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

NCT ID: NCT00624338

Last Updated: 2016-03-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

461 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2012-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Lupus Erythematosus, Systemic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Atacicept 75 mg

Group Type EXPERIMENTAL

Atacicept 75 mg

Intervention Type DRUG

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.

Atacicept 150 mg

Group Type EXPERIMENTAL

Atacicept 150 mg

Intervention Type DRUG

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

Group Type PLACEBO_COMPARATOR

Placebo Comparator

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type OTHER

Eligibility Criteria

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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

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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

EMD Serono

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

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Research Site

Rijeka, , Croatia

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Division of Clinical Immunology and Rheumatology - UAB

Birmingham, Alabama, United States

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Stanford University

Palo Alto, California, United States

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San Diego, California, United States

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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

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Brigham and Women's Hospital

Boston, Massachusetts, United States

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US Local Medical Information

Rockland, Massachusetts, United States

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Wayne State University

Detroit, Michigan, United States

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Justus J. Fiechtner, MD, MPH

Lansing, Michigan, United States

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SUNY Health Science Center at Brooklyn

Brooklyn, New York, United States

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Feinstein Institute for Medical Research

Manhasset, New York, United States

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Hospital for Special Surgey

New York, New York, United States

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New York, New York, United States

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Cincinnati, Ohio, United States

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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

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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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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

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Countries

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United States Argentina Australia Austria Bulgaria Croatia Czechia France Germany Greece India Israel Latvia Lebanon Lithuania Malaysia Mexico Netherlands Philippines Poland Russia Serbia South Africa South Korea Spain Switzerland Taiwan Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 37332136 (View on PubMed)

Eslami 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.

Reference Type DERIVED
PMID: 36532058 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24951103 (View on PubMed)

Other Identifiers

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27646

Identifier Type: -

Identifier Source: org_study_id

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