Study To Test Whether PF-00547659 Is Safe And Improves Disease Symptoms In Patients With Crohn's Disease

Study Overview
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Brief Summary
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Adults with Crohn's disease that is clinically active despite conventional treatment will be eligible for this study. Patients may receive one of three doses of PF-00547659 (experimental drug) or placebo (inactive drug). Disease activity will be measured every two weeks.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-00547659 In Subjects With Crohn's Disease (Opera)

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: PF-00547659 SC injection
* Drug: PF-00547659 SC injection
* Drug: PF-00547659 SC injection
* Drug: PF-00547659 SC injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have failed or are intolerant to anti-TNFs and/or immunosuppressants (AZA, 6-MP, and/or MTX). hsCRP greater than 3mg/L Ulcerations demonstrated by colonoscopy performed during screening or 8 weeks prior to screening Exclusion Criteria: Pregnant or breast feeding Short bowel syndrome due to multiple small bowel resections Presence of a stoma

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-SC Injection<br>Placebo delivered SC, 3 doses separated by 4 weeks. | Drug: PF-00547659 SC injection<br>* Placebo delivered SC, 3 doses separated by 4 weeks<br>|
| Experimental: Drug Dose level 1- SC injection<br>Drug dose level 1 delivered SC, 3 doses separated by 4 weeks. | Drug: PF-00547659 SC injection<br>* Drug dose level 1 delivered SC, 3 doses separated by 4 weeks<br>|
| Experimental: Drug Dose level 2-SC injection<br>Drug dose level 2 delievered SC, 3 doses separated by 4 weeks. | Drug: PF-00547659 SC injection<br>* Drug dose level 2 delivered SC, 3 doses separated by 4 weeks<br>|
| Experimental: Drug Dose level 3- SC injection<br>Drug dose level 3 delivered SC, 3 doses separated by 4 weeks. | Drug: PF-00547659 SC injection<br>* Drug dose level 3 delivered SC, 3 doses separated by 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate | Crohn's Disease Activity Index (CDAI) is a number which consists of information collected from a 7-day diary from the participants regarding symptoms. Remission is considered a score of 150 or less. Active disease is considered 200 or greater. A response to therapy is considered a decline in CDAI score of 70-points from baseline. CDAI response rate at week 8 and week 12 was measured between the investigational product group and the placebo group. | Week 8 and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo | Number of participants with adverse events (AEs), withdrawals due to AEs and Serious AEs (SAEs) were reported. | Week 0-12 | 
| Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo | Number of adverse events (all causalities and treatment related) was reported between the investigational product groups and the placebo group. | Week 0-12 | 
| Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission | Percentage of participants with a CDAI remission (defined as a CDAI reduction to <150 points). | Weeks 8 and week 12 | 
| Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time | Percentage of participants with Crohn's Disease Activity Index (CDAI)-70 response were reported. | Week 2, 4, 6, 8, 10 and 12 | 
| Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer | Percentage of participants with Crohn's Disease Activity Index (CDAI)-100 response were reported. | Week 2, 4, 6, 8, 10 and 12 | 
| Immunogenicity Assessment of Anti-drug Antibodies (ADAs) | Confirmed cumulative incidence of anti-drug antibodies development to PF-00547659 | Day 1, Week 4, Week 8, Week 12, Week 20, Week 28, Week 36 | 
| The Pharmacokinetics (PK) of Total PF-00547659 - Area Under the Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) | The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to area under the concentration-time profile (AUC), clearance (CL) and half life were estimated using data pooled from both typical and additional PK groups. AUCinf is area under the concentration time profile from time zero extrapolated to infinite time. | Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252 | 
| The Pharmacokinetics (PK) of Total PF-00547659 - Area Under the Concentration Time Profile From Time Zero to Time Tau (AUCtau) | The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. AUCtau is area under the concentration time profile from time zero to time tau, the dosing interval, where tau = 672 hours (4 weeks) | Day 1, 14, and 28 | 
| The Pharmacokinetics (PK) of Total PF-00547659 - Maximum Observed Concentration (Cmax) | The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. Cmax is maximum observed concentration. | Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252 | 
| The Pharmacokinetics (PK) of Total PF-00547659 - Time for Cmax (Tmax) | The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. Tmax is time for Cmax. | Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252 | 
| The Pharmacokinetics (PK) of Total PF-00547659 - Terminal Half Life (Thalf) | The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. Thalf is terminal half life. | Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252 | 
| The Pharmacokinetics (PK) of Total PF-00547659 - Apparent Clearance (CL/F) | The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. CL/F is apparent clearance. | Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's disease Safety Efficacy Pharmacokinetics Pharmacodynamics Crohn's Disease Activity Index (CDAI)