Clinical trial NCT00624338: Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Lupus Erythematosus, Systemic
Keywords: Atacicept 75 and 150 mg
Placebo
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2008-02-27
Enrollment: 461
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants Experiencing a New Flare as Defined by British Isles Lupus Assessment Group (BILAG) Score A or B
timeFrame: From screening up to Week 52
Secondary outcomes:
measure: Time to First New Flare as Defined by BILAG Score A or B
timeFrame: From screening up to Week 52
measure: Percentage of Participants Experiencing a New Flare as Defined by BILAG Score A or B During Initial 24 Weeks
timeFrame: From screening up to Week 24
measure: Percentage of Participants Within Ordinal Response Categories for British Isles Lupus Assessment Group (BILAG) Flares
timeFrame: Week 52
measure: Mean Cumulative Corticosteroid Dose
timeFrame: Randomization up to Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Division of Clinical Immunology and Rheumatology - UAB
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials Inc
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Boise
country: United States
facility: Research Site
state: Idaho
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rockland
country: United States
facility: US Local Medical Information
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Lansing
country: United States
facility: Justus J. Fiechtner, MD, MPH
state: Michigan
city: Brooklyn
country: United States
facility: SUNY Health Science Center at Brooklyn
state: New York
city: Manhasset
country: United States
facility: Feinstein Institute for Medical Research
state: New York
city: New York
country: United States
facility: Hospital for Special Surgey
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center, Division of Immunology
state: Ohio
city: Temple
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Buenos Aires
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: Quilmes
country: Argentina
facility: Research Site
city: San Juan
country: Argentina
facility: Research Site
city: Tucuman
country: Argentina
facility: Research Site
city: Cairns
country: Australia
facility: Research Site
city: Clayton, Victoria
country: Australia
facility: Research Site
city: Sunshine Coast, Queensland
country: Australia
facility: Research Site
city: Woodville S.A.
country: Australia
facility: Research Site
city: Wein
country: Austria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Osijek
country: Croatia
facility: Research Site
city: Rijeka
country: Croatia
facility: Research Site
city: Split
country: Croatia
facility: Research Site
city: Zagreb
country: Croatia
facility: Research Site
city: Prague
country: Czech Republic
facility: Research Site
city: Bordeaux Pessac
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Montpelier Cedex
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Hanover
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Herne
country: Germany
facility: Research Site
city: Munchen
country: Germany
facility: Research Site
city: Munster
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Secunderabad, Andhra Pradesh
country: India
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerasalem
country: Israel
facility: Research Site
city: Petah-Tikva
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Beirut
country: Lebanon
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Vilnius
country: Lithuania
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Perak
country: Malaysia
facility: Research Site
city: Seremban
country: Malaysia
facility: Research Site
city: Guadalajara Jalisco
country: Mexico
facility: Research Site
city: Tijuana, BC
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Leiden
country: Netherlands
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Angeles City
country: Philippines
facility: Research Site
state: Pampanga
city: Davao
country: Philippines
facility: Research Site
city: Iloilo
country: Philippines
facility: Research Site
city: Las Pinas
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Torun
country: Poland
facility: Research Site
city: Warsawa
country: Poland
facility: Research Site
city: Kemerovo
country: Russian Federation
facility: Research Site
city: Petrozavodsk
country: Russian Federation
facility: Research Site
city: Ryazan
country: Russian Federation
facility: Research Site
city: Saratov
country: Russian Federation
facility: Research Site
city: St Petersburg
country: Russian Federation
facility: Research Site
city: Tula
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Niska Banja
country: Serbia
facility: Research Site
city: Novi Beograd
country: Serbia
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Panorama, Western Cape
country: South Africa
facility: Research Site
city: Parlow, Western Cape
country: South Africa
facility: Research Site
city: Pinelands
country: South Africa
facility: Research Site
city: Stellenbosch, Western Cape
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Donetsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Ternopil
country: Ukraine
facility: Research Site
city: Vinnytsya
country: Ukraine
facility: Research Site
city: Zhytomyr
country: Ukraine
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
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.