Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (APRIL-SLE) (APRIL-SLE)
Primary Purpose
Lupus Erythematosus, Systemic
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Atacicept 75 mg
Atacicept 150 mg
Placebo Comparator
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Erythematosus, Systemic focused on measuring Atacicept 75 and 150 mg, Placebo
Eligibility 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
Sites / Locations
- Division of Clinical Immunology and Rheumatology - UAB
- Stanford University
- Research Site
- Inland Rheumatology Clinical Trials Inc
- Research Site
- Research Site
- Brigham and Women's Hospital
- US Local Medical Information
- Wayne State University
- Justus J. Fiechtner, MD, MPH
- SUNY Health Science Center at Brooklyn
- Feinstein Institute for Medical Research
- Hospital for Special Surgey
- Research Site
- Research Site
- University of Cincinnati Medical Center, Division of Immunology
- Research Site
- Virginia Mason Medical Center
- Research Site
- Research Site
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Atacicept 75 mg
Atacicept 150 mg
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants Experiencing a New Flare as Defined by British Isles Lupus Assessment Group (BILAG) Score A or B
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
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
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
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
Full Information
NCT ID
NCT00624338
First Posted
February 15, 2008
Last Updated
March 11, 2016
Sponsor
EMD Serono
Collaborators
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT00624338
Brief Title
Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (APRIL-SLE)
Acronym
APRIL-SLE
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 Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
October 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono
Collaborators
Merck KGaA, Darmstadt, Germany
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Systemic
Keywords
Atacicept 75 and 150 mg, Placebo
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
461 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Atacicept 75 mg
Arm Type
Experimental
Arm Title
Atacicept 150 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Atacicept 75 mg
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Atacicept 150 mg
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo Comparator
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing a New Flare as Defined by British Isles Lupus Assessment Group (BILAG) Score A or B
Description
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.
Time Frame
From screening up to Week 52
Secondary Outcome Measure Information:
Title
Time to First New Flare as Defined by BILAG Score A or B
Description
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.
Time Frame
From screening up to Week 52
Title
Percentage of Participants Experiencing a New Flare as Defined by BILAG Score A or B During Initial 24 Weeks
Description
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.
Time Frame
From screening up to Week 24
Title
Percentage of Participants Within Ordinal Response Categories for British Isles Lupus Assessment Group (BILAG) Flares
Description
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.
Time Frame
Week 52
Title
Mean Cumulative Corticosteroid Dose
Time Frame
Randomization up to Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Division of Clinical Immunology and Rheumatology - UAB
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249-7201
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
Country
United States
Facility Name
Research Site
City
San Diego
State/Province
California
Country
United States
Facility Name
Inland Rheumatology Clinical Trials Inc
City
Upland
State/Province
California
Country
United States
Facility Name
Research Site
City
Jacksonville
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Boise
State/Province
Idaho
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
US Local Medical Information
City
Rockland
State/Province
Massachusetts
ZIP/Postal Code
02370
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Justus J. Fiechtner, MD, MPH
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48910
Country
United States
Facility Name
SUNY Health Science Center at Brooklyn
City
Brooklyn
State/Province
New York
Country
United States
Facility Name
Feinstein Institute for Medical Research
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Hospital for Special Surgey
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
University of Cincinnati Medical Center, Division of Immunology
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Temple
State/Province
Texas
Country
United States
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
Country
United States
Facility Name
Research Site
City
Buenos Aires
Country
Argentina
Facility Name
Research Site
City
Cordoba
Country
Argentina
Facility Name
Research Site
City
Quilmes
Country
Argentina
Facility Name
Research Site
City
San Juan
Country
Argentina
Facility Name
Research Site
City
Tucuman
Country
Argentina
Facility Name
Research Site
City
Cairns
Country
Australia
Facility Name
Research Site
City
Clayton, Victoria
Country
Australia
Facility Name
Research Site
City
Sunshine Coast, Queensland
Country
Australia
Facility Name
Research Site
City
Woodville S.A.
