Rheumatoid Arthritis
Conditions
Keywords
TNF inhibitor, Multiple ascending dose study
Brief summary
This primary purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic properties of multiple ascending doses of ATN-103 administered subcutaneously (below the skin) to Japanese subjects with active rheumatoid arthritis and on a stable background of methotrexate. Some subjects will receive ATN-103 while other subjects will receive a placebo.
Interventions
BIOLOGICALATN-103 10 mg q4wks
ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.1 mL) of either ATN-103 or placebo at 4-week intervals for a total of 4 SC injections.
BIOLOGICALATN-103 30 mg q4wks
ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.3 mL) of either ATN-103 or placebo at 4-week intervals for a total of 4 SC injections.
BIOLOGICALATN-103 80 mg q4wks
ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.8 mL) of either ATN-103 or placebo at 4-week intervals for a total of 4 SC injections.
BIOLOGICALATN-103 10 mg q8wks
ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.1 mL) of either ATN-103 or placebo at 8-week intervals for a total of 2 SC injections.
BIOLOGICALATN-103 80 mg q8wks
ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.8 mL) of either ATN-103 or placebo at 8-week intervals for a total of 2 SC injections.
Sponsors
Ablynx, a Sanofi company
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Meets the ACR 1987 revised criteria for classification of Rheumatoid Arthritis (RA). * ACR functional class I through III. * Active RA at the time of screening and at baseline consisting of = 6 swollen and = 6 tender joints at least. * hs-CRP level = 8 mg/L. * Must be receiving MTX for at least 12 wks, with a stable dose and route of MTX for at least 6 wks prior to the baseline and continuing on that dose for the duration of the study. * The report of a chest x-ray performed within 12 wks before the screening documenting the absence of any evidence of malignancy, infection, or abnormalities suggestive of TB must be obtained and available in the subject's study file prior to baseline. * All WOCBP must have a negative pregnancy test result at screening and baseline. * All WOCBP who have sexual intercourse with a nonsurgically sterilized male partner must agree and commit to the use of the following highly effective forms of contraception for the duration of the study and for 8 wks after the last dose of investigational product. * All male subjects who are biologically capable of fathering children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 wks after the last dose of investigational product.
Exclusion criteria
* Pregnant or breastfeeding women. * Presence of active infections or open cutaneous ulcers or any underlying disease that could predispose subjects to infections or history of serious infection within 4 wks before the baseline. * A history or current evidence of latent or active TB, evidence of prior or currently active TB by chest X-ray, recent close contact with an individual with active TB, or a positive Mantoux tuberculin skin test. * Other significant concurrent medical conditions at the time of the screening or baseline. * Laboratory abnormalities at screening. Positive for HBsAg, HBcAb, and/or HepCAb. ALTand/or AST= 2 times the ULN or higher. Hemoglobin = 8.5 g/dL or lower. Platelet = 125,000 /mm³ or lower, or = 1,000,000 /mm³ or higher. WBC = 3500 /mm³ or lower. Serum creatinine= 2 mg/dL or higher. * Any prior use of B cell-depleting therapy. * Receipt within 24 wks before the baseline visit: Any cytotoxic drugs. Leflunomide. Any investigational biological drug(s). * Receipt within 12 wks before the baseline visit: Any biological drugs not listed under the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability will be evaluated on the basis of AEs, SAEs,(including injection site reactions and infections), physical examination findings, vital sign, measurements, immunogenicity assessments, early termination, and clinical laboratory test. | 20 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Clinical efficacy for Rheumatoid Arthritis (RA) based on ACR responses, ACR-N, DAS 28 and EULAR response. | 16 weeks |
Countries
Japan
Outcome results
None listed