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A Phase II Study of M2951 in Systemic Lupus Erythematosus (SLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02975336
Recruitment Status : Active, not recruiting
First Posted : November 29, 2016
Last Update Posted : May 20, 2020
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information
First Submitted Date  ICMJE November 23, 2016
First Posted Date  ICMJE November 29, 2016
Last Update Posted Date May 20, 2020
Actual Study Start Date  ICMJE January 4, 2017
Actual Primary Completion Date November 27, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 23, 2016)
  • Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): All Subjects [ Time Frame: Week 52 ]
  • Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6): High Disease Activity (HDA) Subgroup Subjects [ Time Frame: Week 52 ]
  • Occurrences of Subjects With Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs) [ Time Frame: Baseline up to Week 56 ]
  • Occurrences of Treatment-emergent Adverse Events (TEAEs) According to Severity [ Time Frame: Baseline up to Week 56 ]
  • Number of Subjects With Clinically Significant Vital signs, Electrocardiogram (ECG) and Laboratory Abnormalities [ Time Frame: Baseline up to Week 56 ]
  • Serum Total Immunoglobulin (Ig) levels [ Time Frame: up to Week 56 ]
  • Total B Cell Counts [ Time Frame: up to Week 56 ]
  • Change From Baseline to Week 56 in Serum total Immunoglobulin (Ig) levels [ Time Frame: Baseline, up to Week 56 ]
  • Change From Baseline to Week 56 in Total B Cell Counts [ Time Frame: Baseline, up to Week 56 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
  • Time to First Severe Flare [ Time Frame: Baseline up to Week 52 ]
  • Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): Serologically Active Subgroup [ Time Frame: Week 52 ]
  • Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6): Serologically Active Subgroup [ Time Frame: Week 52 ]
  • Time to First Flare [ Time Frame: Baseline up to Week 52 ]
  • Flare-free Status [ Time Frame: Week 52 ]
  • Annualized Flare Rate [ Time Frame: Baseline up to Week 52 ]
  • Low Disease Activity Status, Defined by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score of <= 2 at Week 52 [ Time Frame: Week 52 ]
  • Low Disease Activity Status, Defined by Clinical SLEDAI-2K Score of <= 2 at Week 52 [ Time Frame: Week 52 ]
  • Change From Baseline in SLEDAI-2K Score by Visit [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score by Visit [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Number of Subjects With Response Based on BILAG-Based Composite Lupus Assessment (BICLA) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Change From Baseline in BILAG-2004 by Visit [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Change From Baseline in Physician's Global Assessment (PGA) by Visit [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Change From Baseline in Study 36-Item Short Form Health Survey version 2 (SF-36v2) Physical Component Score and Mental Component Scores by Visit [ Time Frame: Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Change From Baseline in EuroQoL 5 Dimension 5 Levels (EQ-5D-5L) Scale Score by Visit [ Time Frame: Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Change From Baseline in Lupus Quality of Life (LupusQoL) Scale Score by Visit [ Time Frame: Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Patient Global Impression of Change (PGIC) Scale Score by Visit [ Time Frame: Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit [ Time Frame: Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Number of Subjects With Change From Baseline in Prednisone-equivalent Corticosteroid (CS) dose by >=25% to a dose of <=7.5 mg/day, with no BILAG A or 2B Flare in Disease Activity [ Time Frame: up to Week 52 ]
  • Change From Baseline to Week 52 in Prednisone-equivalent CS daily dose [ Time Frame: Baseline, up to Week 52 ]
  • Change From Baseline to Week 52 in Prednisone-equivalent CS Daily Dose of 0 to < 25%, 25% to 50%, > 50%, or an increase [ Time Frame: Baseline, up to Week 52 ]
  • Cumulative Prednisone-equivalent CS dose [ Time Frame: Baseline up to Week 52 ]
  • Clinically Meaningful Change in CS Dose From Baseline [ Time Frame: up to Week 52 ]
  • Number of Subjects with a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 milligrams prednisone equivalent per day or less With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): all subject [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose less than or equal to (<=) Day 1 dose With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): all subject [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose to 7.5 milligrams prednisone equivalent per day or less With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6): HDA subgroup [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose less than or equal to (<=) Day 1 dose Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6): HDA subgroup [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose to 7.5 milligrams prednisone equivalent per day or less With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): Serologically Active Subgroup [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose less than or equal to (<=) Day 1 dose With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): Serologically Active Subgroup [ Time Frame: Week 52 ]
  • Lupus Low Disease Activity State [ Time Frame: Week 52 ]
    Lupus low disease activity state will be measured as: SLEDAI-2K <= 4; No activity in any major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever); No new features of disease activity compared with the previous assessment; Prednisone-equivalent <= 7.5 milligram per day; Unchanged background immunosuppressive therapy.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 23, 2016)
  • Time to First Severe Flare [ Time Frame: Baseline up to Week 52 ]
  • Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): Serologically Active Subgroup [ Time Frame: Week 52 ]
  • Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6): Serologically Active Subgroup [ Time Frame: Week 52 ]
  • Time to First Flare [ Time Frame: Baseline up to Week 52 ]
  • Flare-free Status [ Time Frame: Week 52 ]
  • Annualized Flare Rate [ Time Frame: Baseline up to Week 52 ]
  • Change From Baseline in Low Disease Activity, Defined by SLEDAI-2K Score of <= 2 at Week 52 [ Time Frame: Baseline, Week 52 ]
  • Change From Baseline in Low Disease Activity, Defined by Clinical SLEDAI-2K Score of <= 2 at Week 52 [ Time Frame: Baseline, Week 52 ]
  • Change From Baseline in SLEDAI-2K Score at Each Visit [ Time Frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Each Visit [ Time Frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Number of Subjects With Response Based on BILAG-Based Composite Lupus Assessment (BICLA) [ Time Frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Change From Baseline in BILAG-2004 at Each Visit [ Time Frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Change From Baseline in Physician's Global Assessment (PGA) at Each Visit [ Time Frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  • Change From Baseline in Study 36-Item Short Form Health Survey version 2 (SF-36v2) Physical Component Score and Mental Component Scores at Each Visit [ Time Frame: Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Change From Baseline in EuroQoL 5 Dimension 5 Levels (EQ-5D-5L) Scale Score at Each Visit [ Time Frame: Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Change From Baseline in Lupus Quality of Life (LupusQoL) Scale Score at Each Visit [ Time Frame: Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Patient Global Impression of Change (PGIC) Scale Score [ Time Frame: Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at Each Visit [ Time Frame: Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52 ]
  • Number of Subjects With Change From Baseline in Prednisone-equivalent Corticosteroid (CS) dose by >=25% to a dose of <=7.5 mg/day, with no BILAG A or 2B Flare in Disease Activity [ Time Frame: up to Week 52 ]
  • Change From Baseline to Week 52 in Prednisone-equivalent CS daily dose [ Time Frame: Baseline, up to Week 52 ]
  • Change From Baseline to Week 52 in Prednisone-equivalent CS Daily Dose of 0 to < 25%, 25% to 50%, > 50%, or an increase [ Time Frame: Baseline, up to Week 52 ]
  • Cumulative Prednisone-equivalent CS dose [ Time Frame: Baseline up to Week 52 ]
  • Clinically Meaningful Change in CS Dose From Baseline [ Time Frame: up to Week 52 ]
  • Number of Subjects with a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 milligrams prednisone equivalent per day or less With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): all subject [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose less than or equal to (<=) Day 1 dose With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): all subject [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose to 7.5 milligrams prednisone equivalent per day or less With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6): HDA subgroup [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose less than or equal to (<=) Day 1 dose Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6): HDA subgroup [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose to 7.5 milligrams prednisone equivalent per day or less With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): Serologically Active Subgroup [ Time Frame: Week 52 ]
  • Number of Subjects with a Sustained Reduction of OCS Dose less than or equal to (<=) Day 1 dose With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): Serologically Active Subgroup [ Time Frame: Week 52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Study of M2951 in Systemic Lupus Erythematosus (SLE)
Official Title  ICMJE A Phase II, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study To Evaluate the Safety and Efficacy of M2951 in Subjects With Systemic Lupus Erythematosus (SLE)
Brief Summary M2951 is an investigational drug under evaluation for treatment of autoimmune and inflammatory disorders. The purpose of the study is to assess the Safety and Efficacy of M2951 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 Systemic Lupus Erythematosus
Intervention  ICMJE
  • Drug: Placebo
    Placebo matched to M2951 will be administered for 52 weeks in double-blind treatment period.
  • Drug: M2951
    M2951 low dose will be administered for 52 weeks in double-blind treatment period.
    Other Name: Evobrutinib
  • Drug: M2951
    M2951 mid dose will be administered for 52 weeks in double-blind treatment period.
    Other Name: Evobrutinib
  • Drug: M2951
    M2951 high dose will be administered for 52 weeks.
    Other Name: Evobrutinib
  • Drug: M2951
    M2951 will be administered for 104 weeks in open-lable extension period at a dose of 50 milligrams twice a day.
    Other Name: Evobrutinib
Study Arms  ICMJE
  • Placebo Comparator: Placebo: Double-Blind Treatment Period
    Intervention: Drug: Placebo
  • Experimental: M2951: Double-Blind Treatment Period
    Intervention: Drug: M2951
  • Experimental: M2951 Mid Dose: Double-Blind Treatment Period
    Intervention: Drug: M2951
  • Experimental: M2951 High dose: Double-Blind Treatment Period
    Intervention: Drug: M2951
  • Experimental: M2951: Open-Label Extension Period
    Intervention: Drug: M2951
Publications * Not Provided

