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

Lupus Erythematosus, Systemic Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00624338
• Other study ID #: 27646
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 15, 2008
• Last updated: March 11, 2016
• Start date: January 2008
• Est. completion date: October 2012

Study information

• Verified date: March 2016
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 461
• Est. completion date: October 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic

Intervention

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.
• 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.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Cordoba
Argentina	Research Site	Quilmes
Argentina	Research Site	San Juan
Argentina	Research Site	Tucuman
Australia	Research Site	Cairns
Australia	Research Site	Clayton, Victoria
Australia	Research Site	Sunshine Coast, Queensland
Australia	Research Site	Woodville S.A.
Austria	Research Site	Wein
Bulgaria	Research Site	Sofia
Croatia	Research Site	Osijek
Croatia	Research Site	Rijeka
Croatia	Research Site	Split
Croatia	Research Site	Zagreb
Czech Republic	Research Site	Prague
France	Research Site	Bordeaux Pessac
France	Research Site	Lille
France	Research Site	Montpelier Cedex
France	Research Site	Paris
France	Research Site	Strasbourg
France	Research Site	Toulouse
Germany	Research Site	Berlin
Germany	Research Site	Erlangen
Germany	Research Site	Hanover
Germany	Research Site	Heidelberg
Germany	Research Site	Herne
Germany	Research Site	Munchen
Germany	Research Site	Munster
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
India	Research Site	Secunderabad, Andhra Pradesh
Israel	Research Site	Haifa
Israel	Research Site	Jerasalem
Israel	Research Site	Petah-Tikva
Israel	Research Site	Tel Aviv
Korea, Republic of	Research Site	Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Latvia	Research Site	Riga
Lebanon	Research Site	Beirut
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Vilnius
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Perak
Malaysia	Research Site	Seremban
Mexico	Research Site	Guadalajara Jalisco
Mexico	Research Site	Tijuana, BC
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Leiden
Netherlands	Research Site	Maastricht
Philippines	Research Site	Angeles City	Pampanga
Philippines	Research Site	Davao
Philippines	Research Site	Iloilo
Philippines	Research Site	Las Pinas
Philippines	Research Site	Manila
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Krakow
Poland	Research Site	Lublin
Poland	Research Site	Szczecin
Poland	Research Site	Torun
Poland	Research Site	Warsawa
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Petrozavodsk
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	St Petersburg
Russian Federation	Research Site	Tula
Russian Federation	Research Site	Yaroslavl
Serbia	Research Site	Belgrade
Serbia	Research Site	Niska Banja
Serbia	Research Site	Novi Beograd
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Panorama, Western Cape
South Africa	Research Site	Parlow, Western Cape
South Africa	Research Site	Pinelands
South Africa	Research Site	Stellenbosch, Western Cape
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Santiago de Compostela
Switzerland	Research Site	St. Gallen
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Ukraine	Research Site	Donetsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Ternopil
Ukraine	Research Site	Vinnytsya
Ukraine	Research Site	Zhytomyr
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Division of Clinical Immunology and Rheumatology - UAB	Birmingham	Alabama
United States	Research Site	Boise	Idaho
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	SUNY Health Science Center at Brooklyn	Brooklyn	New York
United States	Research Site	Cincinnati	Ohio
United States	University of Cincinnati Medical Center, Division of Immunology	Cincinnati	Ohio
United States	Wayne State University	Detroit	Michigan
United States	Research Site	Jacksonville	Florida
United States	Justus J. Fiechtner, MD, MPH	Lansing	Michigan
United States	Feinstein Institute for Medical Research	Manhasset	New York
United States	Hospital for Special Surgey	New York	New York
United States	Research Site	New York	New York
United States	Stanford University	Palo Alto	California
United States	US Local Medical Information	Rockland	Massachusetts
United States	Research Site	San Diego	California
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Research Site	Temple	Texas
United States	Inland Rheumatology Clinical Trials Inc	Upland	California

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono	Merck KGaA

Countries where clinical trial is conducted

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	From screening up to Week 52	No
Secondary	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.	From screening up to Week 24	No
Secondary	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.	Week 52	No
Secondary	Mean Cumulative Corticosteroid Dose		Randomization up to Week 52	No