Atacicept Demonstrating Dose RESponSe

Systemic Lupus Erythematosus Clinical Trial

— ADDRESS  

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01440231
• Other study ID #: EMR 700461-018
• Secondary ID: BB-IND 11,584
• Status: Withdrawn
• Phase: Phase 2
• First received: September 22, 2011
• Last updated: August 20, 2013
• Start date: February 2012
• Est. completion date: February 2014

Study information

• Verified date: August 2013
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSouth Africa: National Health Research Ethics Council
• Study type: Interventional

Clinical Trial 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].

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change from baseline to Week 24 in corticosteroid dose		24 weeks	No
Secondary	Change from baseline in serum Complement C3 levels at week 24 in subjects with low C3 at baseline		24 weeks	No
Secondary	Change from baseline in serum Complement C4 levels at week 24 in subjects with low C4 at baseline		24 weeks	No
Secondary	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	No
Secondary	Change from baseline in levels of total Ig and Ig classes (IgG, IgA, and IgM) at week 24		24 weekls	No
Secondary	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	Yes