Atacicept Demonstrating Dose RESponSe (ADDRESS)

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)

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 Overview

• Status: Withdrawn
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Placebo; Drug: Atacicept; Drug: Atacicept; Drug: Atacicept; Drug: Atacicept

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 2	Drug: Atacicept; Atacicept 5 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 25 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 75 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 115 mg administered by subcutaneous injection, once weekly
Experimental: Arm 3	Drug: Atacicept; Atacicept 5 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 25 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 75 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 115 mg administered by subcutaneous injection, once weekly
Experimental: Arm 4	Drug: Atacicept; Atacicept 5 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 25 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 75 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 115 mg administered by subcutaneous injection, once weekly
Experimental: Arm 5	Drug: Atacicept; Atacicept 5 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 25 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 75 mg administered by subcutaneous injection, once weekly; Drug: Atacicept; Atacicept 115 mg administered by subcutaneous injection, once weekly
Placebo Comparator: Arm 1	Drug: Placebo; Matching placebo administered by subcutaneous injection, once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline (trial day 1) in SLEDAI-2K Responder Index-50 (SRI-50) at week 24 of therapy	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).	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen	24 weeks

Collaborators and Investigators

• Sponsor: EMD Serono
• Investigators: Study Director: Stephen Wax, MD, PhD, EMD Serono, Senior Medical Director, Rheumatology

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Anticipated): August 1, 2013
• Study Completion (Anticipated): February 1, 2014

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: September 23, 2011
• First Posted (Estimate): September 26, 2011

Study Record Updates

• Last Update Posted (Estimate): August 21, 2013
• Last Update Submitted That Met QC Criteria: August 20, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Double-Blind; SLE; Systemic Lupus Erythematosus; Phase II; Placebo-Controlled; Rheumatology; Dose-Response; Multidose; Atacicept
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: EMR 700461-018; BB-IND 11,584 (Other Identifier: CDER)