MSC2364447C Phase 1b in Systemic Lupus Erythematosus

A Phase Ib Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Biological Effect of MSC2364447C in Systemic Lupus Erythematosus

The primary purpose of this Phase 1b double-blind, randomized, placebo-controlled trial is to evaluate the safety, tolerability, pharmacokinetic (PK), and biological effect of MSC2364447C administered for 4 weeks in systemic lupus erythematosus subjects (SLE).

Study Overview

• Status: Completed
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Drug: MSC2364447C; Drug: MSC2364447C; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1431
    • Research Site
  • Sofia, Bulgaria, 1336
    • Research Site
  • Sofia, Bulgaria, 1612
    • Research Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Research Site
  • California
    • El Cajon, California, United States, 92020-4124
      • Research Site
    • Lakewood, California, United States, 90712
      • Research Site
    • Los Angeles, California, United States, 90048
      • Research Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Research Site
    • DeBary, Florida, United States, 32713
      • Research Site
    • Orlando, Florida, United States, 32806
      • Research Site
  • Michigan
    • Grand Blanc, Michigan, United States, 48439
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Research Site
  • Texas
    • Austin, Texas, United States, 78745
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female of 18 to 65 years of age
• Diagnosis of systemic lupus erythematosus (SLE) (at least 4 of the 11 American College of Rheumatology [ACR] classification criteria for SLE) of at least 6 months duration at the Screening visit
• Positive test results for anti-nuclear antibody (ANA) (human epithelial cell-2 ANA greater than or equal to [>=] 1:80) and/or anti-dsDNA antibody (>= 30 international units per milliliter [IU/mL]) at the Screening visit
• At least 1 SLE disease manifestation (assessed by Systemic Lupus Erythematosus Disease Activity Index-2000 [SLEDAI-2K]) other than positive antidsDNA and no central nervous system (CNS) SLE (psychosis, organic brain syndrome, cranial nerve disorder, lupus headache, or new-onset cerebrovascular accident)

• History of vaccinations as follows or vaccination against these pathogens during Screening:

