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Efficacy and Safety of Atacicept in Systemic Lupus Erythematosus (ADDRESS II)

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ClinicalTrials.gov Identifier: NCT01972568
Recruitment Status : Completed
First Posted : October 30, 2013
Results First Posted : October 26, 2017
Last Update Posted : January 2, 2018
Sponsor:
Information provided by (Responsible Party):
EMD Serono

Tracking Information
First Submitted Date  ICMJE October 24, 2013
First Posted Date  ICMJE October 30, 2013
Results First Submitted Date  ICMJE September 29, 2017
Results First Posted Date  ICMJE October 26, 2017
Last Update Posted Date January 2, 2018
Actual Study Start Date  ICMJE December 2013
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2017)
  • Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline [ Time Frame: Week 24 ]
    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.
  • Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Day 1 as Baseline [ Time Frame: Week 24 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2013)
Percentage of subjects with SLE responder index (SRI) response at Week 24 compared to screening [ Time Frame: Screening and Week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2017)
  • 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 [ Time Frame: Week 24 ]
    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.
  • Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 [ Time Frame: 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.
  • Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24 [ Time Frame: Screening and Week 24 ]
    Change From screening visit to Week 24 of prednisolone-equivalent CS daily dose was presented.
  • Time From Randomization to First SRI Response During Treatment Period [ Time Frame: Baseline up to 24 Weeks ]
    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.
  • Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24 [ Time Frame: 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.
  • Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: Baseline up to 24 weeks after last dose of study drug (assessed up to maximum of 48 weeks) ]
    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.
  • Change From Week 0 (Day 1) in SF-36 Components at Week 24 [ Time Frame: Week 0 (Day 1) and 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2013)
  • Percentage of subjects at Week 24 whose prednisone-equivalent corticosteroid dose has reduced from Screening by >= 25 percent and to a dose of =< 7.5 milligram per day (mg/day), and have no BILAG A or 2B flare in disease activity during Weeks 16 to 24 [ Time Frame: Screening and Week 24 ]
  • Percentage of subjects in the patient global impression of change (PGIC) categories at Week 24 [ Time Frame: Week 24 ]
  • Change from screening visit to Week 24 in prednisone-equivalent corticosteroid (CS) daily dose [ Time Frame: Screening and Week 24 ]
  • Time to first SRI response during the treatment period [ Time Frame: 24 Weeks ]
  • Percentage of subjects responding to treatment according to British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) [ Time Frame: Week 24 ]
  • Change from Day 1 in medical outcomes study 36-item short form health survey (SF-36)-physical component summary (PCS) and mental component summary (MCS) [ Time Frame: Week 24 ]
  • Number of subjects with adverse events (AEs) [ Time Frame: Screening up to 48 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Atacicept in Systemic Lupus Erythematosus
Official Title  ICMJE 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)
Brief 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Lupus Erythematosus, Systemic
Intervention  ICMJE
  • Drug: Atacicept 75 milligram (mg)
    Atacicept 75 mg will be administered as subcutaneous injection once weekly for 24 weeks.
  • Drug: Atacicept 150 mg
    Atacicept 150 mg will be administered as subcutaneous injection once weekly for 24 weeks.
  • Drug: Placebo
    Placebo matched to atacicept will be administered as subcutaneous injection once weekly for 24 weeks.
Study Arms  ICMJE
  • Experimental: Atacicept 75 mg
    Intervention: Drug: Atacicept 75 milligram (mg)
  • Experimental: Atacicept 150 mg
    Intervention: Drug: Atacicept 150 mg
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 9, 2015)
306
Original Estimated Enrollment  ICMJE
 (submitted: October 24, 2013)
279
Actual Study Completion Date  ICMJE September 2016
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Bulgaria,   Chile,   Czechia,   Germany,   Italy,   Japan,   Korea, Republic of,   Mexico,   Peru,   Philippines,   Poland,   Russian Federation,   South Africa,   Spain,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Ukraine
 
Administrative Information
NCT Number  ICMJE NCT01972568
Other Study ID Numbers  ICMJE 700461-023
2013-002773-21 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party EMD Serono
Study Sponsor  ICMJE EMD Serono
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Responsible EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP