Rheumatoid ArthritisPhase 2NCT02784106
Safety and Efficacy Study of M2951 in Participants With Rheumatoid Arthritis
A Phase 2 study testing M2951 in people with Rheumatoid Arthritis, run by EMD Serono Research & Development Institute, Inc. at 2 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- M2951
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 31 Jul 2016to 14 Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official 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
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
- Being tested
- Placebo, M2951
- Keywords
- Rheumatoid Arthritis, M2951, Bruton's Tyrosine Kinase (BTK)
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Participants received placebo matched to M2951 twice daily up to Day 84 during the double-blind treatment period.
M2951Drug
Also called Evobrutinib
Participants received 50 milligrams (mg) M2951 orally twice daily up to Day 84 during the double-blind treatment period.
M2951Drug
Also called Evobrutinib
Participants who received placebo matched to M2951 or M2951 in double-blind treatment period, received 50 mg M2951 orally twice daily up to 26-weeks during the open label extension period.
| Study group | Role | What they receive |
|---|---|---|
| Placebo: Double-Blind Treatment Period | Placebo comparator | Not described Receives: Drug: Placebo |
| M2951: Double-Blind Treatment Period | Experimental | Not described Receives: Drug: M2951 |
| Placebo/M2951: Open Label Extension Period | Experimental | Not described Receives: Drug: M2951 |
| M2951/M2951: Open Label Extension Period | Experimental | Not described Receives: Drug: M2951 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 84
Secondary outcomes (30)
Mean Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Day 28
Mean change in the hsCRP concentration from baseline at Day 28 was reported.
Measured: Baseline, Day 28
Proportion of Participants Achieving American College of Rheumatology-50 (ACR50) Response
ACR 50 response: >=50% 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 >=50% 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 HAQ-DI; and 5) acute phase reactant as measured by hsCRP. Proportion of ACR50 responders = Number of participants with ACR50 response divided by total participants.
Measured: Day 28, Day 56 and Day 84
Proportion of Participants Achieving American College of Rheumatology-70 (ACR70) Response
ACR 70 response: >=70% 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 >=70% 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 HAQ-DI; and 5) acute phase reactant as measured by hsCRP. Proportion of ACR70 responders = Number of participants with ACR70 response divided by total participants.
Measured: Day 28, Day 56 and Day 84
Mean Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Day 84
Mean change in the hsCRP concentration from baseline at Day 84 was reported.
Measured: 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
Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28)+ 0.014* participant's global assessment of disease activity + 0.36*natural log(hsCRP+1) +0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
Measured: Baseline, Day 28 and Day 84
Proportion of Participants With Disease Activity Score- High Sensitivity C-Reactive Protein (DAS28-hsCRP) Value Less Than (<) 3.2
DAS28-hsCRP consisted of composite score of following variables: TJC28, SJC28, hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP =0.56* sqrt(TJC28) + 0.28*sqrt(SJC28)+ 0.014* participant's global assessment of disease activity + 0.36*natural log(hsCRP+1) +0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity. Proportion of participants with DAS28-hsCRP value <3.2 were reported.
Measured: Day 84
Proportion of Participants With Disease Activity Score- High Sensitivity C-Reactive Protein (DAS28-hsCRP) Value Less Than (<) 2.6
DAS28 consisted of composite score of following variables: TJC28, SJC28, hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP =0.56* sqrt (TJC28) + 0.28*sqrt (SJC28)+ 0.014* participant's global assessment of disease activity + 0.36*natural log(hsCRP+1) +0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity. Proportion of participants with DAS28-hsCRP value <2.6 were reported.
Measured: Day 84
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Day 28 and 84
Erythrocyte sedimentation rate (ESR) is a type of blood test that measures how quickly erythrocytes (red blood cells) settle at the bottom of a test tube that contains a blood sample. Higher values indicate inflammation in the body.
Measured: Baseline, Day 28 and Day 84
Change From Baseline in Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody Levels at Day 28 and 84
Anti-cyclic citrullinated peptide (anti-CCP) is an antibody present in most rheumatoid arthritis participants.
Measured: Baseline, Day 28 and Day 84
Change From Baseline in Rheumatoid Factor (RF) at Day 28 and 84
Rheumatoid Factor is an anti-body present in the blood.
Measured: 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
The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).
Measured: Baseline, Day 84
Change From Baseline in Self-assessment of Pain Based on Visual Analog Scale (VAS) Score at Day 84
The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.
Measured: Baseline, Day 84
Change From Baseline in Self-assessment of Disability Using Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Day 84
The HAQ-DI questionnaire assessed the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Measured: Baseline, Day 84
Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Day 84
The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).
Measured: Baseline, Day 84
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. TEAEs included both Serious TEAEs and non-serious TEAEs.
Measured: Baseline up to 16 Weeks
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Grade 3 and 4 TEAES as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03) were presented. Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL).Grade 4 refers to Life-threatening consequences; where urgent intervention indicated.
Measured: Baseline up to 16 Weeks
Number of Participants With Grade 3 or Higher Clinically Significant Abnormality for Hematology, Biochemistry, Urinalysis or Coagulation
Clinically significant abnormalities for hematology, biochemistry or coagulation were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 toxicity grades, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death. Participants with grade 3 or higher were reported.
Measured: Baseline up to 16 Weeks
Number of Participants With Clinically Significant Vital Signs Abnormalities
Vital sign assessment included blood pressure, pulse rate, respiratory rate and temperature. Clinical significance was determined by the investigator.
Measured: Baseline up to 16 Weeks
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
The 12-lead ECG recordings were obtained after 10 minutes of rest in a semi-supine position. The ECG parameters obtained directly from the computerized 12-lead ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, and QT interval. Clinical significance was determined by the investigator.
