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

Phase 1CompletedNCT01387594

Shire49 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Crohn's Disease Ileitis Ileo-colonic and Colonic Crohn's Disease Granulomatous Colitis Regional Enteritis Ulcerative Colitis

Interventions

lumbar puncturePROCEDURE

2 lumbar punctures prior to treatment; study drug 225mg SC once a month X 3 doses.

lumbar punctureDRUG

1 lumbar puncture before and after 3 doses; study drug 225mg SC once a month X 3 doses.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * males and females \>=18 and =\<75 years * For CD subjects: hsCRP \> 5 mg/L and Harvey-Bradshaw Index \> 8 OR when HBI cannot be determined (ie if stoma is present) or hsCRP \< 5mg/L then: active lesions on colonoscopy or flexible sigmoidoscopy or active Crohn's disease on CT or MR enterography * For UC subjects: diagnosis of UC \> 3 months; must have endoscopy to confirm active disease during screening; total mayo score of 6 to 12 points and moderate to severe disease on endoscopy Exclusion Criteria: * Pregnancy or breastfeeding * TB or active enteric infections * Entero vesicular fistulae * Prior use of natalizumab or vedolizumab * Right or left heart failure including symptomatic diastolic dysfunction or unexplained elevation of troponin I (\>0.05 ng/mL)

Locations (9)

AKH Wien Universitaetsklinik fuer Innere Medizin III Klinische Abteilung fuer Gastroenterologie und

Vienna, Austria

Hopital Erasme

Brussels, Belgium

UZ Gasthuisberg

Leuven, Belgium

Hopital Cardiologique

Outcomes

Primary Outcomes

Cohort 2: Baseline Absolute Lymphocyte Count in Cerebrospinal Fluid (CSF)

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.

Time frame: Baseline

Cohort 2: Percent Change From Baseline in Absolute Lymphocyte Count in CSF at 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.

Time frame: Baseline, Month 3

Secondary Outcomes

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

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.

Time frame: Baseline up to Week 12

Data from ClinicalTrials.gov

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