Back to resultsEvaluate PF-00547659 On Cerebrospinal Fluid Lymphocytes In Volunteers With Crohn's Disease Or Ulcerative Colitis Who Failed Or Did Not Tolerate Anti-TNFs (TOSCA)
Primary Purpose
Crohn's Disease, Ileitis, Ileo-colonic and Colonic Crohn's Disease
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
lumbar puncture
lumbar puncture
Sponsored by
About this trial
This is an interventional basic science trial for Crohn's Disease focused on measuring Crohn's disease lumbar puncture anti-MAdCAM monoclonal antibody PF-00547659 Ulcerative Colitis
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)
Sites / Locations
- AKH Wien Universitaetsklinik fuer Innere Medizin III Klinische Abteilung fuer Gastroenterologie und
- Hopital Erasme
- UZ Gasthuisberg
- Hopital Cardiologique
- Hopital Huriez, CHRU de Lille
- Hopital Saint-Louis - CIC
- Hopital Saint-Louis
- Charité, Universitaetsmedizin Berlin, Campus Virchow Klinikum,
- Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
Interventions prior to treatment. Control arm
Interventions prior to and after 3 monthly injections
Outcomes
Primary Outcome Measures
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.
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.
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
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
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
Injection site reaction AEs include: injection site irritation, injection site pain, injection site rash, contusion, and erythema.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01387594
Brief Title
Evaluate PF-00547659 On Cerebrospinal Fluid Lymphocytes In Volunteers With Crohn's Disease Or Ulcerative Colitis Who Failed Or Did Not Tolerate Anti-TNFs
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
May 3, 2012 (Actual)
Primary Completion Date
March 31, 2014 (Actual)
Study Completion Date
November 26, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Study is designed to show a lack of effect on white blood cells circulating in the spinal fluid.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Interventions prior to treatment. Control arm
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Interventions prior to and after 3 monthly injections
Intervention Type
Procedure
Intervention Name(s)
lumbar puncture
Intervention Description
2 lumbar punctures prior to treatment; study drug 225mg SC once a month X 3 doses.
Intervention Type
Drug
Intervention Name(s)
lumbar puncture
Intervention Description
1 lumbar puncture before and after 3 doses; study drug 225mg SC once a month X 3 doses.
Primary Outcome Measure Information:
Title
Cohort 2: Baseline Absolute Lymphocyte Count in Cerebrospinal Fluid (CSF)
Description
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.
Time Frame
Baseline
Title
Cohort 2: Percent Change From Baseline in Absolute Lymphocyte Count in CSF at Month 3
Description
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.
Time Frame
Baseline, Month 3
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Baseline up to Week 12
Title
Cohorts 1 and 2: Number of Participants Who Developed Anti-Drug Antibodies (ADAs) to PF-00547659
Description
Serum samples were analysed for presence of ADAs to PF-00547659. Participants who showed positive results for PF-00547659 were reported.
Time Frame
Day 1; Weeks 4, 8, 9-11 (Cohort 2 only), 12, 20, 28, and 36; Early Withdrawal
Title
Cohorts 1 and 2: Number of Participants With Injection Site Reactions by Severity
Description
Injection site reaction AEs include: injection site irritation, injection site pain, injection site rash, contusion, and erythema.
Time Frame
Baseline till End of Study/Early Withdrawal, up to Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
AKH Wien Universitaetsklinik fuer Innere Medizin III Klinische Abteilung fuer Gastroenterologie und
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Hopital Erasme
City
Brussels
ZIP/Postal Code
B-1000
Country
Belgium
Facility Name
UZ Gasthuisberg
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
Hopital Cardiologique
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Hopital Huriez, CHRU de Lille
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Hopital Saint-Louis - CIC
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hopital Saint-Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Charité, Universitaetsmedizin Berlin, Campus Virchow Klinikum,
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
28778448
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.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A7281008&StudyName=A%20Multi-center%2C%20Phase%201%2C%20Open-label%20Evaluation%20Of%20The%20Effect%20Of%20Pf-00547659%20%28anti%20Madcam%20Monoclonal%20Antibody%29%20On%20Cerebrospinal%20Fluid%20%28csf%29%20Lymphocytes%20In%20Volunteers%20With%20Crohns%20Disease%20Or%20Ulcerative%20Colitis%20Who%20Are%20Anti-tnf%20Inadequate%20Responders%20%28tosca%29
Description
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Learn more about this trial
Evaluate PF-00547659 On Cerebrospinal Fluid Lymphocytes In Volunteers With Crohn's Disease Or Ulcerative Colitis Who Failed Or Did Not Tolerate Anti-TNFs
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