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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02975336
• Date of registration: 23/11/2016
• Prospective Registration: Yes
• Primary sponsor: EMD Serono Research & Development Institute, Inc.
• Public title: A Phase II Study of M2951 in Systemic Lupus Erythematosus (SLE)
• Scientific title: 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)
• Date of first enrolment: January 4, 2017
• Target sample size: 480
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02975336
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Argentina, Bulgaria, Chile, Colombia, Germany, Italy, Japan, Korea, Republic of, Malaysia, Mauritius, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, South Africa, Taiwan, United States

Contacts

• Name: Medical Responsible
• Affiliation: EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: M2951

Drug: Placebo

Primary Outcome(s)

Number of Subjects With Clinically Significant Vital signs, Electrocardiogram (ECG) and Laboratory Abnormalities [Time Frame: Baseline up to Week 56]

Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): All 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]

Change From Baseline to Week 56 in Total B Cell Counts [Time Frame: Baseline, 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]

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]

Serum Total Immunoglobulin (Ig) levels [Time Frame: up to Week 56]

Occurrences of Treatment-emergent Adverse Events (TEAEs) According to Severity [Time Frame: Baseline up to Week 56]

Secondary Outcome(s)

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 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]

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]

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]

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]

Clinically Meaningful Change in CS Dose From Baseline [Time Frame: up to Week 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]

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]

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]

Cumulative Prednisone-equivalent CS dose [Time Frame: Baseline up to 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]

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]

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 to Week 52 in Prednisone-equivalent CS daily dose [Time Frame: Baseline, up to 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 Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): Serologically Active Subgroup [Time Frame: Week 52]

Annualized Flare Rate [Time Frame: Baseline up to Week 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]

Flare-free Status [Time Frame: Week 52]

Low Disease Activity Status, Defined by Clinical SLEDAI-2K Score of <= 2 at Week 52 [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 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 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]

Time to First Flare [Time Frame: Baseline up to Week 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]

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]

Lupus Low Disease Activity State [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]

Patient Global Impression of Change (PGIC) Scale Score by Visit [Time Frame: Week 4, 8, 12, 16, 24, 32, 40, and 52]

Time to First Severe Flare [Time Frame: Baseline up to Week 52]

Secondary ID(s)

MS200527-0018

2016-002950-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck KGaA, Darmstadt, Germany