Measured: Baseline up to 16 Weeks
Plasma Concentration of M2951
Measured: 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
Area Under the Concentration-Time Curve From Time Zero to 6 Hours (AUC 0-6h) of M2951
Measured: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29
Maximum Observed Plasma Concentration (Cmax) of M2951
Measured: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29
Plasma Concentration Observed Immediately Before Dosing on Day 29 (Cpre) of M2951
Measured: Pre-dose on Day 29
Time to Reach Maximum Plasma Concentration (Tmax) of M2951
Measured: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29
Accumulation Ratio for Area Under the Concentration-Time Curve From Time Zero to 6 Hours (Racc [AUC0-6h]) of M2951
Accumulation ratio for AUC was calculated as AUC 0-6h, Day 29 divided by AUC 0-6h, Day 1
Measured: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29
Accumulation Ratio for Observed Maximum Plasma Concentration (Racc [Cmax]) of M2951
Accumulation ratio for Cmax , was calculated as Cmax, Day 29 divided by Cmax, Day1
Measured: Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0 hours post-dose at Day 1 and Day 29
Absolute Immunoglobulin Levels at Day 85
Following immunoglobulin levels were measured: Immunoglobulin A , Immunoglobulin G, Immunoglobulin G Subclass 1, Immunoglobulin G Subclass 2, Immunoglobulin G Subclass 3, Immunoglobulin G Subclass 4, Immunoglobulin M.
Measured: Baseline, Day 85
Absolute Change From Baseline in Immunoglobulin Levels at Day 85
Following immunoglobulin levels were measured: Immunoglobulin A , Immunoglobulin G, Immunoglobulin G Subclass 1, Immunoglobulin G Subclass 2, Immunoglobulin G Subclass 3, Immunoglobulin G Subclass 4, Immunoglobulin M.
Measured: Baseline, Day 85
Absolute B-Cell Levels at Day 85
Measured: Day 85
Absolute Change From Baseline in B-cell Levels at Day 85
Measured: Baseline, Day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2016 (estimated)
- Study start31 Jul 2016
- Primary completion30 Apr 2017
- Study completion14 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by EMD Serono Research & Development Institute, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02784106
- Sponsor's protocol ID
- MS200527-0081
- Other IDs
- 2016-000064-42, 2016
- Status last verified
- Jun 2018
- First submitted
- 24 May 2016
- Last updated
- 17 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02784106
- Acronym / sponsor ID
- MS200527-0081
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, M2951, Bruton's Tyrosine Kinase (BTK)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- EMD Serono Research & Development Institute, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 31 Jul 2016 (actual)
- Primary completion
- 30 Apr 2017 (actual)
- Study completion
- 14 Nov 2017 (actual)
- First posted
- 26 May 2016 (estimated)
- Results
- Posted 30 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboParticipants received placebo matched to M2951 twice daily up to Day 84 during the double-blind treatment period. | Drug | Placebo: Double-Blind Treatment Period |
| M2951Also: EvobrutinibParticipants received 50 milligrams (mg) M2951 orally twice daily up to Day 84 during the double-blind treatment period. | Drug | M2951: Double-Blind Treatment Period |
| M2951Also: EvobrutinibParticipants who received placebo matched to M2951 or M2951 in double-blind treatment period, received 50 mg M2951 orally twice daily up to 26-weeks during the open label extension period. | Drug | M2951/M2951: Open Label Extension Period, Placebo/M2951: Open Label Extension Period |
Primary outcome
Proportion of Participants Who Achieved American College of Rheumatology-20 (ACR20) Response
Time frame: Day 84
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.
30 secondary outcomes
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-50 (ACR50) Response
Time frame: Day 28, Day 56 and Day 84
Proportion of Participants Achieving American College of Rheumatology-70 (ACR70) Response
Time frame: Day 28, Day 56 and Day 84
Mean Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) 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
Proportion of Participants With Disease Activity Score- High Sensitivity C-Reactive Protein (DAS28-hsCRP) Value Less Than (<) 3.2
Time frame: Day 84
Proportion of Participants With Disease Activity Score- High Sensitivity C-Reactive Protein (DAS28-hsCRP) Value Less Than (<) 2.6
Time frame: Day 84
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 Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody Levels at Day 28 and 84
Time frame: Baseline, Day 28 and Day 84
Change From Baseline in Rheumatoid Factor (RF) 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
Change From Baseline in Self-assessment of Pain Based on Visual Analog Scale (VAS) Score at Day 84
Time frame: Baseline, Day 84
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
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
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to 16 Weeks
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Time frame: Baseline up to 16 Weeks
Number of Participants With Grade 3 or Higher Clinically Significant Abnormality for Hematology, Biochemistry, Urinalysis or Coagulation
Time frame: Baseline up to 16 Weeks
Number of Participants With Clinically Significant Vital Signs Abnormalities
Time frame: Baseline up to 16 Weeks
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
Time frame: Baseline up to 16 Weeks
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
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
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
Plasma Concentration Observed Immediately Before Dosing on Day 29 (Cpre) of M2951
Time frame: Pre-dose on 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
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
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
Absolute Immunoglobulin Levels at Day 85
Time frame: Baseline, Day 85
Absolute Change From Baseline in Immunoglobulin Levels at Day 85
Time frame: Baseline, Day 85
Absolute B-Cell Levels at Day 85
Time frame: Day 85
Absolute Change From Baseline in B-cell Levels at Day 85
Time frame: Baseline, Day 85
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing M2951 in people with Rheumatoid Arthritis, run by EMD Serono Research & Development Institute, Inc. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Who Achieved American College of Rheumatology-20 (ACR20) Response (time frame: Day 84). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2018.