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NCT02784106

Safety and Efficacy Study of M2951 in Participants With Rheumatoid Arthritis

Completed Phase 2 Results posted Last updated 17 July 2018
What this trial tests

Phase 2 trial testing Placebo in Rheumatoid Arthritis in 65 participants. Completed in 14 November 2017.

Timeline
31 July 2016
Primary endpoint
30 April 2017
14 November 2017

Quick facts

Lead sponsorEMD Serono Research & Development Institute, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment65
Start date31 July 2016
Primary completion30 April 2017
Estimated completion14 November 2017
Sites2 locations across United States, Germany

Drugs / interventions tested

Conditions studied

Sponsor

EMD Serono Research & Development Institute, Inc. — full company profile →

Who can join

Adults 18 to 75, any sex, with Rheumatoid Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Proportion of Participants Who Achieved American College of Rheumatology-20 (ACR20) Response Primary · 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 prote

GroupValue95% CI
Placebo: Double-Blind Treatment Period0.42
M2951: Double-Blind Treatment Period0.52
Mean Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Day 28 Secondary · Baseline, Day 28

Mean change in the hsCRP concentration from baseline at Day 28 was reported.

GroupValue95% CI
Placebo: Double-Blind Treatment Period-0.80± 2.00
M2951: Double-Blind Treatment Period-2.72± 1.93
Proportion of Participants Achieving American College of Rheumatology-50 (ACR50) Response Secondary · Day 28, Day 56 and Day 84

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.

Day 28
GroupValue95% CI
Placebo: Double-Blind Treatment Period0.10
M2951: Double-Blind Treatment Period0.06
Day 56
GroupValue95% CI
Placebo: Double-Blind Treatment Period0.23
M2951: Double-Blind Treatment Period0.18
Day 84
GroupValue95% CI
Placebo: Double-Blind Treatment Period0.23
M2951: Double-Blind Treatment Period0.21
Proportion of Participants Achieving American College of Rheumatology-70 (ACR70) Response Secondary · Day 28, Day 56 and Day 84

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.

Day 28
GroupValue95% CI
Placebo: Double-Blind Treatment Period0.00
M2951: Double-Blind Treatment Period0.06
Day 56
GroupValue95% CI
Placebo: Double-Blind Treatment Period0.03
M2951: Double-Blind Treatment Period0.06
Day 84
GroupValue95% CI
Placebo: Double-Blind Treatment Period0.13
M2951: Double-Blind Treatment Period0.09
Mean Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Day 84 Secondary · Baseline, Day 84

Mean change in the hsCRP concentration from baseline at Day 84 was reported.

GroupValue95% CI
Placebo: Double-Blind Treatment Period-2.14± 2.20
M2951: Double-Blind Treatment Period-3.54± 2.13
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 Secondary · Baseline, Day 28 and Day 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.

Change at Day 28
GroupValue95% CI
Placebo: Double-Blind Treatment Period-0.79± 0.14
M2951: Double-Blind Treatment Period-0.87± 0.13
Change at Day 84
GroupValue95% CI
Placebo: Double-Blind Treatment Period-1.35± 0.20
M2951: Double-Blind Treatment Period-1.28± 0.19
Proportion of Participants With Disease Activity Score- High Sensitivity C-Reactive Protein (DAS28-hsCRP) Value Less Than (<) 3.2 Secondary · Day 84

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.

GroupValue95% CI
Placebo: Double-Blind Treatment Period0.13
M2951: Double-Blind Treatment Period0.21
Proportion of Participants With Disease Activity Score- High Sensitivity C-Reactive Protein (DAS28-hsCRP) Value Less Than (<) 2.6 Secondary · Day 84

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.

GroupValue95% CI
Placebo: Double-Blind Treatment Period0.10
M2951: Double-Blind Treatment Period0.06
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Day 28 and 84 Secondary · Baseline, Day 28 and Day 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.

Change at Day 28
GroupValue95% CI
Placebo: Double-Blind Treatment Period-3± 36.9
M2951: Double-Blind Treatment Period-7± 22.1
Change at Day 84
GroupValue95% CI
Placebo: Double-Blind Treatment Period-3± 21.0
M2951: Double-Blind Treatment Period-9± 21.1
Change From Baseline in Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody Levels at Day 28 and 84 Secondary · Baseline, Day 28 and Day 84

Anti-cyclic citrullinated peptide (anti-CCP) is an antibody present in most rheumatoid arthritis participants.

