A Phase IIa, Multi-Centre, Randomized, Double-Blind, Two-Part, Controlled, Repeated-Dose Study of AK106-001616 in Patients with Rheumatoid Arthritis

• Conditions: Rheumatoid arthritis; MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

• Registration Number: EUCTR2008-006075-75-CZ
• Lead Sponsor: Asahi Kasei Pharma Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-28
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

1. Diagnosed as having adult-onset RA (defined by the 1987 American College of Rheumatology [ACR] classification criteria) for duration of at least 3 months.
2. Functional Capacity Classification of I-III (detailed in Appendix F).
3. Aged between 18 and 65 years inclusive.
4. Has been stable on MTX therapy (5 to 25 mg administered as a single weekly dose) for at least 12 weeks.
5. Women of childbearing potential must confirm use of adequate contraception since last menses, must confirm continued use of adequate contraception during the study, must have a negative urine pregnancy test before administration of study drug and must be willing to use adequate contraception for 3 months from the end of the study. Adequate contraception is defined as the use of two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide). A condom alone is not considered an acceptable method of birth control.
6. Male patients with a female partner of childbearing potential must be willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide) during the study and for 3 months following administration of the study drug.
7. Patients must have a negative urine screen for drugs of abuse.
8. Patients must have negative screening for hepatitis B (hepatitis B surface antigen [HBsAg] negative) and hepatitis C (negative anti-hepatitis c virus [HCV]).
9. Must be able to communicate well with the investigator, to understand and comply with the requirements of the study, and be judged suitable for the study in the opinion of the investigator.
10. Able to give voluntary written informed consent to participate in this trial.

Part 1 only:
If the subject has been using non-steroidal anti-inflammatory drugs (NSAIDs) prior to this study they must be on a stable NSAID therapy and have a Functional Capacity Classification (detailed in Appendix F) that has not changed for at least 4 weeks.

Part 2 only:
Patient has RA activity at screening and baseline (Day 1, pre-morning dose), defined as a disease activity score (DAS28) score of = 3.2, and a change in DAS28 score from screening to baseline that is > 0 and = 1.2 (baseline – screening).

Additional criterion for inclusion in the sub-group of patients who have their synovial fluid sampled:
Aspiration of synovial fluid from the knee joint is clinically indicated in the opinion of the investigator.

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) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects will be excluded from participation in the study if any of the following criteria are met at screening and at baseline:

1. Has been diagnosed with a secondary, non-inflammatory type of arthritis (e.g., osteoarthritis or fibromyalgia) that might interfere with the evaluation of the effect of study medication on RA symptoms.
2. Pregnant or breastfeeding.
3. Taken any NSAID (including aspirin) within at least 5 times the half-life of the NSAID (at least 2 days) before the baseline visit or any analgesic within 24 hours before the baseline visit. In Part 2 only, patients taking = 150 mg aspirin per day for non-arthritis reasons for at least 30 days before the first dose of study medication will be permitted to enter the study and will be allowed to continue their aspirin regimen for the duration of the study.
4. Taken any anti-ulcer drugs (i.e., H2 blockers, proton pump inhibitors, etc) during the time of NSAID washout.
5. Treated with:
- Anti-tumour necrosis factor (TNF) drugs or other biologicals (except rituximab) e.g. anakinra, abatacept, in the past 3 months.
- Rituximab in the past 6 months.
6. Has begun taking any of the following medications or has changed the dosing regimen of any of these medications within 12 weeks before receiving the first dose of study medication:
- Gold salts (including oral gold);
- Sulfasalazine;
- MTX;
- Azathioprine;
- Antimalarials;
- Penicillamine;
- Combination therapies used in RA treatment;
- Leflunomide.
7. Has begun taking oral corticosteroids or changed the dose regimen of oral corticosteroids within 4 weeks before receiving the first dose of study medication (doses of up to 10 mg prednisone or equivalent per day are allowed), or the patient has received intramuscular, intra articular or soft-tissue injections of corticosteroids within 8 weeks before receiving the first dose of study medication.
8. Received any antineoplastic (other than MTX = 25 mg/week or azathioprine as therapy for RA) during the 8 weeks preceding the first dose of study medication.
9. Has an active malignancy of any type or a history of malignancy (with the exception of patients who have been in remission for at least 5 years and patients who have a history of treated basal cell carcinoma and carcinoma in situ of the cervix).
10. (a) Has a history of 2 or more types of active peptic ulceration as below:
- GI bleeding;
- Recurrent gastric ulcers;
- Duodenal ulcers.
(b) Has an oesophageal, gastric or duodenal ulcer within 30 days before the first dose of study medication;
(c) Has active GI disease or any condition precluding NSAID therapy.
11. Has clinically significant chronic/acute hepatic or renal disorder or a significant coagulation defect.
12. Has:
- An abnormal screening laboratory test value that is considered by the investigator to be clinically significant, or;
- A value that is > 2 times the upper limit of normal (ULN) for aspartate aminotransferase (AST) or alanine aminotransferase (ALT), or;
- A value for serum creatinine > 1.5 times the ULN at screening, or;
- An absolute neutrophil count (ANC) < 1500/mm3 (or white blood cell count [WBC] < 3 x 109/L), haemoglobin < 8 g/dL or platelets < 100 x 109/L.
13. Has a known hypersensitivity to paracetamol and/or NSAIDs.
14. Has received any investigational medication within 90 days before the first dose of study medication.
15. Has previously been admitted to this study.
16. Has a current uncontrolled medical disorder (myocardial infarction, unstable angina, u

Study & Design

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