Long-term Safety and Tolerability of Atacicept (Long-term Follow-Up of Participant Who Participated in ADDRESS II)
- Conditions
- Lupus Erythematosus, Systemic
- Interventions
- Registration Number
- NCT02070978
- Lead Sponsor
- EMD Serono
- Brief Summary
This is a multicenter, double-blind, Phase 2b, long-term extension (LTE) to the ADDRESS II core trial (EMR 700461-023) (NCT01972568), to evaluate long-term safety and tolerability of atacicept in participants with systemic lupus erythematosus (SLE). Participants who completed the 24-week core study ADDRESS II core study (NCT01972568) and thus not met any of the discontinuation criteria were invited to enter this long-term extension (LTE) study NCT02070978.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 253
- Participants who had completed the 24-week treatment period of study EMR-700461-023 (ADDRESS II core trial)
- Women of childbearing potential who had a negative pregnancy test
- Other protocol defined inclusion criteria were applied
- Active neurological symptoms of SLE that were deemed severe or progressive
- Diagnosis of any demyelinating disease, such as, but not restricted to, multiple sclerosis (MS) or optic neuritis
- Pregnancy
- Active clinically significant viral, bacterial, or fungal infection, or any major episode of infection that in the investigator's opinion makes the participants unsuitable to continued participation in the study
- Other protocol defined exclusion criteria were applied
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atacicept 150 mg Atacicept 150 mg - Placebo/Atacicept 150 mg Atacicept 150 mg - Atacicept 75 mg Atacicept 75 mg -
- Primary Outcome Measures
Name Time Method Number of Participants With at Least One Serious Adverse Event (SAE) During the Treatment Period Baseline (LTE Day 1) up to maximum treatment duration of 143.7 weeks An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) 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. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. Treatment- Emergent adverse events (TEAEs) during the treatment period exclude those ongoing at the time of study entry into 024 LTE Day 1 and exclude the safety follow-up period.
Number of Participants Who Prematurely Discontinued the Treatment Due to Adverse Event (AE) Baseline (Day 1 of Core study) up to maximum duration of 167.7 weeks An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. TEAEs were defined as events with an onset date on or after the date of first dose of study treatment in the core study and ongoing at the 024 LTE study entry, occurring during the 024 LTE study and the Safety follow-up Period.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score Baseline: Core study Screening, LTE Day 1, Week 24, Week 48, Week 72 and Week 96 BILAG Disease Activity Index evaluates systemic lupus erythematosus (SLE) activity in 8 organ system domains: General, mucocutaneous, neurological, musculoskeletal, cardiorespiratory, vasculitis, renal, and hematologic using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Severe disease activity; BILAG B: moderate disease activity; BILAG C: mild disease; BILAG D: system previously affected but now inactive; BILAG E: system never involved. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). The total BILAG score is the sum of the scores of the 8 domains where A=9, B=3, C=1, D=0, and E=0. The total score ranges from 0 to 72 with a higher score indicating greater lupus activity.
Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores Baseline: Day 1 (Core Study), Day 1 (LTE Study), Week 24, Week 48, Week 72 and Week 96 SLICC/ACR score or damage index evaluates cumulative damage in Systemic Lupus Erythematosus (SLE). These changes may or may not be related to SLE. Most items are scored only if they have been present for at least 6 months. Scores range from 0 to 47 points, with higher scores indicating greater cumulative damage. Baseline was defined as Day 1 of Core study.
Change From Baseline in Disease Activity as Measured by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96 SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). Baseline was defined as core study screening visit.
Change From Baseline in Disease Activity as Measured by SLEDAI-2K Responder Index-50 (SRI-50) Score Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96 SRI-50 index was derived from SLEDAI-2K and could capture 50% or better improvement in each descriptor between any 2 visits in systemic lupus erythematosus (SLE) participants when there was incomplete resolution. The new assigned scores for the descriptors of SRI-50 were derived by dividing the score of each SLEDAI-2K descriptor by 2. SLEDAI-2K was an activity index that measured disease activity and records feature of active lupus as present or not present. SLEDAI-2K used a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present was assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranged from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score Baseline: Screening Visit (Core Study); LTE Day1, Week 24, Week 48, Week 72 and Week 96 The PGA was used to quantify disease activity and was measured using an anchored visual analog scale (VAS). The participant's current disease activity assessed by investigator in the score range of 0 to 3. Where 0=none; 1=mild; 2=moderate; 3=severe. The assessment made relative not to the participant's most severe state, but the most severe state of systemic lupus erythematosus (SLE) per the investigator's assessment. Baseline was defined as core study screening visit.
Number of Participants Who Achieved SLE Responder Index (SRI-4) Response (a Disease Activity Composite Index) Baseline: Core study Screening; LTE Day 1, Week 24, Week 48, Week 72 and Week 96 SRI-4 response was defined as greater than or equal to 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline Physician's Global Assessment of Disease Activity (PGA). SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Number of Participants Who Achieved BILAG-based Combined Lupus Assessment (BICLA) Response (a Disease Activity Composite Index) Baseline: Core study Screening; LTE Day 1, Week 24, Week 48, Week 72 and Week 96 The BICLA response was defined as BILAG-2004 improvement (all screening visit BILAG A improving to B/C/D, all screening visit BILAG B to C/D, and less than or equal to (\<=1) new BILAG B and no new BILAG A); no deterioration in SLEDAI total score; PGA increase by less than (\<) 0 percentage (%) (defined as less then (\<)0.3 point increase for the statistical analyses) and no non-permitted medication/treatment. Baseline was defined as core study screening visit.
