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

Ulcerative Colitis Clinical Trial

— TOSCA  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01387594
• Other study ID #: A7281008
• Secondary ID: 2011-001443-74
• Status: Completed
• Phase: Phase 1
• Start date: May 3, 2012
• Est. completion date: November 26, 2015

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: November 26, 2015
• Est. primary completion date: March 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

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

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

Locations

Country	Name	City	State
Austria	AKH Wien Universitaetsklinik fuer Innere Medizin III Klinische Abteilung fuer Gastroenterologie und	Wien
Belgium	Hopital Erasme	Brussels
Belgium	UZ Gasthuisberg	Leuven
France	Hopital Cardiologique	Lille Cedex
France	Hopital Huriez, CHRU de Lille	Lille Cedex
France	Hopital Saint-Louis	Paris
France	Hopital Saint-Louis - CIC	Paris
Germany	Charité, Universitaetsmedizin Berlin, Campus Virchow Klinikum,	Berlin
Netherlands	Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline
Primary	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.	Baseline, Month 3
Secondary	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.	Baseline up to Week 12
Secondary	Cohorts 1 and 2: Number of Participants Who Developed Anti-Drug Antibodies (ADAs) to PF-00547659	Serum samples were analysed for presence of ADAs to PF-00547659. Participants who showed positive results for PF-00547659 were reported.	Day 1; Weeks 4, 8, 9-11 (Cohort 2 only), 12, 20, 28, and 36; Early Withdrawal
Secondary	Cohorts 1 and 2: Number of Participants With Injection Site Reactions by Severity	Injection site reaction AEs include: injection site irritation, injection site pain, injection site rash, contusion, and erythema.	Baseline till End of Study/Early Withdrawal, up to Week 12

External Links

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