Atacicept Demonstrating Dose RESponSe (ADDRESS)

Merck KGaA (EMD Serono)

Status and phase: Withdrawn; Phase 2

Conditions: Systemic Lupus Erythematosus

Treatments: Drug: Atacicept; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01440231

EMR 700461-018

BB-IND 11,584 (Other Identifier)

Details and patient eligibility

About

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].

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 5 patient groups, including a placebo group

Arm 1

Placebo Comparator group

Treatment:

Drug: Placebo

Arm 2

Experimental group

Treatment:

Drug: Atacicept

Drug: Atacicept

Drug: Atacicept

Drug: Atacicept

Arm 3

Experimental group

Treatment:

Drug: Atacicept

Drug: Atacicept

Drug: Atacicept

Drug: Atacicept

Arm 4

Experimental group

Treatment:

Drug: Atacicept

Drug: Atacicept

Drug: Atacicept

Drug: Atacicept

Arm 5

Experimental group

Treatment:

Drug: Atacicept

Drug: Atacicept

Drug: Atacicept

Drug: Atacicept