Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
M2951 · 4 trials · 3 indications
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.
A linear mixed-effects model was used to analyze the relationship between evobrutinib and MSC2729909A concentrations and ΔQTc. Based on this model, drug-induced ΔΔQTc and its two-sided 90% CI was predicted over the clinical concentration range and at concentrations corresponding to the observed geometric mean Cmax following administration of 45 mg and 225 mg evobrutinib. The higher geometric mean Cmax calculated based on the PK and ECG Analysis Sets was considered.
AUC0-inf was calculated by combining AUC0-tlast and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Cmax was obtained directly from the plasma concentration versus time curve.
| Arm | Type | Description |
|---|---|---|
| Placebo: Double-Blind Treatment Period | PLACEBO_COMPARATOR | - |
| M2951: Double-Blind Treatment Period | EXPERIMENTAL | - |
| Placebo/M2951: Open Label Extension Period | EXPERIMENTAL | - |
| M2951/M2951: Open Label Extension Period | EXPERIMENTAL | - |
| Treatment Sequence 1 | EXPERIMENTAL | Participants will receive one of the four interventions in a sequence decided at randomization. |
| Treatment Sequence 2 | EXPERIMENTAL | Participants will receive one of the four interventions in a sequence decided at randomization. |
| Treatment Sequence 3 | EXPERIMENTAL | Participants will receive one of the four interventions in a sequence decided at randomization. |
| Treatment Sequence 4 | EXPERIMENTAL | Participants will receive one of the four interventions in a sequence decided at randomization. |
| Midazolam and/or M2951 | EXPERIMENTAL | - |
| Group 1: Normal Hepatic Function (Reference) | EXPERIMENTAL | Participants with normal hepatic function received single oral dose of 30 milligrams (mg) M2951 (3 film-coated tablets of 10 mg) on Day 1 after a standard breakfast. |
| Group 2: Mild Hepatic Impairment | EXPERIMENTAL | Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received single oral dose of 30 mg M2951 (3 film-coated tablets of 10 mg) on Day 1 after a standard breakfast. The Child-Pugh Score was a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon serum albumin, ascites, serum bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. |
| Group 3: Moderate Hepatic Impairment | EXPERIMENTAL | Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received single oral dose of 30 mg M2951 (3 film-coated tablets of 10 mg) on Day 1 after a standard breakfast. The Child-Pugh Score was a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon serum albumin, ascites, serum bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. |
| Name | Type | Description |
|---|---|---|
| Placebo | DRUG | Participants received placebo matched to M2951 twice daily up to Day 84 during the 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. |
| Placebo matched to M2951 | DRUG | Participants will receive single oral dose of placebo matched to M2951 in either of study periods (period 1 or period 2 or period 3 or period 4) under fasted conditions. |
| Moxifloxacin | DRUG | Participants will receive single oral dose of moxifloxacin in either of study periods (period 1 or period 2 or period 3 or period 4) under fasted conditions. |
| M2951 Low Dose | DRUG | Participants will receive single oral low dose of M2951 in either of study periods (period 1 or period 2 or period 3 or period 4) under fasted conditions. |
| M2951 High Dose | DRUG | Participants will receive single oral high dose of M2951 in either of study periods (period 1 or period 2 or period 3 or period 4) under fasted conditions. |
| Midazolam | DRUG | Participants will receive single oral dose of midazolam on Days 1, 3 and 13 under fed conditions. |
| M2951 (BTK inhibitor) | DRUG | Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1. |
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 ...
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M2951 is an investigational small molecule being studied for rheumatoid arthritis, hepatic impairment, and in healthy participants. It has been evaluated in clinical trials for these conditions, including a Phase 2 study in rheumatoid arthritis and Phase 1 studies in hepatic impairment and healthy volunteers.
M2951 is a Bruton's tyrosine kinase (BTK) inhibitor, as indicated by its clinical trial title. It is being developed to modulate BTK activity, which plays a role in immune cell signaling and inflammation, relevant to conditions like rheumatoid arthritis.
M2951 is being developed by Merck KGaA, a German multinational pharmaceutical company. The company's ticker symbol is MKGAF. Merck KGaA has sponsored clinical trials of M2951 across multiple countries, including the United States and Germany.
M2951 has completed Phase 1 and Phase 2 clinical trials. The most advanced study was a Phase 2 trial in rheumatoid arthritis, which has been completed. All trials listed for M2951 are completed, with no active trials currently ongoing.
M2951 has been studied in four completed clinical trials. These include NCT02784106, a Phase 2 study in rheumatoid arthritis; NCT04546789, a Phase 1 study in hepatic impairment; NCT04697511, a drug-drug interaction study in healthy participants; and NCT07214935, a thorough QT study in healthy participants.
Yes, M2951 is also known as evobrutinib. One clinical trial, NCT04697511, is titled 'Drug-drug Interaction Study of Evobrutinib With Midazolam in Healthy Participants,' confirming that M2951 and evobrutinib refer to the same investigational drug.