Clinical Trial: Evaluate PF-00547659 On Cerebrospinal Fluid Lymphocytes In Volunteers With Crohn's Disease Or Ulcerative Colitis Who Failed Or Did Not Tolerate Anti-TNFs

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-Center, Phase 1, Open-Label Evaluation Of The Effect Of PF-00547659 (Anti Madcam Monoclonal Antibody) On Cerebrospinal Fluid (CSF) Lymphocytes In Volunteers With Crohns Disease Or Ulcerative C

Brief Summary: Study is designed to show a lack of effect on white blood cells circulating in the spinal fluid.

Detailed Summary:
Sponsor: Shire

Current Primary Outcome:

• Cohort 2: Baseline Absolute Lymphocyte Count in Cerebrospinal Fluid (CSF) [ Time Frame: Baseline ]
  The primary CSF endpoint of Cohort 2 was the percent change from baseline in absolute lymphocyte counts in CSF after 3 doses of PF-00547659. The hypothesis for the primary endpoint was evaluated using the CSF evaluable population in Cohort 2. CSF samples were obtained via lumbar puncture and analyzed by fluorescence-activated cell sorting (FACS) for total lymphocyte counts. Lumbar punctures were performed by a highly qualified physician using a 20-22 gauge needle, preferably an atraumatic needle.
• Cohort 2: Percent Change From Baseline in Absolute Lymphocyte Count in CSF at Month 3 [ Time Frame: Baseline, Month 3 ]
  The primary CSF endpoint of Cohort 2 was the percent change from baseline in absolute lymphocyte counts in CSF after 3 doses of PF-00547659. The hypothesis for the primary endpoint was evaluated using the CSF evaluable population in Cohort 2. CSF samples were obtained via lumbar puncture and analyzed by FACS for total lymphocyte counts. Lumbar punctures were performed by a highly qualified physician using a 20-22 gauge needle, preferably an atraumatic needle.

Original Primary Outcome: Percent change from baseline (pre treatment) in absolute lymphocyte count in CSF in subjects with CD after receiving 3 monthly doses of PF-00547659 [ Time Frame: Week 9-11 ]

Current Secondary Outcome:

• Cohorts 1 and 2: Total Number of Participants With Non-Lumbar Puncture (LP) Related Treatment-Emergent Adverse Events (AEs), Withdrawals Due to AEs, and Serious Adverse Events (SAEs) During the 12-week Treatment Period [ Time Frame: Baseline up to Week 12 ]
  An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent for this measure are events between first dose of study drug and up to 85 days (Week 12) after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included serious and non-serious AEs.
• Cohorts 1 and 2: Number of Participants Who Developed Anti-Drug Antibodies (ADAs) to PF-00547659 [ Time Frame: Day 1; Weeks 4, 8, 9-11 (Cohort 2 only), 12, 20, 28, and 36; Early Withdrawal ]
  Serum samples were analysed for presence of ADAs to PF-00547659. Participants who showed positive results for PF-00547659 were reported.
• Cohorts 1 and 2: Number of Participants With Injection Site Reactions by Severity [ Time Frame: Baseline till End of Study/Early Withdrawal, up to Week 12 ]
  Injection site reaction AEs include: injection site irritation, injection site pain, injection site rash, contusion, and erythema.

Original Secondary Outcome:

• Frequency of on treatment adverse events, withdrawal due to adverse events, and serious adverse events (SAEs) will be reported [ Time Frame: Week 36 ]
• Proportion of subjects developing anti-drug antibodies (ADA) to PF-00547659 [ Time Frame: Week 36 ]
• Frequency of injection site reactions and other hypersensitivity reactions [ Time Frame: Week 36 ]

Dates:
Date Received: June 30, 2011
Date Started: May 2012
Date Completion:
Last Updated: May 4, 2017
Last Verified: April 2017