Safety and Efficacy Study of M2951 in Participants With Rheumatoid Arthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02784106
• Date of registration: 24/05/2016
• Prospective Registration: Yes
• Primary sponsor: EMD Serono Research & Development Institute, Inc.
• Public title: Safety and Efficacy Study of M2951 in Participants With Rheumatoid Arthritis
• Scientific title: Phase IIa Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of M2951 in Subjects With Rheumatoid Arthritis on Stable Methotrexate Therapy
• Date of first enrolment: July 31, 2016
• Target sample size: 65
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02784106
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Germany, United States

Contacts

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

Key inclusion & exclusion criteria

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 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.

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 Bruton's Tyrosine Kinase (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 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

- 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 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



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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Placebo

Drug: M2951

Primary Outcome(s)

Proportion of Participants Who Achieved American College of Rheumatology-20 (ACR20) Response [Time Frame: Day 84]

Secondary Outcome(s)

Absolute B-Cell Levels at Day 85 [Time Frame: Day 85]

Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Day 84 [Time Frame: Baseline, Day 84]

Change From Baseline in Rheumatoid Factor (RF) at Day 28 and 84 [Time Frame: Baseline, Day 28 and Day 84]

Number of Participants With Clinically Significant Vital Signs Abnormalities [Time Frame: Baseline up to 16 Weeks]

Proportion of Participants With Disease Activity Score- High Sensitivity C-Reactive Protein (DAS28-hsCRP) Value Less Than (<) 2.6 [Time Frame: Day 84]

Absolute Change From Baseline in B-cell Levels at Day 85 [Time Frame: Baseline, Day 85]

Absolute Change From Baseline in Immunoglobulin Levels at Day 85 [Time Frame: Baseline, Day 85]

Accumulation Ratio for Area Under the Concentration-Time Curve From Time Zero to 6 Hours (Racc [AUC0-6h]) of M2951 [Time Frame: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29]

Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Day 28 and 84 [Time Frame: Baseline, Day 28 and Day 84]

Change From Baseline in Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Day 84 [Time Frame: Baseline, Day 84]

Number of Participants With Grade 3 or Higher Clinically Significant Abnormality for Hematology, Biochemistry, Urinalysis or Coagulation [Time Frame: Baseline up to 16 Weeks]

Change From Baseline in Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody Levels at Day 28 and 84 [Time Frame: Baseline, Day 28 and Day 84]

Area Under the Concentration-Time Curve From Time Zero to 6 Hours (AUC 0-6h) of M2951 [Time Frame: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29]

Change From Baseline in Self-assessment of Pain Based on Visual Analog Scale (VAS) Score at Day 84 [Time Frame: 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 [Time Frame: Baseline, Day 28 and Day 84]

Mean Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Day 84 [Time Frame: Baseline, Day 84]

Plasma Concentration Observed Immediately Before Dosing on Day 29 (Cpre) of M2951 [Time Frame: Pre-dose on Day 29]

Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity [Time Frame: Baseline up to 16 Weeks]

Change From Baseline in Self-assessment of Disability Using Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Day 84 [Time Frame: Baseline, Day 84]

Absolute Immunoglobulin Levels at Day 85 [Time Frame: Baseline, Day 85]

Accumulation Ratio for Observed Maximum Plasma Concentration (Racc [Cmax]) of M2951 [Time Frame: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29]

Time to Reach Maximum Plasma Concentration (Tmax) of M2951 [Time Frame: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29]

Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings [Time Frame: Baseline up to 16 Weeks]

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time Frame: Baseline up to 16 Weeks]

Proportion of Participants Achieving American College of Rheumatology-50 (ACR50) Response [Time Frame: Day 28, Day 56 and Day 84]

Plasma Concentration of M2951 [Time Frame: Pre-dose at Day 1; 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29]

Mean Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Day 28 [Time Frame: Baseline, Day 28]

Proportion of Participants Achieving American College of Rheumatology-70 (ACR70) Response [Time Frame: Day 28, Day 56 and Day 84]

Maximum Observed Plasma Concentration (Cmax) of M2951 [Time Frame: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29]

Proportion of Participants With Disease Activity Score- High Sensitivity C-Reactive Protein (DAS28-hsCRP) Value Less Than (<) 3.2 [Time Frame: Day 84]

Secondary ID(s)

2016-000064-42

MS200527-0081

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck KGaA, Darmstadt, Germany

Results

• Results available: Yes
• Date Posted: 30/05/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02784106