A Phase 2 placebo-controlled study to compare the effectiveness and safety of two doses of apremilast (CC-10004) in subjects with active rheumatoid arthritis, who have not responded to methotrexate treatment

• Conditions: Rheumatoid arthritis, a chronic systemic autoimmune inflammatory disease characterized by persisten synovial inflammations.; MedDRA version: 14.0Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2010-019926-15-CZ
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-01
• Last Update Posted: 16 September 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 210

Inclusion Criteria

General Subject Population:
1. Male or female, must be age = 18 years at the time of consent.
2. Must understand and voluntarily sign an informed consent form prior to any study related assessments/procedures are conducted.
3. Must be able to adhere to the study visit schedule and other protocol requirements. Disease Specific Parameters:
4. Must have a documented diagnosis of RA (1987 ACR Criteria, Appendix A) with onset of signs/symptoms of disease = 4 months of duration from randomization.
5. Must be receiving treatment on an outpatient basis.
6. Must have active disease despite current methotrexate treatment as defined below:
= 6 swollen joints (66 swollen joint count) at randomization (Visit 2) AND
= 6 tender joints (68 tender joint count) at randomization (Visit 2)
7. Must meet at least one of the four lab requirements below:
- hsCRP = 10 mg/L
- ESR > 28 mm after the first 1 hour
- Positive for RF
- Positive for anti-CCP antibodies
8. For subjects participating in the MRI assessment:
-Must have RA joint involvement, as assessed by swollen joint counts in: 1) at least
two MCP swollen joints on the same hand, or 2) at least one swollen MCP joint and
swollen wrist on the same hand.

Current Treatment:
9. Must have been treated with methotrexate for at least 4 months prior to randomization, and must be on stable dose between 7.5 and 25 mg/week (oral or parenteral) for at least 4 weeks prior to randomization. Subjects will be required to maintain their stable dose through Week 52 of the study. Oral folate (folic acid) supplementation is required with a minimum dose of 5 mg/week, or instead leucovorin may be used up to 10 mg/week orally.
10. NSAIDs and pain medications are allowed, however, must be on stable regimen for at least 7 days prior to randomization and through Week 52 of the study.
11. Oral corticosteroids (if taken) are allowed, however, must be on stable dose of prednisone = 10 mg/day or equivalent for at least 28 days prior to randomization and through Week 52 of the study.

Laboratory Measures:
12. Must meet the following laboratory criteria at screening:
- White blood cell count = 3000/mm3 (= 3.0 x 109/L) and < 14,000/mm3 (< 14 x
10^9/L)
- Platelet count = 100,000/µL (= 100 x 109/L)
- Serum creatinine = 1.5 mg/dL (= 132.6 µmol/L)
- AST (SGOT) and ALT (SGPT) = 2 x upper limit of normal (ULN). If initial test
shows ALT or AST > 2 times the ULN, one repeat test is allowed during the
screening period.
- Total bilirubin = 2 mg/dL (= 34 µmol/L). If initial test result is > 2 mg/dL, one repeat
test is allowed during the screening period.
- Hemoglobin = 9 g/dL (= 5.6 mmol/L)
- Hemoglobin A1c = 9.0%
- Negative for hepatitis B surface antigen
- Negative for hepatitis C antibody

Contraception Requirement:
13. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on IP and for at least 28 days after the last dose of IP.

14. Females of childbearing potential (FCBP)† must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use contraception‡ while on IP and for at least 28 days after taking the last dose of IP with either: 1) one highly effective form (non-oral hormonal, intrauterine device [IUD], tubal ligation, vasectomized partner); or 2) an or

Exclusion Criteria

Disease Specific Requirements:
1. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
2. Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis or significant systemic involvement secondary to RA (eg, vasculitis, pulmonary fibrosis or Felty syndrome). Sjögren syndrome secondary to RA is allowable.
3. Functional Class IV as defined by the ACR Classification of Functional Status in
Rheumatoid Arthritis (Appendix B).
4. Prior history of, or current, inflammatory joint disease other than RA (eg, gout, reactive arthritis, psoriatic arthritis, ankylosing spondylitis, Lyme disease).

Previous and Current Medications/Therapy:
5. Receiving treatment with DMARDs (other than MTX), including biologic DMARDs.
Previous use is only allowed after adequate washout prior to randomization.
6. Inadequate response to treatment with an anti-TNF agent. Patients who terminated previous anti-TNF treatment due to cost or safety reason, such as discomfort with the subcutaneous injections, may participate in this study after adequate washout.
7. Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.
8. Previous treatment with any cell depleting therapies, including investigational agents (eg, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20).
9. Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 6 months of baseline.
10. Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.
11. Any previous treatment with alkylating agents such as cyclophosphamide or
chlorambucil, or with total lymphoid irradiation.

General Health:
12. Pregnant women or nursing (breast feeding) mothers.
13. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including severe or very severe chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus as defined by HbA1c > 9.0%) or gastrointestinal (GI) disease.
14. Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
15. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.
16. History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired
immunodeficiency (eg, Common Variable Immunodeficiency Disease).
17. History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured).
18. History of alcohol, drug or chemical abuse within the 6 months prior to screening.
19. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
20. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
21. Any condition that i

Study & Design

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