Safety and Efficacy Study of M2951 in Participants With Rheumatoid Arthritis

NCT02784106 | Completed Phase 2 Results DMC

• 2 other identifiers: MS200527-00812016-000064-42
• Study Type: interventional
• Target: 65
• Locations: 2 countries
• Sites: 2

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 efficacy of M2951 in participants with rheumatoid arthritis (RA) currently treated with stable dose of methotrexate (MTX).

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; M2951; Bruton's Tyrosine Kinase (BTK)

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Who Achieved American College of Rheumatology-20 (ACR20) Response

  ACR 20 response: greater than or equal to (\>=) 20 percent (%) improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with \>=20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Proportion of ACR20 responders = Number of participants with ACR20 response divided by total participants.

  Day 84

Secondary Outcomes (30)

• Mean Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Day 28

  Baseline, Day 28

• Proportion of Participants Achieving American College of Rheumatology-50 (ACR50) Response

  Day 28, Day 56 and Day 84

• Proportion of Participants Achieving American College of Rheumatology-70 (ACR70) Response

  Day 28, Day 56 and Day 84

• Mean Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Day 84

  Baseline, Day 84

• Mean Change From Baseline in Disease Activity Score Based on a 28 Joint Count High-Sensitivity C-Reactive Protein (DAS28-hsCRP) at Day 28 and 84

  Baseline, Day 28 and Day 84

Study Arms (4)

Placebo: Double-Blind Treatment Period

PLACEBO COMPARATOR

Drug: Placebo

M2951: Double-Blind Treatment Period

EXPERIMENTAL

Drug: M2951

Placebo/M2951: Open Label Extension Period

EXPERIMENTAL

Drug: M2951

M2951/M2951: Open Label Extension Period

EXPERIMENTAL

Drug: M2951

Interventions

Placebo DRUG

Participants received placebo matched to M2951 twice daily up to Day 84 during the double-blind treatment period.

Placebo: Double-Blind Treatment Period

M2951 DRUG

Participants received 50 milligrams (mg) M2951 orally twice daily up to Day 84 during the double-blind treatment period.

Also known as: Evobrutinib

M2951: Double-Blind Treatment Period

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women 18 to 75 years of age at the time of informed consent signature
• Confirmed diagnosis of RA according to 2010 American College of Rheumatology (ACR)/The European League Against Rheumatism (EULAR) RA classification criteria of at least 6 months duration
• Positive RF and/or anti-CCP (anti-cyclic citrullinated peptide)
• Persistently active disease defined as greater than equal to (\>=) 6 swollen joints (of 66 counted) and \>= 6 tender joints (of 68 counted)
• High-sensitivity C-reactive protein (hsCRP) \>= 3.6 milligram per liter (mg/L)
• Treatment for \>= 12 weeks with 10 to 25 mg/week MTX at a stable dose for at least 4 weeks prior to dosing with the investigational medicinal product (IMP) and maintained throughout the trial
• Women of childbearing potential must use acceptable methods of contraception for 4 weeks prior to randomization, throughout the trial, and for 90 days after the last dose of IMP. For the purposes of this trial
• Females who are postmenopausal (age-related amenorrhea \>= 12 consecutive months and increased follicle-stimulating hormone \[FSH\] greater than (\>) 40 milli international units per milliliter \[mIU/mL\]), or who have undergone hysterectomy or bilateral oophorectomy are exempt from pregnancy testing. If necessary to confirm postmenopausal status, an FSH will be drawn at Screening
• Acceptable contraception is defined as use of either 2 barrier methods (eg, female diaphragm and male condom), or 1 barrier method in conjunction with one of the following: spermicide, an intrauterine device, or hormonal contraceptives (implant or oral)
• Women of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at Day 1/randomization before dosing.

You may not qualify if:

• Use of oral corticosteroids \> 10 mg daily prednisone equivalent, use of injectable corticosteroids, or change in dose of corticosteroids within 2 weeks prior to Screening or during Screening
• Initiation or change in dose for nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to Screening
• Treatment with tofacitinib, other Bruton's Tyrosine Kinase (BTK) inhibitors, or a biologic disease-modifying antirheumatic drug (DMARD; eg, anti-tumor necrosis factor alpha \[anti-TNF-α\], tocilizumab \[anti-interleukin-6 receptor\], abatacept \[CTLA4-Fc\]), or other immunosuppressive drugs(sulfasalazine would be acceptable at a stable dose) other than methotrexate within 3 months prior to Screening or during Screening
• Treatment with anti-CD20 therapy (eg, rituximab) within 12 months prior to Screening or during Screening
• Immunologic disorder other than Rheumatoid Arthritis (RA), with the exception of secondary Sjogren's syndrome associated with RA, and well-controlled diabetes or thyroid disorder, or any other condition requiring oral, intravenous, intramuscular, or intra-articular corticosteroid therapy
• Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening
• History of or positive testing for human immunodeficiency virus (HIV), hepatitis C antibody and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg) (+) and/or hepatitis B core total, and/or IgM antibody (+) at Screening
• History of or current diagnosis of active tuberculosis (TB); undergoing treatment for latent TB infection (LTBI); untreated LTBI (as determined by documented results within 3 months of the Screening Visit of a positive TB skin test with purified protein derivative with induration \>= 5 millimeter (mm), a positive QuantiFERON-TB test or positive or borderline T-SPOT \[Elispot\] test); or positive QuantiFERON-TB test at Screening. Participants with documented completed appropriate LTBI treatment would not be excluded and are not required to be tested
• Participants with current household contacts with active TB will also be excluded
• Indeterminate QuantiFERON-TB or T-SPOT tests may be repeated once, and will be considered positive if retest results are positive or indeterminate
• History of cancer, except adequately treated basal cell or squamous cell carcinomas of the skin (no more than 3 lesions requiring treatment in lifetime) or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix, unless considered cured \> 5 years
• Clinically significant abnormality on electrocardiogram (ECG), or an active infective process or any other clinically significant abnormality on Screening chest X-ray (CXR) taken within 4 weeks of the first dose, per Investigator opinion. If a CXR has been taken within the previous 3 months and results are available and normal, the CXR does not need to be carried out
• B cell (CD19) count less than (\<) 50% of the lower limit of normal at Screening
• Significant cytopenia including absolute neutrophil count \< 1,500/ mm\^3, platelet count \< 100,000/mm\^3, or absolute lymphocyte count \< 1,000/mm\^3

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (2)

U.S. Medical Information

Billerica, Massachusetts, United States

Location

Merck KGaA Communication Center

Darmstadt, Germany

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

evobrutinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: May 26, 2016
• Study Start: July 31, 2016
• Primary Completion: April 30, 2017
• Study Completion: November 14, 2017
• Last Updated: July 17, 2018
• Results First Posted: May 30, 2018

Record last verified: 2018-06

Locations

US (1); DE (1)