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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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21 December 2021 |
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Main ID: |
EUCTR2008-000327-25-PL |
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Date of registration:
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20/05/2008 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED,
PARALLEL-GROUP STUDY OF CE-224,535, AN ANTAGONIST OF THE P2X7
RECEPTOR, IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF
RHEUMATOID ARTHRITIS IN SUBJECTS WHO ARE INADEQUATELY
CONTROLLED ON METHOTREXATE
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Scientific title:
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A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED,
PARALLEL-GROUP STUDY OF CE-224,535, AN ANTAGONIST OF THE P2X7
RECEPTOR, IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF
RHEUMATOID ARTHRITIS IN SUBJECTS WHO ARE INADEQUATELY
CONTROLLED ON METHOTREXATE |
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Date of first enrolment:
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24/06/2008 |
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Target sample size:
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78 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000327-25 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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Czech Republic
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Poland
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Spain
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Key inclusion & exclusion criteria
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Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Any adult at least 18 years of age at Screening;
2. A diagnosis of RA based upon the American College of Rheumatology 1987 Revised
Criteria. The subject has a diagnosis of RA based upon the American College of
Rheumatology, ie, fulfilling at least 4 of the following 7 criteria, for at least 6 consecutive months preceding participation:
• Morning stiffness in and around any joint for more than 1 hour;
• Soft tissue swelling of 3 or more joint areas;
• Swelling of the proximal interphalangeal (PIP), metacarpophalangeal (MCP), or
wrist joints;
• Symmetrical joint swelling;
• Rheumatoid nodules;
• Serum rheumatoid factor positive;
• Radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints;
3. Must have active disease at Screening despite ongoing methotrexate treatment
defined as:
• =4 tender/painful joints on motion (28 joint count);
• =4 swollen joints (28 joint count).
4. Regarding MTX treatment, subjects must comply with all of the following criteria:
• Receiving =7.5 /week (oral or parenteral) for the last 3 months;
• No interruption >2 weeks during the same 3-month period;
• Has received a stable dose for at least 4 weeks prior to Screening; and
• No expected MTX dose change for the 12-week treatment duration.
• Concomitant therapy with folic acid in a minimum of 400 mcg daily (or
equivalent dosing on a less-than daily schedule) or folinic acid once weekly in
locally approved doses (typically 5 mg, 24 hrs after the methotrexate dose).
5. Other permitted DMARDS are: 1) Sulfasalazine at a dosage which has been stable for at least 8 weeks at randomization and does not exceed a total daily dose of 3 grams.
2) Leflunomide at a dosage which has been stable for at least 4 weeks at
randomization and does not exceed 20 mg daily (with the exception of a loading dose of up to 100 mg daily for 3 days at the initiation of therapy). 3) injectable or oral
(auranofin) gold in locally approved doses, stable for at least 8 weeks prior to
randomization 4) d-penicillamine in locally approved doses, stable for at least
8 weeks prior to randomization, 5) chloroquine or hyrdoxychloroquine in locally
approved doses, if it has been at a stable dose for at least 1 year prior to
randomization with no history of anti-malarial related retinal toxicity. NO MORE
THAN 2 OF THESE DMARDS, IN ADDITION TO METHOTREAXTE, MAY BE
GIVEN DURING THE TRIAL OR FOR AT LEAST 1 MONTH PRIOR TO
RANDOMIZATION.
6. Meets ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II,or III
7. Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures; and
8. Must provide written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Exclusion criteria:
1. A diagnosis of any other inflammatory arthritis (eg, spondyloarthropathies) or
secondary, noninflammatory arthritis (eg, osteoarthritis, fibromyalgia) that, in the
opinion of the Investigator, would interfere with assessments for this trial.
2. 12-lead ECG demonstrating QTc >460 msec for males and >480 msec for females at Screening;
3. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception from at least 14 days prior to the first dose of trial medication until completion of follow-up procedures. Subjects who will remain on MTX after study completion should avoid pregnancy since MTX can
cause birth defects.
4. Subjects who have received the following prior treatments:
• Within prior 4 weeks of Randomization: Herbal supplements*, corticosteroids by
any route with the exception of a stabilized oral dose of =10 mg of prednisone or
equivalent/day [which is allowed], azathioprine, cyclosporine, anakrina
(Kineret®), etanercept (Enbrel®)
• *Herbal supplements should be handled as follows: 1)Fish oil, flaxseed oil,
borage oil, evening primrose oil, and inert substances such as
glucosamine/chondroitin, as well as vitamin supplements may be continued as
long as doses have been stable for one month prior to randomization 2) Known
pharmacologically active herbal supplements such as St. John’s wort, red yeast
rice, etc. or those with unknown/poorly studied activity are excluded ;
• Within prior 8 weeks of Randomization: Infliximab (Remicade®), adalimumab
(Humira®);
• Within prior 8 weeks of Randomization: Any experimental therapy for RA
(within or outside a clinical trial); with the exception of experimental
NSAID/COX-2 inhibitors or opioids for which a washout interval of not less than
5 half-lives shall apply. (Note: This excludes aspirin =325 mg/day for
nonarthritic reasons provided the dose has been continuous and stable for at least
2 weeks prior to the first dose of study medication.);
• Within prior 3 months of Randomization: abatacept (Orencia®);
• Within prior 12 months of Randomization: rituximab (Rituxan®); Such subjects
must also demonstrate normal CD 20+ lymphocyte counts.
5. Subjects who take lithium or warfarin within 1 month of randomization;
6. Subjects who take concomitant medications that are CYP3A4 inhibitors or CYP3A4
inducers (Appendix 1);
7. Subjects who take opioid analgesics at a dose of >30 mg oral morphine or
equivalent/day;
8. Any retinal abnormalities noted during ophthalmoscopic examination at Screening;
9. Subjects with a clinical diagnosis of glaucoma or other diseases affecting the
posterior segment of the eye such as choroiditis, retinitis, chorioretinitis, uveitis,
diabetic proliferative retinopathy, or diabetic macular edema; or any subject with
significant cataracts or other eye pathology which restricts the ability to view the
retina with ophthalmoscopy;
10. Any condition possibly affecting oral drug absorption (eg, gastrectomy or clinically
significant diabetic gastroenteropathy); Bariatric procedures (such as banding) that
effectively divide the stomach but do not affect digestive/absorptive surface area of
the stomach or intestines are NOT exclusionary;
11. Tuberculosis without treatment and/or positive tuberculin reaction by PPD test
without known history of vaccination with the Bacillus Calmette-Guérin (BCG)
vaccine [only in subjects whose last BCG was =50 years prior to screening who do
not have locally-defined risk factors
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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Rheumatoid Arthritis
MedDRA version: 9.1
Level: LLT
Classification code 10039073
Term: Rheumatoid arthritis
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Intervention(s)
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Product Name: CE-224,535
Pharmaceutical Form: Tablet
CAS Number: 724424-43-5
Current Sponsor code: CE-224,535
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125 mg-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
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Primary Outcome(s)
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Secondary Objective: The secondary objectives of this study are:
1. To evaluate the safety and tolerability of CE-224,535 in subjects with active RA on a background of MTX.
2. To evaluate health and functional status.
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Main Objective: The primary objective of this study is to test the efficacy of CE-224,535 vs placebo as
assessed by the American College of Rheumatology 20 (ACR 20) Response Rate at 12 weeks in RA subjects inadequately controlled on methotrexate (MTX).
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Primary end point(s): The primary endpoint is the ACR 20 Responder Rate at Week 12.
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Secondary ID(s)
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2008-000327-25-ES
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A6341009
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date: 15/05/2008
Contact:
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