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 16, 2019)
480
Original Estimated Enrollment  ICMJE
 (submitted: November 23, 2016)
432
Estimated Study Completion Date  ICMJE August 1, 2022
Actual Primary Completion Date November 27, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Eligible male and female subjects, aged 18 to 75 years
  • Must have diagnosis of SLE with either the Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE, or at least four of the 11 American College of Rheumatology (ACR) classification criteria for SLE, of at least six months duration prior to Screening
  • SLEDAI-2K total score greater than or equal to (>=) 6 (including clinical SLEDAI greater than or equal to (>=) 4) at Screening Visit
  • And be positive for anti-double-stranded Deoxyribonucleic Acid (DNA) and/or anti-nuclear antibody (ANA greater than or equal to (>=) 1:80) and/or anti-Smith (anti-Sm) antibody at the time of Screening
  • Other protocol defined inclusion criteria could apply.

Exclusion Criteria:

  • Subjects are not eligible for this study if they have active, clinically significant interstitial lung disease or pulmonary arterial hypertension
  • Proteinuria (urine protein to creatinine ratio [UPCR] > 4 mg/mg)
  • Acutely worsened renal function
  • Central nervous system SLE
  • Or within two weeks prior to Screening or during Screening: use of oral corticosteroids greater than (>) 30 mg daily prednisone equivalent
  • Use of injectable corticosteroids, or change in dose of corticosteroids.
  • Other protocol defined exclusion criteria could apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (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,   Bulgaria,   Chile,   Colombia,   Germany,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mauritius,   Mexico,   Peru,   Philippines,   Poland,   Romania,   Russian Federation,   South Africa,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02975336
Other Study ID Numbers  ICMJE MS200527-0018
2016-002950-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Study Sponsor  ICMJE EMD Serono Research & Development Institute, Inc.
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date May 2020

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