A Study To Assess The Efficacy And Safety Of PF-04236921 In Subjects With Crohn's Disease Who Failed Anti-TNF Therapy
- Conditions
- Crohn's Disease
- Interventions
- Drug: PF-04236921 SC injection
- Registration Number
- NCT01287897
- Lead Sponsor
- Pfizer
- Brief Summary
This is a proof of concept study to determine the efficacy and safety of a monoclonal antibody with three doses versus placebo. Subjects will be randomized to a treatment and the dose will be delivered subcutaneously twice, 4 weeks apart. All subjects will have moderate to severe refractory Crohn's Disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 250
- Subjects must have failed or are intolerant to anti TNFs
- hsCRP greater or equal to 5.0 mg/L
- Ulcerations demonstrated by colonoscopy as defined by SES CD assessment performed within 8 weeks of study entry (screening) and able to retrospectively complete the SES-CD or colonoscopy performed during screening
- Pregnant or breastfeeding women
- Crohn's Disease with active fistulae or abscess
- History of diverticulitis or symptomatic diverticulosis
- Abnormality in hematology or chemistry profiles at screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo- SC injection PF-04236921 SC injection - Drug Dose level 1 - SC injection PF-04236921 SC injection - Drug Dose level 2 - SC injection PF-04236921 SC injection -
- Primary Outcome Measures
Name Time Method The Crohn's Disease Activity Index (CDAI)-70 Response Rate at Week 8 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg Baseline and Week 8 CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score greater than or equal to (\>=) 0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).
The CDAI-70 Response Rate at Week 8 in Participants Who Received Placebo and PF-04236921 200 mg Baseline and Week 8 CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 1, that will yield different estimates for placebo for the two different models.
The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg Baseline and Week 12 CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).
The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo and PF-04236921 200 mg Baseline and Week 12 CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 3, that will yield different estimates for placebo for the two different models.
- Secondary Outcome Measures
Name Time Method The CDAI-70 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg Baseline and Weeks 2, 4, 6, and 10 CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 5, that will yield different estimates for placebo for the two different models.
The CDAI-100 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg Baseline and Weeks 2, 4, 6, 8, 10, and 12 CDAI-100 response was defined as a decrease in CDAI score of 100 or greater from baseline. The proportions of participants with CDAI-100 response at Week 12 were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).
The CDAI-100 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg Baseline and Weeks 2, 4, 6, 8, 10, and 12 CDAI-100 response was defined as a decrease in CDAI score of 100 or greater from baseline. The proportions of participants with CDAI-100 response at Week 12 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 9, that will yield different estimates for placebo for the two different models.
The CDAI-70 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg Baseline and Weeks 2, 4, 6, and 10 CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).
The CDAI Remission Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg Baseline and Weeks 2, 4, 6, 8, 10, and 12 CDAI remission rate was defined as an absolute CDAI score less than (\<) 150. The proportions of participants with CDAI remission were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).
The CDAI Remission Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg Baseline and Weeks 2, 4, 6, 8, 10, and 12 CDAI remission rate was defined as an absolute CDAI score \<150. The proportions of participants with CDAI remission were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 7, that will yield different estimates for placebo for the two different models.
Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg Baseline and Weeks 2, 4, 6, 8, 10, and 12 CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit, and higher score indicate more severe disease. The Outcome included a Linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).
Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo and PF-04236921 200 mg Baseline and Weeks 2, 4, 6, 8, 10, and 12 CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit, and higher score indicate more severe disease. The Outcome included a Linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 11, that will yield different estimates for placebo for the two different models.
Percentages of Participants With Confirmed Positive Anti-drug Antibodies (ADAs) At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40 The percentage of participants with confirmed positive ADA was summarized for each treatment arm. ADA positive was defined as ADA titer defined as ADA titer (ie, the reciprocal of the highest dilution that gives a value equivalent to the cut point of the assay) \>= 4.32.
Percentages of Participants With Confirmed Positive Neutralizing Antibodies (NAbs) At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40 The percentage of participants with confirmed positive NAbs was summarized for each treatment arm. Only ADA positive samples were analyzed for Nab. A multi-tiered approach was utilized to detect NAbs. NAb serum samples were screened at tier one, and those found presumptively NAb positive was further tested with the confirmatory assay (tier two). The percentage of subjects with confirmed positive NAbs was summarized for each treatment.
Serum PF-04236921 Concentration Over Time Day 1 (predose), and at Weeks 2, 4 (Day 28, predose), 8, 10, 12, 16, 20, 24, 28, 32, 36, and 40 Number of Participants Who Withdrew From the Study Due to Treatment-emergent Adverse Events (AEs) Induction period: from Week 0 (Day 1) through Week 12; follow-up period: from Week 12 (or discontinuation from the induction period) through last subject visit (up to 28 weeks after completion of or discontinuation from the 12-week induction period) An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. Treatment-emergent were events between first dose of treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Trial Locations
- Locations (190)
UAB Hospital
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Simon Medical Imaging
🇺🇸Scottsdale, Arizona, United States
Digestive Health Research Unit
🇺🇸Scottsdale, Arizona, United States
Adobe Clinical Research, Llc
🇺🇸Tucson, Arizona, United States
Radiology Ltd
🇺🇸Tucson, Arizona, United States
UCSF Endoscopy Unit at Mount Zion
🇺🇸San Francisco, California, United States
University of California - San Francisco
🇺🇸San Francisco, California, United States
University of California San Francisco at Mount Zion
🇺🇸San Francisco, California, United States
Rocky Mountain Clinical Research, LLC
🇺🇸Denver, Colorado, United States
Scroll for more (180 remaining)UAB Hospital🇺🇸Birmingham, Alabama, United States