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

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ClinicalTrials.gov Identifier: NCT00624338
Recruitment Status : Completed
First Posted : February 27, 2008
Results First Posted : March 14, 2016
Last Update Posted : March 14, 2016
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
Lupus Erythematosus, Systemic Drug: Atacicept 75 mg Drug: Atacicept 150 mg Other: Placebo Comparator Phase 2 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 461 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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)
Study Start Date : January 2008
Actual Primary Completion Date : April 2012
Actual Study Completion Date : October 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Time to First New Flare as Defined by BILAG Score A or B [ Time Frame: From screening up to Week 52 ]
    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.

  2. 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 ]
    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.

  3. Percentage of Participants Within Ordinal Response Categories for British Isles Lupus Assessment Group (BILAG) Flares [ Time Frame: Week 52 ]
    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.

  4. Mean Cumulative Corticosteroid Dose [ Time Frame: Randomization up to Week 52 ]

Eligibility Criteria
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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00624338


Locations
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Sponsors and Collaborators
EMD Serono
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00624338    
Other Study ID Numbers: 27646
First Posted: February 27, 2008    Key Record Dates
Results First Posted: March 14, 2016
Last Update Posted: March 14, 2016
Last Verified: March 2016
Keywords provided by EMD Serono:
Atacicept 75 and 150 mg
Placebo
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases