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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01387594
First received: June 30, 2011
Last updated: April 13, 2017
Last verified: April 2017
  Purpose
Study is designed to show a lack of effect on white blood cells circulating in the spinal fluid.

Condition Intervention Phase
Crohn's Disease
Ileitis
Ileo-colonic and Colonic Crohn's Disease
Granulomatous Colitis
Regional Enteritis
Ulcerative Colitis
Procedure: lumbar puncture
Drug: lumbar puncture
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Basic Science
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)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 49
Study Start Date: May 2012
Study Completion Date: November 2015
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Interventions prior to treatment. Control arm
Procedure: lumbar puncture
2 lumbar punctures prior to treatment; study drug 225mg SC once a month X 3 doses.
Experimental: Cohort 2
Interventions prior to and after 3 monthly injections
Drug: lumbar puncture
1 lumbar puncture before and after 3 doses; study drug 225mg SC once a month X 3 doses.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01387594

Locations
Austria
AKH Wien Universitaetsklinik fuer Innere Medizin III Klinische Abteilung fuer Gastroenterologie und
Wien, Austria, 1090
Belgium
Hopital Erasme
Brussels, Belgium, B-1000
UZ Gasthuisberg
Leuven, Belgium, B-3000
France
Hopital Cardiologique
Lille Cedex, France, 59037
Hopital Huriez, CHRU de Lille
Lille Cedex, France, 59037
Hopital Saint-Louis - CIC
Paris, France, 75010
Hopital Saint-Louis
Paris, France, 75010
Germany
Charité, Universitaetsmedizin Berlin, Campus Virchow Klinikum,
Berlin, Germany, 13353
Netherlands
Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
Amsterdam, Netherlands, 1105 AZ
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01387594     History of Changes
Other Study ID Numbers: A7281008
2011-001443-74 ( EudraCT Number )
Study First Received: June 30, 2011
Results First Received: November 15, 2016
Last Updated: April 13, 2017

Keywords provided by Pfizer:
Crohn's disease lumbar puncture anti-MAdCAM monoclonal antibody PF-00547659 Ulcerative Colitis

Additional relevant MeSH terms:
Crohn Disease
Colitis
Ulcer
Colitis, Ulcerative
Enteritis
Ileitis
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Colonic Diseases
Pathologic Processes
Ileal Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 27, 2017