Change at Day 28
GroupValue95% CI
Placebo: Double-Blind Treatment Period168± 991.1
M2951: Double-Blind Treatment Period-138± 720.9
Change at Day 84
GroupValue95% CI
Placebo: Double-Blind Treatment Period301± 1282.6
M2951: Double-Blind Treatment Period-396± 736.8
Change From Baseline in Rheumatoid Factor (RF) at Day 28 and 84 Secondary · Baseline, Day 28 and Day 84

Rheumatoid Factor is an anti-body present in the blood.

Change at Day 28
GroupValue95% CI
Placebo: Double-Blind Treatment Period-30± 124.2
M2951: Double-Blind Treatment Period-7± 59.7
Change at Day 84
GroupValue95% CI
Placebo: Double-Blind Treatment Period-34± 132.1
M2951: Double-Blind Treatment Period-26± 79.9
Change From Baseline in Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Day 84 Secondary · Baseline, 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).

GroupValue95% CI
Placebo: Double-Blind Treatment Period-21± 23.5
M2951: Double-Blind Treatment Period-24± 24.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Double-Blind Period: Baseline up to 16 weeks; Open-Label Period: Baseline up to 30 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo: Double-Blind Treatment Period
Serious: 0/32 (0%)
Deaths: 0/32
M2951: Double-Blind Treatment Period
Serious: 1/33 (3%)
Deaths: 0/33
Placebo/M2951: Open-Label Extension Period
Serious: 0/18 (0%)
Deaths: 0/18
M2951/M2951: Open-Label Extension Period
Serious: 0/21 (0%)
Deaths: 0/21

Serious adverse events (2 terms)

ReactionSystemPlacebo: Double-Blind Trea…M2951: Double-Blind Treatm…Placebo/M2951: Open-Label …M2951/M2951: Open-Label Ex…
Vestibular disorderEar and labyrinth disorders
Vertigo CNS originNervous system disorders
Other adverse events (20 terms — click to expand)

ReactionSystemPlacebo: Double-Blind Trea…M2951: Double-Blind Treatm…Placebo/M2951: Open-Label …M2951/M2951: Open-Label Ex…
Viral upper respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
NauseaGastrointestinal disorders
NasopharyngitisInfections and infestations
Lipase increasedInvestigations
Amylase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
VomitingGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
LeukocytosisBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Respiratory tract infectionInfections and infestations
GastroenteritisInfections and infestations
Blood glucose increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
Rheumatoid arthritisMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
HypertensionVascular disorders
AnxietyPsychiatric disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Vestibular disorder, Vertigo CNS origin.

Data from ClinicalTrials.gov NCT02784106 adverse events section.

Sponsor's own description

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).

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Small Molecule NF-κB Pathway Inhibitors in Clinic.
    Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
  2. Bruton's Tyrosine Kinase (BTK) Inhibitors and Autoimmune Diseases: Making Sense of BTK Inhibitor Specificity Profiles and Recent Clinical Trial Successes and Failures.
    Ringheim GE, Wampole M, Oberoi K. · · 2021 · cited 100× · PMID 34803999 · DOI 10.3389/fimmu.2021.662223
  3. Targeting Bruton's Tyrosine Kinase in Inflammatory and Autoimmune Pathologies.
    Neys SFH, Hendriks RW, Corneth OBJ. · · 2021 · cited 53× · PMID 34150760 · DOI 10.3389/fcell.2021.668131
  4. Bruton's Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease.
    Neys SFH, Rip J, Hendriks RW, Corneth OBJ. · · 2021 · cited 41× · PMID 34609725 · DOI 10.1007/s40265-021-01592-0
  5. Bruton's Tyrosine Kinase Inhibition for the Treatment of Rheumatoid Arthritis.
    Arneson LC, Carroll KJ, Ruderman EM. · · 2021 · cited 31× · PMID 34485183 · DOI 10.2147/itt.s288550
  6. Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19.
    Massalska M, Maslinski W, Ciechomska M. · · 2020 · cited 31× · PMID 32796683 · DOI 10.3390/cells9081876

Verify or expand the search:

Other trials of M2951

Trials testing the same drug.

Other recruiting trials for Rheumatoid Arthritis

Currently open trials in the same condition.

Other EMD Serono Research & Development Institute, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02784106.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing