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MSC2364447C Phase 1b in Systemic Lupus Erythematosus

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ClinicalTrials.gov Identifier: NCT02537028
Recruitment Status : Completed
First Posted : September 1, 2015
Last Update Posted : October 9, 2017
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Lupus Erythematosus, Systemic Drug: MSC2364447C Drug: Placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase Ib Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Biological Effect of MSC2364447C in Systemic Lupus Erythematosus
Actual Study Start Date : November 30, 2015
Actual Primary Completion Date : October 4, 2016
Actual Study Completion Date : October 4, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Arm Intervention/treatment
Experimental: MSC2364447C 25 mg Drug: MSC2364447C
Subjects will be administered with MSC2364447C 25 milligrams orally once daily for 4 weeks.
Other Name: M2951, Evobrutinib

Experimental: MSC2364447C 75 mg Drug: MSC2364447C
Subjects will be administered with MSC2364447C 75 milligrams orally once daily for 4 weeks.
Other Name: M2951, Evobrutinib

Placebo Comparator: Placebo Drug: Placebo
Subjects will be administered with placebo matching to MSC2364447C orally once daily for 4 weeks.




Primary Outcome Measures :
  1. Number of subjects with treatment emergent adverse events (TEAEs) [ Time Frame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration ]
    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.

  2. Number of subjects with TEAEs according to severity [ Time Frame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration ]
    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.

  3. Number of subjects with clinically significant laboratory abnormalities [ Time Frame: screening up to Day 56 ]
    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.

  4. Number of subjects with clinically significant abnormal vital signs: blood pressure, pulse rate, respiratory rate [ Time Frame: screening up to Day 56 ]
    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.

  5. Number of subjects with clinically significant abnormal electrocardiograms (ECGs) [ Time Frame: screening up to Day 28 ]
    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.


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

  8. Accumulation ratio for Cmax (Racc(Cmax)) [ Time Frame: 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, calculated as Cmax, Day28 divided by Cmax, Day1



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02537028


Locations
United States, Alabama
Research site
Anniston, Alabama, United States, 36207
United States, California
Research site
El Cajon, California, United States, 92020-4124
Research site
Lakewood, California, United States, 90712
Research site
Los Angeles, California, United States, 90048
United States, Florida
Research site
Clearwater, Florida, United States, 33765
Research site
DeBary, Florida, United States, 32713
Research site
Orlando, Florida, United States, 32806
United States, Michigan
Research site
Grand Blanc, Michigan, United States, 48439
United States, Missouri
Research site
Saint Louis, Missouri, United States, 63117
United States, Texas
Research site
Austin, Texas, United States, 78745
Bulgaria
Research site
Sofia, Bulgaria, 1336
Research site
Sofia, Bulgaria, 1431
Research site
Sofia, Bulgaria, 1612
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
Study Director: Medical Responsible EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany

Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT02537028     History of Changes
Other Study ID Numbers: EMR200527-002
2015-001891-23 ( EudraCT Number )
First Posted: September 1, 2015    Key Record Dates
Last Update Posted: October 9, 2017
Last Verified: October 2017

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
MSC2364447C
Phase 1
BTK inhibitor
Systemic Lupus Erythematosus
M2951
Lupus

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases