Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (APRIL-SLE) (APRIL-SLE)

This study has been completed.
Sponsor:
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00624338
First received: February 15, 2008
Last updated: March 11, 2016
Last verified: March 2016
  Purpose
This study is to evaluate the efficacy and safety of atacicept compared to placebo in preventing new flares in subjects with systemic lupus erythematosus (SLE) and to confirm the optimal dose of atacicept for treatment of subjects with SLE and gain information on the effect of atacicept on markers specific to its mechanism of action (MoA) and their correlation to disease activity/progression. Study medication will be administered through subcutaneous (under the skin) injections, beginning with twice weekly injections for the first 4 weeks, followed by once weekly doses for 48 weeks. Following the last treatment, a safety follow-up period of 24 weeks will be conducted.

Condition Intervention Phase
Lupus Erythematosus, Systemic
Drug: Atacicept 75 mg
Drug: Atacicept 150 mg
Other: Placebo Comparator
Phase 2
Phase 3

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 Randomised, Double-blind, Placebo Controlled, Multicentre Prospective Dose-finding Phase II/III Study With Atacicept Given Subcutaneously to Subjects Having Recently Experienced a Flare of Systemic Lupus Erythematosus (SLE)

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Percentage of Participants Experiencing a New Flare as Defined by British Isles Lupus Assessment Group (BILAG) Score A or B [ Time Frame: From screening up to Week 52 ] [ Designated as safety issue: No ]
    A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment, or imputed for participants who had premature treatment discontinuation. Discontinuations due to sponsor termination of the atacicept 150 mg group were not imputed as flares in this analysis. The BILAG disease activity index evaluates systemic lupus erythematosus (SLE) activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.


Secondary Outcome Measures:
  • Time to First New Flare as Defined by BILAG Score A or B [ Time Frame: From screening up to Week 52 ] [ Designated as safety issue: No ]
    A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment. Analysis was right-censored at Week 52. The hazard ratios and 95% confidence intervals were obtained from the Cox proportional hazards model. The 25th Percentile of time to new flare was reported using Kaplan-Meier estimates (Median was not reached). The BILAG disease activity index evaluates SLE activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, NSAIDs, or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.

  • Percentage of Participants Experiencing a New Flare as Defined by BILAG Score A or B During Initial 24 Weeks [ Time Frame: From screening up to Week 24 ] [ Designated as safety issue: No ]
    A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment, or imputed for participants who had premature treatment discontinuation. The BILAG disease activity index evaluates SLE activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, NSAIDs, or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.

  • Percentage of Participants Within Ordinal Response Categories for British Isles Lupus Assessment Group (BILAG) Flares [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Ordinal response categories have been defined as: 1) No BILAG A, no BILAG B, and completed treatment, 2) No BILAG A, at least 1 BILAG B during treatment period, and 3) At least 1 BILAG A during treatment period. The BILAG disease activity index evaluates SLE activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, NSAIDs, or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.

  • Mean Cumulative Corticosteroid Dose [ Time Frame: Randomization up to Week 52 ] [ Designated as safety issue: No ]

Enrollment: 461
Study Start Date: January 2008
Study Completion Date: October 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atacicept 75 mg Drug: Atacicept 75 mg
75 milligram (mg) atacicept injection will be administered subcutaneously twice weekly during initial loading period for 4 weeks followed by once weekly during maintenance period for subsequent 48 weeks.
Experimental: Atacicept 150 mg Drug: Atacicept 150 mg
150 mg atacicept injection will be administered subcutaneously twice weekly during initial loading period for 4 weeks followed by once weekly during maintenance period for subsequent 48 weeks.
Placebo Comparator: Placebo Other: Placebo Comparator
Placebo matched to atacicept injection will be administered subcutaneously twice weekly during initial loading period for 4 weeks followed by once weekly during maintenance period for subsequent 48 weeks.

  Eligibility

Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female 16 years of age or older
  • Disease history of at least six months meeting at least 4 out of the 11 American College of Rheumatology (ACR) criteria for SLE
  • Active SLE with at least one British Isles Lupus Assessment Group (BILAG) flare A or B at screening requiring a change in the dose of corticosteroids
  • Positive antinuclear antibody (ANA) or anti-double-stranded deoxyribonucleic acid (dsDNA) at screening
  • Female subjects must be willing to avoid pregnancy by using an adequate method of contraception for 4 weeks prior to Study Day 1, during the trial and 24 weeks after the last dose of study medication
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Active moderate to severe glomerulonephritis (kidney impairment) as defined in the protocol
  • Active central nervous system SLE deemed to be severe/progressive and/or associated with significant cognitive impairment leading to inability to provide informed consent and/or comply with the protocol
  • Previous treatment with rituximab, abatacept, or belimumab
  • History of demyelinating disease such as multiple sclerosis (MS) or optic neuritis
  • Other protocol defined exclusion criteria could 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: NCT00624338

  Hide Study Locations
Locations
United States, Alabama
Division of Clinical Immunology and Rheumatology - UAB
Birmingham, Alabama, United States, 35249-7201
United States, California
Stanford University
Palo Alto, California, United States
Research Site
San Diego, California, United States
Inland Rheumatology Clinical Trials Inc
Upland, California, United States
United States, Florida
Research Site
Jacksonville, Florida, United States
United States, Idaho
Research Site
Boise, Idaho, United States
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
US Local Medical Information
Rockland, Massachusetts, United States, 02370
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
Justus J. Fiechtner, MD, MPH
Lansing, Michigan, United States, 48910
United States, New York
SUNY Health Science Center at Brooklyn
Brooklyn, New York, United States
Feinstein Institute for Medical Research
Manhasset, New York, United States, 11030
Hospital for Special Surgey
New York, New York, United States, 10021
Research Site
New York, New York, United States
United States, Ohio
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Cincinnati, Ohio, United States
University of Cincinnati Medical Center, Division of Immunology
Cincinnati, Ohio, United States
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Temple, Texas, United States
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Virginia Mason Medical Center
Seattle, Washington, United States
Argentina
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Tucuman, Argentina
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Philippines
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Tula, Russian Federation
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Yaroslavl, Russian Federation
Serbia
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Belgrade, Serbia
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Niska Banja, Serbia
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South Africa
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Panorama, Western Cape, South Africa
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Stellenbosch, Western Cape, South Africa
Spain
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Santiago de Compostela, Spain
Switzerland
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St. Gallen, Switzerland
Taiwan
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Taichung, Taiwan
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Taoyuan, Taiwan
Ukraine
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Donetsk, Ukraine
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Kharkiv, Ukraine
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Lviv, Ukraine
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Vinnytsya, Ukraine
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Zhytomyr, Ukraine
United Kingdom
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London, United Kingdom
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Manchester, United Kingdom
Sponsors and Collaborators
EMD Serono
Merck KGaA
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00624338     History of Changes
Other Study ID Numbers: 27646 
Study First Received: February 15, 2008
Results First Received: January 19, 2016
Last Updated: March 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
Atacicept 75 and 150 mg
Placebo

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

ClinicalTrials.gov processed this record on August 23, 2016