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

February 15, 2008
March 11, 2016
January 2008
April 2012   (final data collection date for primary outcome measure)
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.
Proportion of patients experiencing a new flare as defined by a BILAG score of A or B during the 52 week treatment period [ Time Frame: Measures are monthly for 52 weeks, and at 24 weeks after last dose ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00624338 on ClinicalTrials.gov Archive Site
  • 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 ]
1- Time to new flare after randomization 2- Proportion of patients with new flare within the first 24 weeks after randomization [ Time Frame: Ad hoc and at 24 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (APRIL-SLE)
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)
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.
Not Provided
Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Lupus Erythematosus, Systemic
  • 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.
  • 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.
  • 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.
  • Experimental: Atacicept 75 mg
    Intervention: Drug: Atacicept 75 mg
  • Experimental: Atacicept 150 mg
    Intervention: Drug: Atacicept 150 mg
  • Placebo Comparator: Placebo
    Intervention: Other: Placebo Comparator
Isenberg D, Gordon C, Licu D, Copt S, Rossi CP, Wofsy D. Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial). Ann Rheum Dis. 2015 Nov;74(11):2006-15. doi: 10.1136/annrheumdis-2013-205067. Epub 2014 Jun 20. Erratum in: Ann Rheum Dis. 2016 May;75(5):946.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
461
October 2012
April 2012   (final data collection date for primary outcome measure)

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
Both
16 Years and older   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Bulgaria,   Croatia,   Czech Republic,   France,   Germany,   Greece,   India,   Israel,   Korea, Republic of,   Latvia,   Lebanon,   Lithuania,   Malaysia,   Mexico,   Netherlands,   Philippines,   Poland,   Russian Federation,   Serbia,   South Africa,   Spain,   Switzerland,   Taiwan,   Ukraine,   United Kingdom
 
NCT00624338
27646
Not Provided
Not Provided
Not Provided
EMD Serono
EMD Serono
Merck KGaA
Study Director: Medical Responsible Merck KGaA
EMD Serono
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP