Atacicept Demonstrating Dose RESponSe (ADDRESS)

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01440231
First received: September 22, 2011
Last updated: August 20, 2013
Last verified: August 2013
  Purpose

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].

Condition Intervention Phase
Systemic Lupus Erythematosus
Drug: Placebo
Drug: Atacicept
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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


Enrollment: 0
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)
Arms Assigned Interventions
Placebo Comparator: Arm 1 Drug: Placebo
Matching placebo administered by subcutaneous injection, once weekly
Experimental: Arm 2 Drug: Atacicept
Atacicept 5 mg administered by subcutaneous injection, once weekly
Experimental: Arm 3 Drug: Atacicept
Atacicept 25 mg administered by subcutaneous injection, once weekly
Experimental: Arm 4 Drug: Atacicept
Atacicept 75 mg administered by subcutaneous injection, once weekly
Experimental: Arm 5 Drug: Atacicept
Atacicept 115 mg administered by subcutaneous injection, once weekly

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01440231

Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Stephen Wax, MD, PhD EMD Serono, Senior Medical Director, Rheumatology
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01440231     History of Changes
Other Study ID Numbers: EMR 700461-018, BB-IND 11,584
Study First Received: September 22, 2011
Last Updated: August 20, 2013
Health Authority: United States: Food and Drug Administration
South Africa: National Health Research Ethics Council

Keywords provided by EMD Serono:
Rheumatology
Double-Blind
Placebo-Controlled
Multidose
Dose-Response
Phase II
Systemic Lupus Erythematosus
SLE
Atacicept

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 25, 2014