Atacicept Demonstrating Dose RESponSe

NCT01440231 | Withdrawn Phase 2 DMC

• 2 other identifiers: EMR 700461-018BB-IND 11,584
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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 \[SF-36\].

Conditions

Systemic Lupus Erythematosus

Keywords

Rheumatology; Double-Blind; Placebo-Controlled; Multidose; Dose-Response; Phase II; Systemic Lupus Erythematosus; SLE; Atacicept

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

Study Arms (5)

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

Interventions

Placebo DRUG

Matching placebo administered by subcutaneous injection, once weekly

Arm 1

Atacicept DRUG

Atacicept 5 mg administered by subcutaneous injection, once weekly

Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono: lead

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

TACI receptor-IgG Fc fragment fusion protein

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Stephen Wax, MD, PhD

  EMD Serono, Senior Medical Director, Rheumatology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2011
• First Posted: September 26, 2011
• Study Start: February 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: February 1, 2014
• Last Updated: August 21, 2013

Record last verified: 2013-08