Efficacy and Safety of Atacicept in Systemic Lupus Erythematosus

Lupus Erythematosus, Systemic Clinical Trial

— ADDRESS II  

Official title:

A Phase IIb, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multidose, 24-Week Study to Evaluate the Efficacy and Safety of Atacicept in Subjects With Systemic Lupus Erythematosus (SLE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01972568
• Other study ID #: 700461-023
• Secondary ID: 2013-002773-21
• Status: Completed
• Phase: Phase 2
• First received: October 24, 2013
• Last updated: December 4, 2017
• Start date: December 2013
• Est. completion date: September 2016

Study information

• Verified date: December 2017
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, double-blind, randomized, Phase 2b trial to evaluate the efficacy of atacicept in subjects with systemic lupus erythematosus (SLE).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 306
• Est. completion date: September 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Eligible male and female subjects, aged 18 years or older

• Must have at least moderately active SLE, as defined as SLE Disease Activity Index-2000 (SLEDAI-2K) score greater than or equal to [>=] 6 at screening visit

• At least 4 of the 11 American college of rheumatology (ACR) classification criteria for SLE (diagnosed >= 6 months prior to the screening visit)

• Be seropositive for anti-nuclear antibodies (ANA) and/or anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Subjects have demyelinating disorder

• Severe central nervous system SLE

• Use of cyclophosphamide within 3 months of the screening visit

• Urine protein:creatinine ratio (UPCr) >= 2 milligram per milligram (mg/mg) per day

• Other protocol defined exclusion criteria could apply

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic

Intervention

Drug:
• Atacicept 75 milligram (mg)
Atacicept 75 mg will be administered as subcutaneous injection once weekly for 24 weeks.
• Atacicept 150 mg
Atacicept 150 mg will be administered as subcutaneous injection once weekly for 24 weeks.
• Placebo
Placebo matched to atacicept will be administered as subcutaneous injection once weekly for 24 weeks.

