Atacicept Demonstrating Dose RESponSe

NCT01440231 — Phase 2, Withdrawn, EMD Serono

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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)

Registry	NCT01440231, acronym ADDRESS
Status	Withdrawn
Phase	Phase 2
Study type	Interventional; randomized, parallel, masking: quadruple, treatment
Sponsor	EMD Serono (Industry)
Conditions	Systemic Lupus Erythematosus
Interventions	Placebo, Atacicept (Drug)
Dates	start 2012-02-01, primary completion 2013-08-01 (estimated), completion 2014-02-01 (estimated), first posted 2011-09-26, last updated 2013-08-21

-Summary

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 \[SF-36\].

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+Arms and interventions

Arm	Type	Interventions
Arm 1	Placebo comparator	Drug: Placebo
Arm 2	Experimental	Drug: Atacicept
Arm 3	Experimental	Drug: Atacicept
Arm 4	Experimental	Drug: Atacicept
Arm 5	Experimental	Drug: Atacicept

Placebo (Drug): Matching placebo administered by subcutaneous injection, once weekly
Atacicept (Drug): Atacicept 5 mg administered by subcutaneous injection, once weekly
Atacicept (Drug): Atacicept 25 mg administered by subcutaneous injection, once weekly
Atacicept (Drug): Atacicept 75 mg administered by subcutaneous injection, once weekly
Atacicept (Drug): Atacicept 115 mg administered by subcutaneous injection, once weekly

+Outcome measures

Primary outcomes

Change from baseline (trial day 1) in SLEDAI-2K Responder Index-50 (SRI-50) at week 24 of therapy [24 weeks]: 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).

Secondary outcomes

Change from baseline to Week 24 in corticosteroid dose [24 weeks]
Change from baseline in serum Complement C3 levels at week 24 in subjects with low C3 at baseline [24 weeks]
Change from baseline in serum Complement C4 levels at week 24 in subjects with low C4 at baseline [24 weeks]
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 [24 weeks]
Change from baseline in levels of total Ig and Ig classes (IgG, IgA, and IgM) at week 24 [24 weekls]
The nature (preferred terms) and incidence of AEs [24 weeks]: Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Male or female of ≥18 years of age
* Written informed consent
* Diagnosis of SLE satisfying at least 4 out of the 11 ACR criteria during the course of their illness
* Disease duration of at least 6 months
* SLEDAI-2K score ≥ 6 at screening
* Positive test results for antinuclear antibody (ANA) (HEp-2 ANA ≥1:80) and/or anti-double-stranded deoxyribonucleic acid (dsDNA) (≥30 IU/mL) at screening
* Negative serum pregnancy test and highly effective method of contraception for woman of childbearing potential.

Exclusion Criteria:

* Increase in dosing of corticosteroids within 2 weeks prior to screening
* Introduction of MMF within 3 months prior to TD1 or increase in dosing within 1 month before screening
* Change in dosing of immunosuppressants or corticosteroids during the screening period
* Serum IgG < 6g/L
* Estimated Glomerular Filtration Rate (GFR) <50 mL/min/1.73m²
* Urinary protein:creatinine ratio >2 mg/mg
* History of demyelinating disease
* Breastfeeding or pregnancy
* Legal or limited legal capacity

Additional exclusion criteria also apply

+Investigators

Stephen Wax, MD, PhD, Study director, EMD Serono, Senior Medical Director, Rheumatology