A 16-week multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-finding study to evaluate the efficacy, safety and tolerability of subcutaneous AIN457 followed by an extension phase up to a total of 60 weeks in patients with active rheumatoid arthritis despite stable treatment with methotrexate - F2201

• Conditions: Moderate to severe Rheumatoid Arthritis.; MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

• Registration Number: EUCTR2009-011000-34-CZ
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06-15
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

? Male or non-pregnant, non-lactating females at least 18 years of age.

? Presence of RA classified by ACR 1987 revised criteria. Patients with active RA must have been on MTX for at least 3 months and must currently be treated with a stable dose of MTX (=7.5 mg/week - =25 mg/week) for at least 4 weeks.

? At Baseline: Disease activity criteria defined by =6 out of 28 tender joints and =6 out of 28 swollen joints. WITH either a.Screening value of hsCRP = 10 mg/L b.OR ESR =28 mm/1st hr

? Patients who failed any DMARD including biologic DMARDs and any DMARDs used in combination with MTX will be allowed entry into study after appropriate wash-out period (except for MTX) prior to baseline:

28 days for DMARDs , except for leflunomide, which has to be discontinued for 8 weeks prior to baseline unless a cholestyramine washout has been performed.

7 days for Kineret – with a terminal half-life of 4 to 6 hours (s.c. route).

4 weeks for Enbrel – with a terminal half-life of 102 ± 30 hours (s.c. route).

8 weeks or longer for Remicade – with a terminal half-life of 8.0-9.5 days (i.v. infusion).

12 weeks for Humira – with a terminal half-life of 10-20 days (average 2 weeks) (s.c. route).

12 weeks for Orencia – with a terminal half-life of 13.1 (8-25) days (i.v. infusion).

12 weeks for Cimzia® (certolizumab) andn Simponi® (golimumab)
26 weeks for any other biologic – or 10 half-lives, which ever is longer.

? Patients taking systemic corticosteroids have to be on a stable dose of =10 mg/d prednisone or equivalent for at least 4 weeks before randomization.

? Patients who are regularly taking NSAIDs or COX-2 inhibitors or paracetamol/ acetaminophen as part of their RA therapy must be on a stable dose for at least 4 weeks before randomization.

? Patients taking NSAIDs or COX-2 inhibitors or paracetamol/acetaminophen PRN within 2 weeks before randomization have to stop their medication at least 24 hours before an ACR visit

? Patients must taking folic acid supplementation have to be on stable dose for at least 4 weeks before randomization.

? All patients receiving current vaccinations, especially influenza and pneumococcal as clinically indicated can be included.
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

? RA patients functional status class IV classified according to the ACR 1991 revised criteria

? Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, or morphine)

? Any therapy by i.a. (e.g. steroids) required for treatment of acute RA flare within 4 weeks before randomization.

? Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)

? WCBP, defined as all women physiologically capable of becoming pregnant, UNLESS using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some IUDs, Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable

? Males who do not consent to practice contraception during study (for details see protocol).

? Inflammatory diseases other than RA that might confound the evaluation of the benefit of AIN457, thus other rheumatic diseases that could confound the evaluation of efficacy, including but not limited to primary fibromyalgia, ankylosing spondylitis, Lyme disease, adult JRA,SLE, gout and pseudo gout, vasculitis, PsA, reactive arthritis, primary Sjoegren’s, and Behcet’s.

? Underlying metabolic, hematologic, pulmonary, neurologic, encocrine renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in an immunodulatory therapy. In particular, clinical evidence or history of Felty’s syndrome.

? With significant medical problems, including but not limited to the following: uncontrolled hypertension (=160/95 mmHg), congestive heart failure [NYHA III or IV ].

?

? Active systemic infections during the last two weeks (exception: common cold) prior to randomisation.

? History of, or ongoing, chronic or recurrent infectious disease or evidence of previous tuberculosis infection. Patients with evidence of latent tuberculosis may enter the trial after sufficient treatment has been initiated according to local regulations. Prior to study entry all patients will be tested for tuberculosis status according to local guidelines

? Known infection with HIV, HEP B or C at screening or randomisation..

? History of lymphoproliferative disease or any known malignancy or history of malignancy within the past 5 years (except for non-melanoma skin cancer that has been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix, colon polyps with non-invasive malignancy that have been removed).

? Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the patient unsuitable for the trial.

? Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins).

? Any medical or psychiatric condition which, in the Investigator’s opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.

? Donation or loss of 400 mL or more of blood within 8 weeks before dosing.

? History orevidence of ongoing drug/alcohol abuse, or history thereof within the last six months before first study drug administration

? Previous exposure to AIN457

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Efficacy of AIN457 at 16 weeks on ACR20 response.;Secondary Objective: 1. Speed of onset of response based on ACR20 and ACR50 at 2, 4 and 8 weeks.<br><br>2. Response to treatment (ACR 50/70, DAS 28) compared to placebo at week 16.<br><br>3. Effect of AIN457 on ACR components, including hsCRP and ESR to placebo.<br><br>4. Immunogenicity of AIN457.<br><br>5. PK/PD of AIN457 to support the decision making for the posology of Phase III.<br><br>6. Overall safety and tolerability of AIN457.<br><br>7. Efficacy of AIN457 on QoL and fatigue at weeks 0,2,4,8,12,16, (SF 36 & FACIT-Fatigue).;Primary end point(s): ACR20 at 16 weks.