Locations

Country	Name	City	State
Argentina	APRILLUS	Ciudad Autonoma Buenos aires
Argentina	Atencion Integral en Reumatologia (AIR)	Ciudad Autonoma Buenos Aires
Argentina	Hospital Italiano	Ciudad Autonoma Buenos Aires
Argentina	Organizacion Medica de Investigacion (OMI)	Ciudad Autonoma Buenos Aires
Argentina	Policlìnica Red Omip S.A - Ensayos Clinicos GC	Mar De Plata
Argentina	Centro de Investigacion Pergamino SA	Pergamino
Argentina	Cordis S.A.	Salta
Argentina	Centro Polivalente de Asistencia e Inv. Clinica CER	San Juan
Argentina	Centro Medico Privado de Reumatologia	San Miguel de Tucuman
Argentina	Investigaciones Clinicas Tucuman	San Miguel de Tucuman
Argentina	Centro Integral de Reumatologia	San Miguel de Tucumán
Brazil	CPD - Centro de Pesquisas em Diabetes	Porto Alegre
Brazil	CLION - Clínica de Oncologia da Bahia	Salvador
Brazil	Clínica de Neoplasias Litoral Ltda.	Santa Catarina
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto
Bulgaria	MHAT "Eurohospital" - Plovdiv, OOD	Plovdiv
Bulgaria	Medical Center "Teodora", EOOD	Ruse
Bulgaria	DCC "Sveta Anna", EOOD	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski", EAD	Sofia
Bulgaria	Medical Center "Nov Rehabilitatsionen Tsentar", EOOD	Stara Zagora
Bulgaria	MHAT-Targovishte, AD	Targovishte
Chile	Biomedica	Santiago
Chile	Centro de Estudios Reumatologicos	Santiago
Chile	Centro Medico Prosalud	Santiago
Chile	SOMEAL	Santiago
Chile	CINVEC - Centro de Investigacion Clinica V Region	Vina del Mar
Czechia	A-Shine, s.r.o.	Plzen
Czechia	Revmatologicky Ustav	Praha 2
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	MEDICAL PLUS s.r.o.	Uherske Hradiste
Germany	Kerckhoff-Klinik gGmbH	Bad Nauheim
Germany	Charite Universitaetsmedizin Berlin - Campus Charite Mitte	Berlin
Germany	Klinikum der Johann Wolfgang Goethe-Universitaet	Frankfurt
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Rheumazentrum Ruhrgebiet	Herne
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Kiel	Kiel
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz
Italy	Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari	Bari
Italy	Presidio Ospedaliero Vittorio Emanuele	Catania
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Azienda Ospedaliero Universitaria San Martino	Genova
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Japan	St. Luke's International Hospital	Chuo-ku
Japan	NHO Kyushu Medical Center	Fukuoka-shi
Japan	Toho University Ohashi Medical Center	Meguro-ku
Japan	Okayama University Hospital	Okayama-shi
Japan	Kitasato University Hospital	Sagamihara-shi
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	Sapporo City General Hospital	Sapporo-shi
Japan	Hakujujikai Sasebochuo Hospital	Sasebo-shi
Japan	Tohoku University Hospital	Sendai-shi
Japan	Jichi Medical University Hospital	Shimotsuke-shi
Japan	National Center for Global Health and Medicine Hospital	Shinjuku
Japan	Yuaikai Tomishiro Chuo Hospital	Tomigusuku-shi
Japan	Tsukuba University Hospital	Tsukuba-shi
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si
Mexico	Investigacion y Biomedicina de Chihuahua, S.C.	Chihuahua
Mexico	Icle S.C.	Guadalajara
Mexico	Unidad de Investigacion en Enfermedades Cronico Degenerativas SC	Guadalajara
Mexico	Investigacion Clinica de Leon S.C.	Leon
Mexico	Morales Vargas Centro de Investigacion, S.C.	Leon
Mexico	Centro de Estudios Clinicos Especializados	Merida
Mexico	Accelerium S. de R.L. de C.V.	Monterrey
Mexico	ALIVIA Clínica de Alta Especialidad S.A. de C.V.	Monterrey
Mexico	Clinica de Enfermedades Cronicas y de Procedimientos Especiales, S.C.	Morelia
Mexico	Hospital Universitario de Saltillo "Dr. Gonzalo Valdés Valdés"	Saltillo
Peru	Clinica El Golf	Lima
Peru	Clinica Medica Cayetano Heredia	Lima
Peru	Clinica Vesalio	Lima
Peru	HMA - Hospital Maria Auxiliadora	Lima
Philippines	Angeles University Foundation Medical Center	Angeles City
Philippines	Mary Mediatrix Medical Center	Batangas
Philippines	Davao Doctors Hospital	Davao City
Philippines	Iloilo Doctors Hospital	Iloilo City
Philippines	St. Luke's Medical Center	Quezon City
Poland	Szpital Uniwersytecki nr 2 im.dr J. Biziela	Bydgoszcz
Poland	Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z	Torun
Poland	Rheuma Medicus Zaklad Opieki Zdrowotnej	Warsaw
Poland	Wojskowy Instytut Medyczny	Warszawa
Russian Federation	SBEI HPE Altai State Medical University of MoH and SD	Barnaul
Russian Federation	SBHI of Kem. "Regional Clinical Hospital for War Veterans"	Kemerovo
Russian Federation	First Moscow State Medical University n.a. I.M. Sechenov	Moscow
Russian Federation	Municipal City Hospital #2	Omsk
Russian Federation	Republican Hospital n.a. V.A. Baranov	Petrozavodsk
Russian Federation	City Clinical Hospital #12	Saratov
Russian Federation	Regional Clinical Hospital	Saratov
Russian Federation	Clinical Rheumatology Hospital #25	St. Petersburg
Russian Federation	Out - patient Clinic # 107	St. Petersburg
Russian Federation	Regional Clinical Hospital	Vladimir
Russian Federation	Yaroslavl State Medical University	Yaroslavl
South Africa	Dr CE Spargo and Dr RB Bhorat	Cape Town
South Africa	Naidoo, A	Durban
South Africa	Winelands Medical Research Centre	Stellenbosch
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital de Sagunto	Sagunto
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
United Kingdom	Royal National Hospital for Rheumatic Diseases	Bath
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Guy's Hospital	London
United Kingdom	University College London Hospitals	London
United Kingdom	Wrightington Hospital	Wigan
United States	Southern California Permanente Medical Group	Anaheim	California
United States	Pinnacle Research Group LLC	Anniston	Alabama
United States	Achieve Clinical Research, LLC	Birmingham	Alabama
United States	University of Alabama at Birmingham - (UAB)	Birmingham	Alabama