Country
Australia
Facility Name
Research Site
City
Wein
Country
Austria
Facility Name
Research Site
City
Sofia
Country
Bulgaria
Facility Name
Research Site
City
Osijek
Country
Croatia
Facility Name
Research Site
City
Rijeka
Country
Croatia
Facility Name
Research Site
City
Split
Country
Croatia
Facility Name
Research Site
City
Zagreb
Country
Croatia
Facility Name
Research Site
City
Prague
Country
Czech Republic
Facility Name
Research Site
City
Bordeaux Pessac
Country
France
Facility Name
Research Site
City
Lille
Country
France
Facility Name
Research Site
City
Montpelier Cedex
Country
France
Facility Name
Research Site
City
Paris
Country
France
Facility Name
Research Site
City
Strasbourg
Country
France
Facility Name
Research Site
City
Toulouse
Country
France
Facility Name
Research Site
City
Berlin
Country
Germany
Facility Name
Research Site
City
Erlangen
Country
Germany
Facility Name
Research Site
City
Hanover
Country
Germany
Facility Name
Research Site
City
Heidelberg
Country
Germany
Facility Name
Research Site
City
Herne
Country
Germany
Facility Name
Research Site
City
Munchen
Country
Germany
Facility Name
Research Site
City
Munster
Country
Germany
Facility Name
Research Site
City
Athens
Country
Greece
Facility Name
Research Site
City
Thessaloniki
Country
Greece
Facility Name
Research Site
City
Secunderabad, Andhra Pradesh
Country
India
Facility Name
Research Site
City
Haifa
Country
Israel
Facility Name
Research Site
City
Jerasalem
Country
Israel
Facility Name
Research Site
City
Petah-Tikva
Country
Israel
Facility Name
Research Site
City
Tel Aviv
Country
Israel
Facility Name
Research Site
City
Gyeonggi-do
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
Country
Korea, Republic of
Facility Name
Research Site
City
Riga
Country
Latvia
Facility Name
Research Site
City
Beirut
Country
Lebanon
Facility Name
Research Site
City
Kaunas
Country
Lithuania
Facility Name
Research Site
City
Vilnius
Country
Lithuania
Facility Name
Research Site
City
Kuala Lumpur
Country
Malaysia
Facility Name
Research Site
City
Perak
Country
Malaysia
Facility Name
Research Site
City
Seremban
Country
Malaysia
Facility Name
Research Site
City
Guadalajara Jalisco
Country
Mexico
Facility Name
Research Site
City
Tijuana, BC
Country
Mexico
Facility Name
Research Site
City
Amsterdam
Country
Netherlands
Facility Name
Research Site
City
Leiden
Country
Netherlands
Facility Name
Research Site
City
Maastricht
Country
Netherlands
Facility Name
Research Site
City
Angeles City
State/Province
Pampanga
Country
Philippines
Facility Name
Research Site
City
Davao
Country
Philippines
Facility Name
Research Site
City
Iloilo
Country
Philippines
Facility Name
Research Site
City
Las Pinas
Country
Philippines
Facility Name
Research Site
City
Manila
Country
Philippines
Facility Name
Research Site
City
Bialystok
Country
Poland
Facility Name
Research Site
City
Gdańsk
Country
Poland
Facility Name
Research Site
City
Krakow
Country
Poland
Facility Name
Research Site
City
Lublin
Country
Poland
Facility Name
Research Site
City
Szczecin
Country
Poland
Facility Name
Research Site
City
Torun
Country
Poland
Facility Name
Research Site
City
Warsawa
Country
Poland
Facility Name
Research Site
City
Kemerovo
Country
Russian Federation
Facility Name
Research Site
City
Petrozavodsk
Country
Russian Federation
Facility Name
Research Site
City
Ryazan
Country
Russian Federation
Facility Name
Research Site
City
Saratov
Country
Russian Federation
Facility Name
Research Site
City
St Petersburg
Country
Russian Federation
Facility Name
Research Site
City
Tula
Country
Russian Federation
Facility Name
Research Site
City
Yaroslavl
Country
Russian Federation
Facility Name
Research Site
City
Belgrade
Country
Serbia
Facility Name
Research Site
City
Niska Banja
Country
Serbia
Facility Name
Research Site
City
Novi Beograd
Country
Serbia
Facility Name
Research Site
City
Cape Town
Country
South Africa
Facility Name
Research Site
City
Durban
Country
South Africa
Facility Name
Research Site
City
Panorama, Western Cape
Country
South Africa
Facility Name
Research Site
City
Parlow, Western Cape
Country
South Africa
Facility Name
Research Site
City
Pinelands
Country
South Africa
Facility Name
Research Site
City
Stellenbosch, Western Cape
Country
South Africa
Facility Name
Research Site
City
Barcelona
Country
Spain
Facility Name
Research Site
City
Madrid
Country
Spain
Facility Name
Research Site
City
Malaga
Country
Spain
Facility Name
Research Site
City
Santiago de Compostela
Country
Spain
Facility Name
Research Site
City
St. Gallen
Country
Switzerland
Facility Name
Research Site
City
Taichung
Country
Taiwan
Facility Name
Research Site
City
Taipei
Country
Taiwan
Facility Name
Research Site
City
Taoyuan
Country
Taiwan
Facility Name
Research Site
City
Donetsk
Country
Ukraine
Facility Name
Research Site
City
Kharkiv
Country
Ukraine
Facility Name
Research Site
City
Kyiv
Country
Ukraine
Facility Name
Research Site
City
Lviv
Country
Ukraine
Facility Name
Research Site
City
Ternopil
Country
Ukraine
Facility Name
Research Site
City
Vinnytsya
Country
Ukraine
Facility Name
Research Site
City
Zhytomyr
Country
Ukraine
Facility Name
Research Site
City
London
Country
United Kingdom
Facility Name
Research Site
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
24951103
Citation
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.
Results Reference
derived
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Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (APRIL-SLE)
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