study To Evaluate The Safety And Efficacy Of PF-06826647 In Participants With Moderate To Severe Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy and safety of PF-06826647 in moderate to severe ulcerative colitis

Official Title
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A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP, PLACEBO-CONTROLLED STUDY WITH AN OPEN LABEL EXTENSION TO EVALUATE THE SAFETY AND EFFICACY OF PF-06826647 IN PARTICIPANTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: PF-06826647 100 mg QD
* Drug: PF-06826647 300 mg QD
* Drug: PF-06826647 600 mg QD
* Drug: Placebo
* Drug: PF-6826647 400 mg QD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with moderate to severe UC as defined by a total Mayo score of ≥6, with a rectal bleeding subscore of ≥1 and an endoscopic subscore of ≥2; Participants must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for UC: Oral, intravascular, or intramuscular corticosteroids; Immunosuppressants (azathioprine [AZA], 6-MP, or methotrexate [MTX]); Anti-tumor necrosis factor (TNF) inhibitors (eg, infliximab, adalimumab, or golimumab); Anti-integrin inhibitors (eg, vedolizumab); JAK inhibitor (eg, tofacitinib); Anti-IL-12/IL-23 inhibitors (eg, ustekinumab). Exclusion Criteria: Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, and diverticular disease associated with colitis, or Crohn's disease Participants displaying clinical signs of fulminant colitis or toxic megacolon; Participants with evidence of colonic dysplasia, adenomas or neoplasia.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Matched Placebo<br>|
| Experimental: PF-06826647 100 mg once a day (QD)<br>PF-06826647 100 mg once a day (QD) | Drug: PF-06826647 100 mg QD<br>* Investigational Product<br>|
| Experimental: PF-06826647 300 mg QD<br>PF-06826647 300 mg QD | Drug: PF-06826647 300 mg QD<br>* Investigational Product<br>|
| Experimental: PF-06826647 600 mg QD<br>PF-06826647 600 mg QD | Drug: PF-06826647 600 mg QD<br>* Investigational Product<br>|
| Experimental: Open Label Extension, PF-06826647 400 mg QD<br>PF-06826647 400 mg QD | Drug: PF-6826647 400 mg QD<br>* Investigational Product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving endoscopic response | Endoscopic response is defined by Mayo endoscopic index < 2 | At Week 8 | 
| Number of Adverse Events (AEs), Serious Adverse Events (SAEs) based on severity and withdrawals due to adverse events (AEs) |  | At Week 60 | 
| Number of Participants With Clinical Laboratory Abnormalities | Following parameters will be analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, lactate dehydrogenase, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, phosphate, bicarbonate); clinical chemistry (glucose, creatine kinase); immunology (CRP); urinalysis (dipstick [urine specific gravity, decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin], microscopy [urine RBC, WBC, urate crystals, calcium, oxalate, miscellaneous [urine mucus and leucocytes]). | At Week 60 | 
| Percentage of participants with clinically significant changes in Electrocardiogram (ECG) | Clinical significant changes in ECG | At Week 60 | 
| Number of Participants With Categorical changes from baseline in Vital Signs Data | Number of participants with increase from baseline in sitting SBP and DBP of greater than or equal to 30 mmHg at Week 60. | At Week 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving clinical remission | Clinical remission is defined by total Mayo score of ≤ 2 with no individual subscore of > 1 | At Week 8 and 60 | 
| Percentage of participants achieving endoscopic remission | Endoscopic remission is defined as Mayo endoscopic index of 0 | At Week 8 and 60 | 
| Percentage of participants achieving mucosal healing | Mucosal healing is defined as both total Mayo score and histologic index of ≤ 1. | At Week 8 and 60 | 
| Percentage of participants achieving clinical response | Clinical response is defined as a decrease from baseline of at least 3 points in total Mayo score with at least 30% change, accompanied by at least one point decrease or absolute score of 0 or 1 in rectal bleeding subscore. | At Week 8 and 60 | 
| Mean change from baseline in partial Mayo score over time |  | Up to 60 weeks | 
| Change from baseline in total Mayo score |  | At Week 8 and 60 | 
| Number of Adverse Events (AEs), Serious Adverse Events (SAEs) based on severity and withdrawals due to adverse events (AEs) |  | At Week 8 | 
| Number of Participants With Clinical Laboratory Abnormalities | Following parameters will be analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, lactate dehydrogenase, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, phosphate, bicarbonate); clinical chemistry (glucose, creatine kinase); immunology (CRP); urinalysis (dipstick [urine specific gravity, decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin], microscopy [urine RBC, WBC, urate crystals, calcium, oxalate, miscellaneous [urine mucus and leucocytes]). | At Week 8 | 
| Percentage of participants with clinically significant changes in Electrocardiogram (ECG) | Clinically significant changes from baseline in ECG (heart rate, QT, QTc, PR and QRS intervals) | At Week 8 | 
| Number of Participants With Categorical Vital Signs Data | Number of participants with increase from baseline in sitting SBP and DBP of greater than or equal to 30 mmHg at Week 8. | At Week 8 |