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)

• ClinicalTrials.gov Identifier: NCT01387594
• Recruitment Status: Completed
• First Posted: July 4, 2011
• Results First Posted: April 26, 2017
• Last Update Posted: June 3, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• 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)
• Actual Study Start Date: May 3, 2012
• Actual Primary Completion Date: March 31, 2014
• Actual Study Completion Date: November 26, 2015

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

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 Outcome Measures :

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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• 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

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

Shire

Investigators

• Study Director: Study Director; Takeda

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Stüve 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.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01387594
• Other Study ID Numbers: A7281008; 2011-001443-74 ( EudraCT Number )
• First Posted: July 4, 2011
• Results First Posted: April 26, 2017
• Last Update Posted: June 3, 2021
• Last Verified: May 2021

Keywords provided by Takeda ( Shire ):

Crohn's disease lumbar puncture anti-MAdCAM monoclonal antibody PF-00547659 Ulcerative Colitis

Additional relevant MeSH terms:

Crohn Disease; Colitis; Colitis, Ulcerative; Enteritis; Ileitis; Ulcer; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colonic Diseases; Pathologic Processes; Ileal Diseases