Safety and Efficacy study of M2951 in Subjects with Rheumatoid Arthritis

Phase 1

Conditions: Rheumatoid Arthritis
MedDRA version: 19.0Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2016-000064-42-SK

Lead Sponsor: Merck KGaA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 65

Inclusion Criteria

• 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 = 6 swollen joints (of 66 counted) and = 6 tender joints (of 68 counted)
• hsCRP = 3 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 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:
o Females who are postmenopausal (age-related amenorrhea = 12 consecutive months and increased follicle-stimulating hormone [FSH] > 40 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
o 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion Criteria

• 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 BTK inhibitors, or a biologic disease-modifying antirheumatic drug (DMARD; eg, anti-tumor necrosis factor alpha [anti-TNF-a], 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 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
• Active, clinically significant, viral, bacterial, or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks of Screening or during Screening, or completion of oral anti-infectives within 2 weeks before or during Screening, or a history of recurrent infections (ie, 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary.
• 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 mm, a positive QuantiFERON®-TB test or positive or borderline T-SPOT [Elispot] test); or positive QuantiFERON-TB test at Screening. Subjects with documented completed appropriate LTBI treatment would not be excluded and are not required to be tested.
o Subjects with current household contacts with active TB will also be excluded.
o 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 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 < 50% of the lower limit of normal at Screening
• Significant cytopenia including neutrophil count

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of M2951 in subjects with active RA on stable MTX therapy, as measured by the American College of Rheumatology (ACR) 20% (ACR20) response rate over a duration of 84 days.<br>;Secondary Objective: To assess the level of disease activity at 4 weeks in subjects with active RA as assessed by the percent change in high-sensitivity C-reactive protein (hsCRP) from Baseline to Day 29.<br>;Primary end point(s): The ACR20 response rate at Day 85.<br>;Timepoint(s) of evaluation of this end point: Day 85<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Percent change in hsCRP from Baseline to Day 29<br>;Timepoint(s) of evaluation of this end point: From Baseline to Day 29<br>

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