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score Baseline (Core Study Day 1); LTE Day 1, Week 24, Week 48, Week 72 and Week 96 The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) is based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100=highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100=highest level of physical functioning).
Percent Change From Baseline in Prednisone-equivalent Corticosteroid Dose Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96 Number of Participants With Patient Global Impression of Change (PGIC) Baseline (Core Study Day 1); LTE Day 1, Week 24, Week 48, Week 72 and Week 96 The PGIC is self-rated scale that asks the participant to describe the change in activity limitations, symptoms, emotions, and overall Quality of life (QoL) related to the participant'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). Number of participants in the PGIC categories of very much improved (1) and much improved (2) are reported.
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score LTE Day 1, Week 24, Week 48, Week 72 and Week 98 The C-SSRS assesses the suicidal behavior and suicidal ideation in participants. Occurrence of suicidal behavior after study entry is defined as having answered "yes" to a least 1 of the 4 suicidal behavior subcategories (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). Occurrence of suicidal ideation is defined as having answered "yes" to at least 1 of the suicidal ideation sub-categories (1) wish to be dead, (2) nonspecific active suicidal thoughts, (3) active suicidal ideation with any methods (no plan) without intent to act, (4) active suicidal ideation with some intent to act (without specific plan), and (5) active suicidal ideation with specific plan and intent).
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Baseline (Core Study Day 1); LTE Day 1, Week 24, Week 48, Week 72, and Week 96 The LupusQoL was a lupus-specific health related QoL (HRQoL) questionnaire consisting of 34 items grouped in 8 domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4 = never, 3 = occasionally, 2 = a good bit of the time, 1 = most of the time, and 0 = all of the time. Summary scores can be calculated for all 8 domains. A LupusQoL score for each domain was reported on a 0 to 100 scale, with greater values indicating better HRQoL. Baseline was defined as Day 1 of core study.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score Baseline: Day 1 (Core study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96 The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.
Change From Baseline in EuroQoL 5 Dimension Instrument (EQ-5D) Score Baseline: Day 1 (Core Study), LTE Day 1, Week 24, Week 48, Week 72 and Week 96 EQ-5D questionnaire comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels; 1=no problem, 2=moderate problems, 3=extreme problems. This part, called the EQ-5D descriptive system, provides a 5-dimensional description of health status. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state. Baseline was defined as Day 1 of Core study.
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores Baseline: Day 1 (Core Study), LTE Day 1, Week 24, Week 48, Week 72 and Week 96 EQ-5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeters (mm) (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. Baseline defined as Day 1 of core study.
Number of Participants With at Least One Adverse Event Baseline (Day 1 of Core study) up to maximum duration of 167.7 weeks An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. Treatment-Emergent adverse events (TEAEs) are defined as events with an onset date on or after the date of first dose of study treatment in the core study and ongoing at LTE study entry, or occurring during LTE study.
Trial Locations
- Locations (84)
Clinica de Enfermedades Cronicas y de Procedimientos Especiales, S.C.
🇲🇽Morelia, Michoacán, Mexico
Mary Mediatrix Medical Center
🇵ðŸ‡Batangas, Philippines
Icle S.C.
🇲🇽Guadalajara, Jalisco, Mexico
Centro de Pesquisas em Diabetes Ltda.
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Naidoo, A
🇿🇦Durban, KwaZulu-Natal, South Africa
East Bay Rheumatology Medical Group, Inc.
🇺🇸San Leandro, California, United States
Clinical Research of West Florida - Corporate
🇺🇸Clearwater, Florida, United States
Rutgers New Jersey Medical School
🇺🇸Newark, New Jersey, United States
MetroHealth System
🇺🇸Cleveland, Ohio, United States
SBHI of Yaroslavl Region "Clinical Hospital # 8"
🇷🇺Yaroslavl, Russian Federation
Hospital for Special Surgery
🇺🇸New York, New York, United States
Pinnacle Research Group LLC
🇺🇸Anniston, Alabama, United States
Medical Center "Teodora", EOOD
🇧🇬Ruse, Bulgaria
Southern California Permenent Medical Group
🇺🇸Fontana, California, United States
AA MRC LLC Ahmed Arif Medical Research Center
🇺🇸Grand Blanc, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
The Feinstein Institute for Medical Research
🇺🇸Manhasset, New York, United States
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Quantum Research Santiago
🇨🇱Puerto Varas, Chile
Morales Vargas Centro de Investigacion, S.C.
