Atacicept Demonstrating Dose RESponSe (ADDRESS)
Systemic lupus erythematosis (SLE) is an autoimmune disease, meaning that the body's immune system attacks its own organs and tissues. Within the immune system, B-cells and plasma cells make proteins called antibodies, which in autoimmune disease can bind to one's own tissues and are thus referred to as autoantibodies. Atacicept blocks 2 factors in the body, called BLyS and APRIL, which are important for the maintenance of B-cells and plasma cells, and thus the production of antibodies. This study will assess whether treatment with atacicept can reduce SLE disease activity. Atacicept is still an experimental drug, meaning that it is not available outside of a clinical trial, and that its potential benefits and risks have not been fully determined.
A total of 175 subjects are planned to be randomized (35 subjects per treatment arm) in a 1:1:1:1:1 ratio to receive either atacicept 5 mg, atacicept 25 mg, atacicept 75 mg, atacicept 115 mg or matching placebo, given subcutaneously once weekly for 24 weeks.
The primary objective of the trial is to evaluate the efficacy of atacicept compared to placebo in reducing SLE disease activity in subjects treated with standard of care (SoC) therapy and to investigate the dose-response relationship.
The secondary objectives of the trial are:
- To evaluate the effect of atacicept in reducing corticosteroid usage
- To evaluate the safety and tolerability profile of atacicept in subjects with SLE
- To confirm the PK and PD profiles of atacicept in SLE subjects
- To evaluate the changes in the Medical Outcomes Study Short Form General Health Survey [SF-36].
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase II, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multidose, 24-Week Dose-Response Study to Evaluate the Efficacy and Safety of Atacicept in Subjects With Systemic Lupus Erythematosus (SLE)|
- Change from baseline (trial day 1) in SLEDAI-2K Responder Index-50 (SRI-50) at week 24 of therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]The SRI-50 is a modification of the SLEDAI-2K, and allows detection of partial improvements (at least 50%) in SLE signs and symptoms assessed by SLEDAI-2K (Systemic Lupus Erythamtosus Disease Activity Index- 2000).
- Change from baseline to Week 24 in corticosteroid dose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Change from baseline in serum Complement C3 levels at week 24 in subjects with low C3 at baseline [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Change from baseline in serum Complement C4 levels at week 24 in subjects with low C4 at baseline [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Change from baseline in anti-dsDNA antibodies (in subjects with anti dsDNA ≥30 IU/mL at baseline) and in ANA levels (in subjects with HEp-2 ANA ≥1:80 at baseline) at week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Change from baseline in levels of total Ig and Ig classes (IgG, IgA, and IgM) at week 24 [ Time Frame: 24 weekls ] [ Designated as safety issue: No ]
- The nature (preferred terms) and incidence of AEs [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||February 2014|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Arm 1||
Matching placebo administered by subcutaneous injection, once weekly
|Experimental: Arm 2||
Atacicept 5 mg administered by subcutaneous injection, once weekly
|Experimental: Arm 3||
Atacicept 25 mg administered by subcutaneous injection, once weekly
|Experimental: Arm 4||
Atacicept 75 mg administered by subcutaneous injection, once weekly
|Experimental: Arm 5||
Atacicept 115 mg administered by subcutaneous injection, once weekly
Please refer to this study by its ClinicalTrials.gov identifier: NCT01440231
|Study Director:||Stephen Wax, MD, PhD||EMD Serono, Senior Medical Director, Rheumatology|