A phase II randomised, double-blind, multicenter, placebo-controlled, dose-ranging, parallel group study to compare the efficacy, safety and tolerability of 3 strengths of AD 452 in adult subjects with active rheumatoid arthritis who are currently taking methotrexate. - Efficacy, safety and tolerability of AD 452 in patients wih RA
- Conditions
- MedDRA version: 7.0Level: PTClassification code 10039073The purpose of this clinical trial is to evaluate the clinical efficacy, safety and tolerability of three doses of AD 452 in comparison with placebo in the treatment of subjects with active rheumatoid arthritis.
- Registration Number
- EUCTR2005-002421-31-DE
- Lead Sponsor
- Arakis Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 292
Subjects will be considered eligible if they meet all of the following criteria at the Screening Visit:
- Male or female subjects aged =18 years to =75 years.
- Subjects with a documented diagnosis of adult rheumatoid arthritis according to the revised criteria of the American College of Rheumatology (ACR) – ACR functional classes I-III. Onset must be after age 16 years and duration must have been at least 6 months.
- Subjects must have 4 or more tender or painful joints and 4 or more swollen joints (28 joint count) and CRP greater than or equal to 4mg/L.
- Subjects must be taking MTX (po, sc, im) with a weekly dose in the range of 10-25 mg/week or 7.5 mg if a higher dose was not tolerated. MTX therapy must have been present for 6 months and the dose must have been stable for the last 8 weeks.
- The dose of any other medical therapy for RA (NSAID, COX2, codeine, low dose glucocorticoid (=10mg prednisolone equivalent)) must have been stable for at least 4 weeks.
- Subjects who are able to understand the nature of the study, comply with the protocol for the duration of the study and give 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
Subjects will be ineligible if they meet any of the following criteria:
- Subjects with a history of other inflammatory joint disease, e.g., mixed connective tissue disorder, seronegative spondylarthropathy, psoriatic arthritis, Reiter’s syndrome, systemic lupus erythematosus (SLE), sarcoidosis, synoviorthesis or any arthritis with onset prior to 16 years of age.
- Subjects who are pregnant or breast-feeding. Women of child-bearing potential (including, for example, women who are less than 24 months postmenopausal who have not had hysterectomy or tubal ligation) must be willing and able to use an adequate method of contraception during the course of the study or to practice sexual abstinence and must have a negative pregnancy test prior to receiving study drug.
- Subjects with a change in anti-rheumatic medication (NSAID, COX2, codeine, low dose glucocorticoid) within 4 weeks of the Screening Visit
- Subjects who are on glucocorticoid >10mg prednisolone equivalent or who have been treated with or have planned treatment with depot corticosteroids (including intraarticular or intrasynovial) within 4 weeks of the Screening Visit.
- Subjects who are currently taking or who have taken any investigational drug within 3 months prior to the screening visit (previous participation in protocol P-AD452-019 is acceptable).
- Subjects who require treatment with any other known disease modifying therapy; or halofantrine or mefloquine.
- Subjects with QTc >470ms at baseline.
- Subjects with a known allergy to the study drugs or any of their components.
- Subjects with a presence of any of the following concurrent conditions:
- Diabetes mellitus (insulin dependent or difficult to control)
- History of / or current therapy for lymphoma, leukemia or malignant melanoma
- Active infection
- Known HIV, hepatitis B or hepatitis C positive serology
- History of cardiac conduction disorders (not including grade 1 AV block or incomplete right or left bundle branch block) or uncontrolled hypertension
- Significant hepatic or renal insufficiency (any of the transaminases >2 x upper limit of normal, creatinine > 1.5 x upper limit of normal)
- Evidence or history of alcohol or drug abuse
- Clinically significant abnormal screening laboratory values (not including CRP)
- Hemoglobin <8 g/dcl
- A history of sensitivity to antimalarial or related compounds
- Active depression or a recent history of depression, generalised anxiety disorder, psychosis or schizophrenia or other major psychiatric disorders or convulsions
- Subjects who are unable or unwilling to comply fully with the protocol.
- Subjects who have previously entered this study.
- Subjects whom the investigator believes to be medically unfit to receive the study treatment, or unsuitable for any other reason.
- Subjects who have taken drugs on the following table for which the minimum washout period has not elapsed.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to investigate the clinical efficacy of three doses of AD 452 in the treatment of subjects with active rheumatoid arthritis. ;Secondary Objective: The secondary objective is to assess the safety and tolerability of three doses of AD 452 in subjects with active rheumatoid arthritis.<br><br>In addition, an assessment of the impact of steady state plasma exposure on efficacy and safety will be explored.<br><br><br><br><br>;Primary end point(s): The primary endpoint is the ACR20 response at week 12. <br><br>This is defined as a =20% improvement between visit 2 and visit 6 in tender and swollen joints count and =20% improvement between visit 2 and visit 6 in at least 3 of the following 5 ACR core set measures: pain, physician global assessment, subject global assessment, HAQ and CRP.<br>
- Secondary Outcome Measures
Name Time Method