🇲🇽Leon, Guanajuato, Mexico
Centro Medico Prosalud
🇨🇱Santiago, Chile
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Invest Clinicas Sac Inst de Ginecologia y Reproduccion
🇵🇪Lima, Peru
SBIH of Republic Kareliya "Republican Hospital n.a. V.A. Baranov"
🇷🇺Petrozavodsk, Russian Federation
Centro de Estudios Reumatologicos
🇨🇱Santiago, Chile
FSBEI HE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF
🇷🇺Moscow, Russian Federation
Corporacion de Beneficencia Osorno
🇨🇱Osorno, Chile
Biomedica
🇨🇱Santiago, Chile
DJL Clinical Research, PLLC
🇺🇸Charlotte, North Carolina, United States
Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
🇧🇬Stara Zagora, Bulgaria
Investigaciones Clinicas Tucuman
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
Cordis S.A.
🇦🇷Salta, Argentina
Clinical Research Center of Reading LLC
🇺🇸Wyomissing, Pennsylvania, United States
Instituto CAICI
🇦🇷Rosario, Santa Fe, Argentina
Hospital Privado Centro Medico de Cordoba
🇦🇷Cordoba, Argentina
Centro Integral de Reumatologia
🇦🇷San Miguel de Tucumán, Tucuman, Argentina
Revmatologicky Ustav
🇨🇿Praha 2, Czechia
CINVEC - Centro de Investigacion Clinica V Region
🇨🇱Viña del Mar, Chile
MHAT "Eurohospital" - Plovdiv, OOD
🇧🇬Plovdiv, Bulgaria
Queen's Hospital
🇬🇧Romford, Essex, United Kingdom
DCC "Sveta Anna", EOOD
🇧🇬Sofia, Bulgaria
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
🇩🇪Mainz, Rheinland Pfalz, Germany
Centro Multidisciplinario para el desarrollo Especializado de la Investigacion Clinica en Yucatan
🇲🇽Merida, Yucatán, Mexico
Hospital Universitario de Saltillo "Dr. Gonzalo Valdés Valdés"
🇲🇽Saltillo, Coahuila, Mexico
Revmatologicka ambulance
🇨🇿Uherske Hradiste, Czechia
University of Alabama at Birmingham - (UAB)
🇺🇸Birmingham, Alabama, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
OMRF
🇺🇸Oklahoma City, Oklahoma, United States
MHAT-Targovishte, AD
🇧🇬Targovishte, Bulgaria
Clayton Medical Associates, P.C.
🇺🇸Saint Louis, Missouri, United States
Arthritis & Rheumatology Center of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
🇩🇪Berlin, Germany
Wallace Rheumatic Study Center
🇺🇸Beverly Hills, California, United States
Little River Arthritis & Osteoporosis Clinic
🇺🇸Waco, Texas, United States
Organizacion Medica de Investigacion (OMI)
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Atencion Integral en Reumatologia (AIR)
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Centro Polivalente de Asistencia e Inv. Clinica CER
🇦🇷San Juan, Argentina
Centro Medico Privado de Reumatologia
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
APRILLUS
🇦🇷Ciudad Autonoma Buenos aires, Argentina
UMHAT "Sv. Ivan Rilski", EAD
🇧🇬Sofia, Bulgaria
MHAT - Ruse, AD
🇧🇬Ruse, Bulgaria
Seoul National University Hospital
🇰🇷Seoul, Gyeonggi-do, Korea, Republic of
Unidad de Investigacion en Enfermedades Cronico Degenerativas SC
🇲🇽Guadalajara, Jalisco, Mexico
Hogar ClÃnica San Juan de Dios - Arequipa
🇵🇪Arequipa, Peru
Investigacion y Biomedicina de Chihuahua, S.C.
🇲🇽Chihuahua, Mexico
Clinica Medica Cayetano Heredia
🇵🇪Lima, Peru
Angeles University Foundation Medical Center
🇵ðŸ‡Angeles City, Pampanga, Philippines
Davao Doctors Hospital
🇵ðŸ‡Davao, Philippines
Iloilo Doctors Hospital
🇵ðŸ‡Iloilo, Philippines
Winelands Medical Research Centre
🇿🇦Stellenbosch, Western Cape, South Africa
SIH "Saratov City Clinical Hospital # 12"
🇷🇺Saratov, Russian Federation
Hospital Clinico Universitario de Valladolid
🇪🇸Valladolid, Spain
SBIH of Vladimir region "Regional Clinical Hospital"
🇷🇺Vladimir, Russian Federation
SPb SBIH "Clinical Rheumatological Hospital # 25"
🇷🇺Saint-Petersburg, Russian Federation
University College London Hospitals
🇬🇧London, Greater London, United Kingdom
Szpital Uniwersytecki nr 2 im.dr J. Biziela
🇵🇱Bydgoszcz, Poland
Accelerium S. de R.L. de C.V.
🇲🇽Monterrey, Nuevo León, Mexico
Clinstile, S.A. de C.V.
🇲🇽Mexico, Distrito Federal, Mexico
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
Austin Regional Clinic, P.A.
🇺🇸Austin, Texas, United States
McIlwain Medical Group, PA
🇺🇸Tampa, Florida, United States
Clinical Research of West Florida, Inc.
🇺🇸Tampa, Florida, United States
Guy's Hospital
🇬🇧London, Greater London, United Kingdom