Active Rheumatoid Arthritis incompletely responsive to methotrexate MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: ARRY-438162
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: ARRY-438162
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutic
Sponsors
Array BioPharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial: 1. Has provided written informed consent and is willing to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures; 2. Male or female =18 years of age; 3. Has received a stable dose of methotrexate (=10 mg = 25 mg weekly) for = 6 weeks prior to screening and is willing to continue on this regimen for duration of study; 4. Has never received biological agents including but not limited to [Enbrel® (etanercept), Remicade® (infliximab), Humira® (adalimumab), Kineret® (anakinra), Orencia® (abatacept), Rituxan (rituximab) and others listed in Appendix 5] for the treatment of RA and agree not to do so for duration of study; 5. Has been diagnosed with RA prior to the Screening visit based upon the American College of Rheumatology (ACR) 1987 Revised Criteria, fulfilling at least 4 of the following 7 criteria. The first 4 criteria must have been present for at least 6 weeks: a. Morning stiffness in and around any joint for more than 1 hour; b. Soft tissue swelling of 3 or more joint areas; c. Swelling of the proximal interphalangeal (PIP), metacarpophalangeal (MCP), or wrist joints; d. Symmetrical joint swelling; e. Rheumatoid nodules; f. Serum rheumatoid factor positive; g. Radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. 6. The diagnosis of RA must have been present for at least 3 months. 7. Has a minimum current level of disease activity characterized by: a. = 6 tender joints: Tender Joint Count (TJC) (28-joint count), AND b. = 6 swollen joints: Swollen Joint Count (SJC) (28-joint count), AND c. C-reactive protein (CRP) =1.0 mg/dL (10 mg/L) 8. Meets the ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II, or III (Appendix 2); 9. Has completed a 4-week washout period, unless otherwise indicated (calculated from first dose of study drug) if treated with any of the following therapies: a. DMARDs—leflunomide (Arava) (See additional washout information for leflunomide in Section 6.7), auranofin (oral gold), injectable gold (aurothioglucose or aurothiomalate), sulfasalazine, or d-penicillamine; b. Immunosuppressive/Immunomodulatory therapies—azathioprine, cyclosporine, minocycline, and PROSORBA® device/column; c. Any experimental therapy for RA (within or outside a clinical trial setting) within 8 weeks of screening; Prior treatment with any Biologic Response Modifier (BRM) is excluded. d. Participation in another clinical trial within 30 days of screening; e. Other—herbal medications, immunization with any live virus vaccination (e.g., FluMist.), intra-articular, intramuscular, or intravenous corticosteroids; f. Vitamin D supplements > 800 IU per day. 10. Patients may continue on stable background therapy for RA (Doses should be stable for at least 6 weeks prior to first dose of study drug and remain unchanged during the 12-week Treatment Period, unless patient stops due to documented disease improvement, with Sponsor approval), if it includes: a. Non-investigational NSAIDs or COX-2 inhibitors; b. Low-dose oral corticosteroids (=10 mg prednisone or equivalent per day); c. Opioid analgesics (= 30 mg oral morphine or equivalent per day – Appendix 6); d. Acetaminophen (paracetamol) = 2600 mg/day (2.6 g/day) e. Aspirin if taken for nonarthritic reasons, = 325 mg/day; f. Antimalaria
Exclusion criteria
Exclusion criteria: Patients presenting with any of the following will not be included in the trial: 1. Patients with a diagnosis of any other inflammatory or non-inflammatory arthritis (e.g. spondyloarthropathies; fibromyalgia, psoriatic arthritis, crystal proven gout) that may interfere with disease activity assessments or clinically apparent osteoarthritis which would affect subsequent efficacy measures; 2. Patients with a history of: a. Severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological disease or severe systemic involvement with rheumatoid arthritis including rheumatoid vasculitis, Felty’s syndrome or pulmonary fibrosis within 6 months of first dose of study drug; b. Significant associated cardiac disease:, myocardial infarction within 6 months of screening, unstable angina, congestive heart failure (New York Heart Association (NYHA) Class III-IV), known arrhythmias of ventricular etiology, unexplained syncope or syncope/seizures related to arrhythmia (Appendix 4); c. Chronic or recent serious or life-threatening infection within 6 months of first dose (defined as requiring parenteral antibiotics or hospitalization); d. Active tuberculosis or history of tuberculosis without documented curative treatment and/or positive tuberculin reaction to PPD (Purified Protein Derivative) without known vaccination with the bacillus Calmette-Guerin vaccine (BCG). Prior history of BCG with clearly defined scar, are exempt from PPD test and chest X-ray. Refer to Section 9.2.5. for further clarification; e. A positive T-SPOT™TB, where used or comparable diagnostic test; f. Significant trauma or major surgery within 8 weeks of first dose of study medication; g. History of alcohol abuse with less than 12 months of sobriety; or any drug abuse within 3 years of screening visit; h. Cancer, which has been in remission for = 5 years excluding patients with adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. 3. Patients presenting with: a. Any condition possibly affecting oral drug absorption (e.g. gastrectomy, any malabsorption syndrome or clinically significant diabetic gastroenteropathy); b. Any clinically significant skin lesions as described in CTCAE Version 3.0 (Appendix 3); c. A documented body temperature >37.5°C (99.5°F) at Baseline; d. An infection with human immunodeficiency virus (HIV) or hepatitis B or C; e. Any clinically significant active infection including herpes lesions; f. A confirmed mean of the Screening triplicate QTc interval >450 ms; 4. Evidence of organ dysfunction or hematopoietic disorder based on any of the following assessments: a. Hgb =10 g/dL, Hct = 32%; b. Absolute WBC count = 3.0 × 109/L (1x the upper limit of normal (ULN)]; k. TSH = 1.2 ULN unless clinically euthyroid and receiving a stable dose of thryroxine 5. Patients requiring prohibited concomitant medications including CYP3A inhibitors, CYP3A inducers
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To evaluate the pharmacokinetic profiles of multiple doses of ARRY-438162 administered for 12 weeks to patients with active RA; • To evaluate the dose- and concentration-response of ARRY-438162 against measures of disease activity through 12 weeks of treatment. ;Primary end point(s): • American College of Rheumatology 20% (ACR20) response rate at Week 12 ;Main Objective: • To compare the efficacy of 3 dose levels of ARRY-438162 (10 mg BID, 40 mg QD, and 20 mg BID) versus placebo, administered over 12 weeks for the treatment of the signs and symptoms of patients with RA. • To determine the American College of Rheumatology 20% (ACR20) best response rate at Week 12 of patients treated with any well-tolerated dose. • To evaluate the safety of ARRY-438162 in patients with active RA on stable doses of methotrexate (=10 mg = 25 mg) for = 6 weeks. | — |
Countries
Hungary, Poland
Outcome results
None listed