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Box Arthritis & Rheumatology of the Carolinas PLLC	Charlotte	North Carolina
United States	MetroHealth System	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Danville Orthopedic Clinic, Inc.	Danville	Virginia
United States	STAT Research, Inc.	Dayton	Ohio
United States	Clinical Research of West Florida - Corporate	Dunedin	Florida
United States	Center for Rheumatology, Immunology & Arthritis	Fort Lauderdale	Florida
United States	UTMB Pathology Clinical Services	Galveston	Texas
United States	AA MRC LLC Ahmed Arif Medical Research Center	Grand Blanc	Michigan
United States	Goldpoint Clinical Research, LLC	Indianapolis	Indiana
United States	Wallace Rheumatic Study Center	Los Angeles	California
United States	The Feinstein Institute for Medical Research	Manhasset	New York
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Hospital for Special Surgery	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Arthritis & Rheumatology Center of Oklahoma	Oklahoma City	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	OMRF	Oklahoma City	Oklahoma
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	East Bay Rheumatology Medical Group, Inc.	San Leandro	California
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	North MS Medical Clinics, Inc.	Tupelo	Mississippi
United States	Arthritis & Osteoporosis Clinic	Waco	Texas
United States	Clinical Research Center of Reading LLC	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Chile,  Czechia,  Germany,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Philippines,  Poland,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline	SRI response, a composite measure of reduced SLE disease activity, was defined as a reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points; no significant worsening in Physician's Global Assessment (PGA) score (<10 % increase, defined as <0.3 point increase for statistical analyses); no new British Isles Lupus Assessment Group (BILAG) A organ domain scores and <=1 (defined as no more than one) new BILAG B organ domain score.	Week 24
Primary	Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Day 1 as Baseline	SRI response, a composite measure of reduced SLE disease activity, was defined as a reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points; no significant worsening in Physician's Global Assessment (PGA) score (<10 % increase, defined as <0.3 point increase for statistical analyses); no new British Isles Lupus Assessment Group (BILAG) A organ domain scores and <=1 (defined as no more than one) new BILAG B organ domain score.	Week 24
Secondary	Percentage of Subjects at Week 24 Whose Prednisone-Equivalent Corticosteroid (CS) Dose Reduced From Screening by >=25% and to a Dose of =<7.5mg/Day, and no British Isles Lupus Assessment Group (BILAG) A or 2B Flare in Disease Activity	BILAG A or 2B flare is defined by 1 new BILAG A organ domain score and/or 2 new BILAG B organ domain scores compared to the Screening Visit. 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 >20 mg daily or immunosuppressants); BILAG B: moderate disease activity requiring treatment with systemic low-dose oral glucocorticoids, intramuscular or intra-articular or soft tissue CS injection, topical CS or immunosuppressants, or symptomatic therapy such as antimalarials or NSAIDs. BILAG C: mild disease; BILAG D: system previously affected but now inactive and BILAG E: system never involved.	Week 24
Secondary	Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24	The PGIC is self-rated scale that asks the subject to describe the change in activity limitations, symptoms, emotions, and overall Quality of life (QoL) related to the subject's painful condition on the following scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). Percentage of subjects in the PGIC categories of very much or much improved (1 or 2), minimally improved or no change or minimally worse (3 or 4 or 5) and much or very much worse (6 or 7) at Week 24 were presented.	Week 24
Secondary	Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24	Change From screening visit to Week 24 of prednisolone-equivalent CS daily dose was presented.	Screening and Week 24
Secondary	Time From Randomization to First SRI Response During Treatment Period	SRI response, a composite measure of reduced SLE disease activity, was defined as a reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points; no significant worsening in Physician's Global Assessment (PGA) score (<10 % increase, defined as <0.3 point increase for statistical analyses); no new British Isles Lupus Assessment Group (BILAG) A organ domain scores and <=1 (defined as no more than one) new BILAG B organ domain score. Time to first SRI response during treatment period was presented.	Baseline up to 24 Weeks
Secondary	Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24	The BICLA response is defined as BILAG-2004 improvement (all screening visit BILAG A improving to B/C/D, all screening visit BILAG B to C/D, and <=1 new BILAG B and no new BILAG A); no deterioration in SLEDAI total score; PGA increase by <10% (defined as <0.3 point increase for the statistical analyses) and no nonpermitted medication/treatment.	Week 24
Secondary	Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 48 weeks. TEAEs include both Serious TEAEs and non-serious TEAEs.	Baseline up to 24 weeks after last dose of study drug (assessed up to maximum of 48 weeks)
Secondary	Change From Week 0 (Day 1) in SF-36 Components at Week 24	The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component summary scores. Total of 10 variables were analyzed (8 aspects, 2 component summary scores). The score for each of the 8 aspects and 2 component summary scores was scaled from 0 to 100, where 0 = lowest level of functioning and 100 = highest level of functioning.	Week 0 (Day 1) and Week 24