Clinical trial NCT00664521: Atacicept in Combination With Rituximab in Subjects With Rheumatoid Arthritis (August III)
Official title: A Randomized, Double-blind, Placebo Controlled, Multi-centre, Exploratory, Pilot, Phase II Trial of 150mg Atacicept Given Subcutaneously in Combination With Rituximab in Subjects With Rheumatoid Arthritis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2008-04-23
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess the safety and tolerability of combined treatment with atacicept and rituximab in subjects with active rheumatoid arthritis (RA) receiving re-treatment with rituximab.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects
* Greater than and equal to (\>=) 18 years of age at the time of Informed Consent
* Who have rheumatoid arthritis satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 12 months
* Subjects must have active disease defined by DAS28 \>3.2
* Subjects must have received previous treatment with rituximab and must be candidates for re-treatment with rituximab
* Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 4 weeks before study day 1 (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 SD1
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Current neurological disease excluding migraine
* Inflammatory joint disease other than rheumatoid arthritis
* Any contraindication to rituximab as per national label
* 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 hospitalization or intravenous anti-infectives within 28 days before SD1
* Serum Immunoglobulin G (IgG) below 6 gram per liter (g/L)
* Known hypersensitivity to atacicept or to any of the components of the formulated atacicpet
* Known hypersensitivity to rituximab, to any of the components of the formulated rituximab or to murine proteins
* Breastfeeding or pregnancy
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 64
measure: Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L)
timeFrame: Week 64
measure: Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32
timeFrame: Baseline, Week 32
measure: Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32
timeFrame: Baseline, Week 32
measure: Percent Change From Baseline in Anti-pneumococcus Titer at Week 32
timeFrame: Baseline, Week 32
Secondary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32
timeFrame: Week 32
measure: Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32
timeFrame: Baseline, Week 32
measure: Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells
timeFrame: Baseline, Week 3, 7, 12, 16, 26 and 32
Other outcomes:
Locations:
city: Nice
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Malmö
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Newcastle
country: United Kingdom
facility: Research Site
city: Norwich
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: van Vollenhoven RF, Wax S, Li Y, Tak PP. Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial. Arthritis Rheumatol. 2015 Nov;67(11):2828-36. doi: 10.1002/art.39262.