Crohn's DiseasePhase 1TOSCANCT01387594
Evaluate PF-00547659 On Cerebrospinal Fluid Lymphocytes In Volunteers With Crohn's Disease Or Ulcerative Colitis Who Failed Or Did Not Tolerate Anti-TNFs
A Phase 1 study testing lumbar puncture in people with Crohn's Disease and Ileitis, run by Shire at 9 sites in 5 countries.
Trial summary
Study is designed to show a lack of effect on white blood cells circulating in the spinal fluid. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Crohn's Disease, Ileitis, Ileo-colonic and Colonic Crohn's Disease
- What is being tested?
- lumbar puncture
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 9 sitesin 5 countries
- Study dates
- 3 May 2012to 26 Nov 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
France4 sites
Hopital Cardiologique
Lille, 59037
Hopital Huriez, CHRU de Lille
Lille, 59037
Hopital Saint-Louis - CIC
Paris, 75010
Hopital Saint-Louis
Paris, 75010
Austria1 site
AKH Wien Universitaetsklinik fuer Innere Medizin III Klinische Abteilung fuer Gastroenterologie und
Vienna, 1090
Germany1 site
Charité, Universitaetsmedizin Berlin, Campus Virchow Klinikum,
Berlin, 13353
Netherlands1 site
Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
Amsterdam, 1105 AZ
About this study
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 is designed to show a lack of effect on white blood cells circulating in the spinal fluid.
- Conditions
- Crohn's Disease, Ileitis, Ileo-colonic and Colonic Crohn's Disease, Granulomatous Colitis, Regional Enteritis, Ulcerative Colitis
- Being tested
- lumbar puncture
- Keywords
- Crohn's disease lumbar puncture anti-MAdCAM monoclonal antibody PF-00547659 Ulcerative Colitis
- Medical subject headings
- Crohn Disease, Ileitis, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lumbar punctureProcedure or surgery
2 lumbar punctures prior to treatment; study drug 225mg SC once a month X 3 doses.
lumbar punctureDrug
1 lumbar puncture before and after 3 doses; study drug 225mg SC once a month X 3 doses.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Interventions prior to treatment. Control arm Receives: Procedure: lumbar puncture |
| Cohort 2 | Experimental | Interventions prior to and after 3 monthly injections Receives: Drug: lumbar puncture |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
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.
Measured: Baseline, Month 3
Secondary outcomes (3)
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.
Measured: Baseline up to Week 12
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.
Measured: Day 1; Weeks 4, 8, 9-11 (Cohort 2 only), 12, 20, 28, and 36; Early Withdrawal
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.
Measured: Baseline till End of Study/Early Withdrawal, up to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2011 (estimated)
- Study start3 May 2012
- Primary completion31 Mar 2014
- Study completion26 Nov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01387594
- Sponsor's protocol ID
- A7281008
- Other IDs
- 2011-001443-74
- Acronym
- TOSCA
- Status last verified
- May 2021
- First submitted
- 30 Jun 2011
- Last updated
- 3 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 28778448
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01387594
- Acronym / sponsor ID
- TOSCA / A7281008
- Conditions
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 3 May 2012 (actual)
- Primary completion
- 31 Mar 2014 (actual)
- Study completion
- 26 Nov 2015 (actual)
- First posted
- 4 Jul 2011 (estimated)
- Results
- Posted 26 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study is designed to show a lack of effect on white blood cells circulating in the spinal fluid.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Procedure: lumbar punctureInterventions prior to treatment. Control arm |
| Cohort 2 | Experimental | Drug: lumbar punctureInterventions prior to and after 3 monthly injections |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lumbar puncture2 lumbar punctures prior to treatment; study drug 225mg SC once a month X 3 doses. | Procedure or surgery | Cohort 1 |
| lumbar puncture1 lumbar puncture before and after 3 doses; study drug 225mg SC once a month X 3 doses. | Drug | Cohort 2 |
Primary outcome
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.
3 secondary outcomes
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28778448Stuve 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing lumbar puncture in people with Crohn's Disease and Ileitis, run by Shire at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France, Belgium, Austria, Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohort 2: Baseline Absolute Lymphocyte Count in Cerebrospinal Fluid (CSF) (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01387594, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2021.