Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (APRIL-SLE)
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)
1 other identifier
interventional
461
28 countries
112
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2008
Longer than P75 for phase_2
112 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2008
CompletedFirst Submitted
Initial submission to the registry
February 15, 2008
CompletedFirst Posted
Study publicly available on registry
February 27, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2012
CompletedResults Posted
Study results publicly available
March 14, 2016
CompletedMarch 14, 2016
March 1, 2016
4.3 years
February 15, 2008
January 19, 2016
March 11, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
From screening up to Week 52
Secondary Outcomes (4)
Time to First New Flare as Defined by BILAG Score A or B
From screening up to Week 52
Percentage of Participants Experiencing a New Flare as Defined by BILAG Score A or B During Initial 24 Weeks
From screening up to Week 24
Percentage of Participants Within Ordinal Response Categories for British Isles Lupus Assessment Group (BILAG) Flares
Week 52
Mean Cumulative Corticosteroid Dose
Randomization up to Week 52
Study Arms (3)
Atacicept 75 mg
EXPERIMENTALAtacicept 150 mg
EXPERIMENTALPlacebo
PLACEBO COMPARATORInterventions
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.
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 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 Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- EMD Seronolead
- Merck KGaA, Darmstadt, Germanycollaborator
Study Sites (113)
Division of Clinical Immunology and Rheumatology - UAB
Birmingham, Alabama, 35249-7201, United States
Stanford University
Palo Alto, California, United States
Research Site
San Diego, California, United States
Inland Rheumatology Clinical Trials Inc
Upland, California, United States
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Jacksonville, Florida, United States
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Boise, Idaho, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
US Local Medical Information
Rockland, Massachusetts, 02370, United States
Wayne State University
Detroit, Michigan, 48201, United States
Justus J. Fiechtner, MD, MPH
Lansing, Michigan, 48910, United States
SUNY Health Science Center at Brooklyn
Brooklyn, New York, United States
Feinstein Institute for Medical Research
Manhasset, New York, 11030, United States
Hospital for Special Surgey
New York, New York, 10021, United States
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New York, New York, United States
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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
Virginia Mason Medical Center
Seattle, Washington, United States
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Buenos Aires, Argentina
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Córdoba, Argentina
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Quilmes, Argentina
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San Juan, Argentina
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San Miguel de Tucumán, Argentina
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Cairns, Australia
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Clayton, Victoria, Australia
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Sunshine Coast, Queensland, Australia
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Woodville S.A., Australia
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Wein, Austria
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Sofia, Bulgaria
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Osijek, Croatia
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Rijeka, Croatia
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Split, Croatia
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Zagreb, Croatia
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Prague, Czechia
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Bordeaux Pessac, France
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Lille, France
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Montpelier Cedex, France
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Paris, France
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Strasbourg, France
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Toulouse, France
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Berlin, Germany
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Erlangen, Germany
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Hanover, Germany
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Heidelberg, Germany
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Herne, Germany
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München, Germany
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Münster, Germany
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Athens, Greece
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Thessaloniki, Greece
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Secunderabad, Andhra Pradesh, India
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Haifa, Israel
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Jerasalem, Israel
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Petah Tikva, Israel
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Tel Aviv, Israel
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Riga, Latvia
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Beirut, Lebanon
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Kaunas, Lithuania
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Vilnius, Lithuania
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Kuala Lumpur, Malaysia
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Perak, Malaysia
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Seremban, Malaysia
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Guadalajara Jalisco, Mexico
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Tijuana, BC, Mexico
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Amsterdam, Netherlands
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Leiden, Netherlands
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Maastricht, Netherlands
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Angeles City, Pampanga, Philippines
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Davao City, Philippines
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Iloilo City, Philippines
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Las Piñas, Philippines
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Manila, Philippines
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Bialystok, Poland
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Gdansk, Poland
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Krakow, Poland
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Lublin, Poland
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Szczecin, Poland
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Torun, Poland
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Warsaw, Poland
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Kemerovo, Russia
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Petrozavodsk, Russia
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Ryazan, Russia
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Saint Petersburg, Russia
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Saratov, Russia
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Tula, Russia
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Yaroslavl, Russia
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Belgrade, Serbia
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New Belgrade, Serbia
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Niška Banja, Serbia
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Cape Town, South Africa
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Durban, South Africa
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Panorama, Western Cape, South Africa
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Parlow, Western Cape, South Africa
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Pinelands, South Africa
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Stellenbosch, Western Cape, South Africa
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Gyeonggi-do, South Korea
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Seoul, South Korea
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Barcelona, Spain
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Madrid, Spain
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Málaga, Spain
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Santiago de Compostela, Spain
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Sankt Gallen, Switzerland
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Taichung, Taiwan
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Taipei, Taiwan
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Taoyuan District, Taiwan
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Donetsk, Ukraine
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Kharkiv, Ukraine
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Kyiv, Ukraine
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Lviv, Ukraine
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Ternopil, Ukraine
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Vinnytsia, Ukraine
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Zhytomyr, Ukraine
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London, United Kingdom
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Manchester, United Kingdom
Related Publications (3)
Pitsiu M, Yalkinoglu O, Farrell C, Girard P, Vazquez-Mateo C, Papasouliotis O. Population pharmacokinetics of atacicept in systemic lupus erythematosus: An analysis of three clinical trials. CPT Pharmacometrics Syst Pharmacol. 2023 Aug;12(8):1157-1169. doi: 10.1002/psp4.12982. Epub 2023 Jun 18.
PMID: 37332136DERIVEDEslami M, Willen D, Papasouliotis O, Schuepbach-Mallpell S, Willen L, Donze O, Yalkinoglu O, Schneider P. Kinetics of free and ligand-bound atacicept in human serum. Front Immunol. 2022 Dec 2;13:1035556. doi: 10.3389/fimmu.2022.1035556. eCollection 2022.
PMID: 36532058DERIVEDIsenberg 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.
PMID: 24951103DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Atacicept 150 mg group was discontinued on 2 February 2011 based on the recommendation from the Independent Data Monitoring Committee.
Results Point of Contact
- Title
- Merck KGaA Communication Center
- Organization
- Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Study Officials
- STUDY DIRECTOR
Medical Responsible
Merck KGaA, Darmstadt, Germany
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 15, 2008
First Posted
February 27, 2008
Study Start
January 1, 2008
Primary Completion
April 1, 2012
Study Completion
October 1, 2012
Last Updated
March 14, 2016
Results First Posted
March 14, 2016
Record last verified: 2016-03