A randomised, double-blind, placebo controlled, multi-centre phase II study of atacicept in anti- TNF alfa-naïve patients with moderate to severely active rheumatoid arthritis and an inadequate response to methotrexate - Atacicept in anti-TNF alfa-naïve subjects with RA
- Conditions
- Rheumatoid arthritisMedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis
- Registration Number
- EUCTR2007-002536-29-SE
- Lead Sponsor
- Merck Serono International
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 264
To be eligible for inclusion in this study, the subjects must fulfil all of the following criteria at the time of screening, unless stated otherwise:
1. Rheumatoid arthritis satisfying American College of Rheumatology (ACR) criteria for RA with a disease history of at least 6 months.
2. Male or female =18 years of age at time of Informed Consent.
3. Active RA as defined by: =8 swollen joints (66 joint count), =8 tender joints (68 joint count), and CRP =10 mg/L and/or ESR =28 mm/hr.
4. Persistent and active RA despite MTX treatment (=15 mg/week) lasting for >3 months.
5. Stable MTX dose (15-25 mg) for at least the last 28 days before SD 1.
6. Written informed consent, obtained before any study-related procedure. Subjects must review and understand the Informed Consent Form, and must fully understand the requirements of the study and be willing to comply with all study visits and assessments.
7. Women of childbearing potential must have a negative urine pregnancy test at the screening visit. For the purposes of this trial, women of childbearing potential are defined as all female subjects after puberty unless they are post-menopausal for at least two years or are surgically sterile.
8. Female patients of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for four weeks prior to, during and three months after the last dose study medication. Women randomized to adalimumab will be required to maintain an adequate method of contraception for at least 5 months after the last dose.For the purposes of this study, women of childbearing potential is defined as: All female patients after puberty unless they are post-menopausal for at least two years, or are surgically sterile. Adequate contraception is defined as two barrier methods, or one barrier method with a spermicide, or an intrauterine device or use of the oral female contraceptive (or other hormonal methods).
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
To be eligible for inclusion in this study the subjects must not meet any of the following criteria at the time of screening:
1. Any condition, including laboratory findings and findings in the medical history or in the pre-study assessments (such as, but not limited to, significant nervous system, renal, hepatic, endocrine or gastrointestinal disorders), which in the Investigator’s opinion constitutes a risk or a contraindication for the subject’s participation in the study or that could interfere with the study objectives, conduct or evaluation.
2. Inflammatory joint disease other than RA.
3. Active alcohol or drug abuse or history of alcohol or drug abuse in the last 6 months.
4. Treatment with DMARDs other than MTX: all DMARDs except MTX should be discontinued >28 days (>60 days for leflunomide) before SD 1.
5. Previous or concurrent treatment with any approved or investigational biological compound for RA, including but not restricted to any anti-TNF alfa agents, rituximab, abatacept, tocilizumab, interleukin-1 receptor antagonist (IL-1Ra) and belimumab.
6. Participation in any interventional clinical trial within 1 month before SD 1 (or within 5 half-lives of the investigated compound before SD 1, whichever is longer).
7. Any contraindication to adalimumab as per national label.
8. Methotrexate dose regimen >25 mg/week.
9. Prednisone dose regimen >10 mg/day (or equivalent) or change in steroid dosing regimen within 28 days before SD 1.
10. Change in NSAID dosing regimen within 28 days before SD 1.
11. More than one intra-articular steroid injection or parenteral glucocorticoid treatment within 28 days before SD 1.
12. Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks of SD1 assessments.
13. Positive HIV, hepatitis C or hepatitis B (HBsAg) serology.
14. Presence of active or latent tuberculosis within the past year before screening. Subjects should be evaluated and screened for active or latent tuberculosis according to national and/or local recommendations.
15. Diagnosis or family history of Creutzfeldt-Jakob disease (CJD).
16. History or presence of uncontrolled or New York Heart Association (NYHA) class 3 or 4 congestive heart failure.
17. History of cancer, except for adequately treated basal cell carcinoma of the skin, cervical dysplasia or carcinoma in situ of the skin or the cervix.
18. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (AP) level >2.5 x ULN or total bilirubin >1.5 x ULN.
19. Inadequate renal function, defined by serum creatinine >1.5 x ULN.
20. Clinically significant abnormality in any haematological test; for example, haemoglobin <5.5 mmol/L (<8.9 g/dL), WBC <2.5 x 109/L, platelets <75 x 109/L.
21. Serum IgG below 6 g/L.
22. Clinically significant abnormality on chest X-ray performed within 3 months before SD 1 or on ECG performed at screening.
23. Known hypersensitivity to atacicept or to any of the components of the formulated atacicept.
24. Known hypersensitivity to adalimumab or to any of the components of the formulated adalimumab.
25. Immunisation with live vaccines or Ig treatment within 28 days before SD 1, or need for such treatment during the study (including follow-up).
26. Any surgical procedure, including bone or joint surgery or synovectomy within 12 weeks before SD 1 or planned major surgery (e.g. joint replacement) duri
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method