Rheumatoid arthritis. MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Sponsors
Merck Serono International
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The trial will enrol male and female subjects ³18 years of age at the time of Informed Consent who have rheumatoid arthritis satisfying American College of Rheumatology criteria and a disease history of at least 12 months. Subjects must have active disease; defined by ³8 swollen joints (out of 66), ³8 tender joints (out of 68) and CRP ³6 mg/L or ESR ³28 mm/h. Subjects must have received previous treatment with rituximab and must be candidates for re-treatment with rituximab: i.e. they must have a documented response after an observation period of at least 16 weeks from initiation of treatment to a previous course of rituximab treatment given at least 24 weeks before SD1 and they must have significant residual active disease after previous rituximab treatment or clinical deterioration after initial response (defined by satisfying the above criteria for active disease).Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for four weeks before SD1, during the treatment period and for 12 months after the last dose of rituximab, and must have a negative urine pregnancy test at the screening visit and at SD1. Are the trial subjects under 18? yes 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
Exclusion criteria
Exclusion criteria: Main exclusion criteria are: · Neurological disease. · Inflammatory joint disease other than RA. · Any contraindication to rituximab as per national label. · Known presence of human anti-chimeric antibodies (HACA) to rituximab. · Use of disease-modifying anti-rheumatic drugs (DMARDs; including methotrexate) for less than 3 months or change in dosing regimen within 28 days before SD1, or methotrexate dose regimen >25 mg/week. · Participation in any interventional clinical trial within 1 month before SD1 (or within 5 half-lives of the investigated compound before SD1, whichever is longer). · Prednisone dose regimen >10 mg/day (or equivalent), or change in steroid dosing regimen within 28 days before SD1. · Active or latent tuberculosis within the year before screening or major infection requiring hospitalisation or intravenous anti-infectives within 28 days before SD1. · Serum IgG below 6 g/L. · Known hypersensitivity to atacicept or to any of the components of the formulated atacicept. · Known hypersensitivity to rituximab, to any of the components of the formulated rituximab or to murine proteins. · Breastfeeding or pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the safety and tolerability of combined treatment with atacicept and rituximab in subjects with active rheumatoid arthritis receiving re-treatment with rituximab.;Secondary Objective: The secondary objective of this study are: - to evaluate the effect of combined treatment with atacicept and rituximab on levels of peripheral blood B cell populations over time - to gain further information on the effect of combined treatment with atacicept and rituximab on biomarkers reflecting their mechanism of action (MoA) and disease activity - to characterise the pharmacokinetic (PK) profiles of atacicept and rituximab when given in combination - to identify potential associations between gene polymorphisms and drug response, at a genome scale and with a focus on BLyS, APRIL, BAFF-R, TACI, BCMA and HLA-DRB1 - to investigate the preliminary efficacy of combined treatment with atacicept and rituximab compared to rituximab alone in the treatment of signs and symptoms in a population of subjects with active RA receiving re-treatment with rituximab.;Primary end point(s): . Nature, incidence and severity of adverse events (AEs); in particular, proportion of subjects with treatment-emergent infection-related AEs and proportion of subjects with serious infections. · Proportion of subjects who develop IgG <3 g/L. · Changes and abnormalities in vital signs and routine safety laboratory parameters. · Changes over time in vaccine immunisation status, assessed through anti-tetanus toxoid, anti-pneumococcus and anti-diphtheria toxoid antibody titres. | — |
Countries
Finland, France, Netherlands, Sweden, United Kingdom
Outcome results
None listed