Clinical trial NCT01387594: Evaluate PF-00547659 On Cerebrospinal Fluid Lymphocytes In Volunteers With Crohn's Disease Or Ulcerative Colitis Who Failed Or Did Not Tolerate Anti-TNFs
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 Colitis Who Are Anti-TNFInadequate Responders (TOSCA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Crohn's Disease
Ileitis
Ileo-colonic and Colonic Crohn's Disease
Granulomatous Colitis
Regional Enteritis
Ulcerative Colitis
Keywords: Crohn's disease lumbar puncture anti-MAdCAM monoclonal antibody PF-00547659 Ulcerative Colitis
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-07-04
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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)

Primary outcomes:
measure: Cohort 2: Baseline Absolute Lymphocyte Count in Cerebrospinal Fluid (CSF)
timeFrame: Baseline
measure: Cohort 2: Percent Change From Baseline in Absolute Lymphocyte Count in CSF at Month 3
timeFrame: Baseline, Month 3
Secondary outcomes:
measure: 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
timeFrame: Baseline up to Week 12
measure: Cohorts 1 and 2: Number of Participants Who Developed Anti-Drug Antibodies (ADAs) to PF-00547659
timeFrame: Day 1; Weeks 4, 8, 9-11 (Cohort 2 only), 12, 20, 28, and 36; Early Withdrawal
measure: Cohorts 1 and 2: Number of Participants With Injection Site Reactions by Severity
timeFrame: Baseline till End of Study/Early Withdrawal, up to Week 12
Other outcomes:
Locations:
city: Wien
country: Austria
facility: AKH Wien Universitaetsklinik fuer Innere Medizin III Klinische Abteilung fuer Gastroenterologie und
city: Brussels
country: Belgium
facility: Hopital Erasme
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Lille Cedex
country: France
facility: Hopital Cardiologique
city: Lille Cedex
country: France
facility: Hopital Huriez, CHRU de Lille
city: Paris
country: France
facility: Hopital Saint-Louis - CIC
city: Paris
country: France
facility: Hopital Saint-Louis
city: Berlin
country: Germany
facility: Charité, Universitaetsmedizin Berlin, Campus Virchow Klinikum,
city: Amsterdam
country: Netherlands
facility: Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Stuve O, Cataldi F, Pradhan V, Gorelick KJ. Normal intrathecal leukocyte cell number and composition do not decrease the incidence of post-lumbar puncture headache. J Neuroimmunol. 2017 Sep 15;310:69-71. doi: 10.1016/j.jneuroim.2017.06.011. Epub 2017 Jun 30.