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Completed

NCT Number: 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

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

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Key information

Conditions

Crohn's Disease Colitis Colitis, Ulcerative Colonic Diseases Crohn Disease Digestive System Diseases Enteritis Gastroenteritis Gastrointestinal Diseases Granulomatous Colitis Ileal Diseases Ileitis Ileo-colonic and Colonic Crohn's Disease Inflammatory Bowel Diseases Intestinal Diseases Regional Enteritis Ulcerative Colitis

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

AKH Wien Universitaetsklinik fuer Innere Medizin III Klinische Abteilung fuer Gastroenterologie und, Vienna, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Lumbar Puncture

Procedure

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

lumbar puncture

Drug

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

Primary outcomes

  1. 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.

  2. 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 outcomes

  1. 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.

  2. 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.

  3. 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.

Sponsors and collaborators

Lead sponsor

Shire

Industry

Registry information

Official study 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)

Acronym: TOSCA

Important dates

Study start
2012
Primary completion
2014
Study completion
2015
First posted
Jul 4, 2011
Registry last updated
Jun 3, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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