  1. Vaccination against Streptococcus pneumoniae with pneumococcal polysaccharide vaccine 23 or pneumococcal 13-valent conjugate vaccine as per local guidelines, and
  2. Vaccination against influenza virus (as per local seasonal recommendations). Subjects receiving 1 or more of these vaccinations during screening must have at least 2 weeks between the vaccination(s) and the date of randomization at Day 1.
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Active clinically significant CNS SLE
• Initiation or change in dose of anti-malarial treatment after the screening visit
• Within 2 weeks prior to Screening or during Screening: use of oral corticosteroids greater than (>) 40 mg daily prednisone equivalent, use of any injectable corticosteroids, or change in dose of corticosteroids
• Within 2 weeks prior to Screening, initiation or change in dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, or nonsteroidal anti-inflammatory drugs (NSAIDs).
• Within 2 months prior to Screening or during Screening: initiation of or change in dose of methotrexate, mycophenolate (mofetil or sodium), or azathioprine
• Within 2 months prior to Screening or during Screening, use of cyclosporine, tacrolimus, leflunomide, abatacept, anti-tumor necrosis factor alpha agents, intravenous immunoglobulin, plasmapheresis, or other disease-modifying, immunosuppressive, or immunomodulatory therapies not otherwise specified in protocol
• Within 6 months prior to Screening or during Screening: use of cyclophosphamide or chlorambucil
• Within 12 months prior to screening or during screening: use of rituximab, belimumab, or any other B cell-depleting or modulating therapies
• Within 1 month prior to Screening or during Screening, vaccination with live or live-attenuated virus vaccine.
• Active clinically significant viral, bacterial or fungal infection, or any serious episode of infection requiring hospitalization within the last 6 months - Estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation of less than (<) 60 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2), or recent decline in kidney function, or proteinuria >= 3 gram per day (g/day) (spot urine protein/creatinine ratio >= 3 mg/mg)
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Subjects will be administered with placebo matching to MSC2364447C orally once daily for 4 weeks.
Experimental: MSC2364447C 25 mg	Drug: MSC2364447C; Subjects will be administered with MSC2364447C 25 milligrams orally once daily for 4 weeks.; Other Names: M2951, Evobrutinib; Drug: MSC2364447C; Subjects will be administered with MSC2364447C 75 milligrams orally once daily for 4 weeks.; Other Names: M2951, Evobrutinib
Experimental: MSC2364447C 75 mg	Drug: MSC2364447C; Subjects will be administered with MSC2364447C 25 milligrams orally once daily for 4 weeks.; Other Names: M2951, Evobrutinib; Drug: MSC2364447C; Subjects will be administered with MSC2364447C 75 milligrams orally once daily for 4 weeks.; Other Names: M2951, Evobrutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with treatment emergent adverse events (TEAEs)	TEAEs will be defined as the adverse events (AEs) that occur between first dose of study drug administration up to 4 weeks after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.	From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
Number of subjects with TEAEs according to severity	The severity of TEAEs will be graded using National cancer institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v 4.03) definitions of Grade 1 through Grade 5 following his/her best medical judgment. The severity of the AEs will be classified as follows: Grade 1 or mild, Grade 2 or moderate, Grade 3 or severe, Grade 4 or life-threatening and Grade 5 or death.	From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
Number of subjects with clinically significant laboratory abnormalities	Clinical laboratory parameters being monitored for safety will be summarized using descriptive statistics, by postdose shifts relative to Baseline for relevant parameters using relevant cut-offs. Clinical significance will be determined by investigator.	screening up to Day 56
Number of subjects with clinically significant abnormal vital signs: blood pressure, pulse rate, respiratory rate	Observed values and changes from Baseline in vital signs will be summarized for each treatment group using descriptive statistics. Clinically noteworthy changes in vital signs will be listed and summarized as appropriate. A semi-automated blood pressure and pulse rate recording device with an appropriate cuff size will be utilized. Blood pressure and pulse rate will be measured after 10 minutes' rest in the semi-supine position with the subject's arm unconstrained by clothing or other material. The blood pressure should be assessed on the same arm for each subject throughout the trial. Clinical significance will be determined by investigator.	screening up to Day 56
Number of subjects with clinically significant abnormal electrocardiograms (ECGs)	Observed values and changes from Baseline in ECG will be summarized for each treatment group using descriptive statistics. Clinically noteworthy changes in ECG will be listed and summarized as appropriate. Clinical significance will be determined by investigator.	screening up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration-time curve from time zero to 6 hours after administration (AUC0-6)		Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Maximum observed plasma concentration (Cmax)		Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Time to reach maximum plasma concentration (tmax)		Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Concentration observed immediately before next dosing (Cpre) (Day 28)		Predose (within 30 minutes prior to dosing) on Day 28
Dose-normalized AUC0-6h (AUC0-6h/dose)		Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Dose-normalized Cmax (Cmax/dose)		Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Accumulation ratio for AUC0-6 (Racc(AUC0-6))	Accumulation ratio for AUC will be calculated as AUC0-6, Day28 divided by AUC0-6, Day1	Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Accumulation ratio for Cmax (Racc(Cmax))	Accumulation ratio for Cmax, calculated as Cmax, Day28 divided by Cmax, Day1	Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2015
• Primary Completion (Actual): October 4, 2016
• Study Completion (Actual): October 4, 2016

Study Registration Dates

• First Submitted: August 28, 2015
• First Submitted That Met QC Criteria: August 28, 2015
• First Posted (Estimate): September 1, 2015

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: October 6, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Lupus; Phase 1; Systemic Lupus Erythematosus; BTK inhibitor; M2951; MSC2364447C
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: EMR200527-002; 2015-001891-23 (EudraCT Number)