Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as M2951 (BTK inhibitor), M2951 Low Dose, Evobrutinib, Ref (TF2), Evobrutinib MR-T1, Evobrutinib MR-T2, Evobrutinib MR-T3, Evobrutinib MR-T4
M2951 · 3 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.
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 | - |
| 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. |
| Evobrutinib: Normal Renal Function | EXPERIMENTAL | Subjects with estimated glomerular filtration rate (eGFR) greater than or equal to (\>=) 90 milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2) will receive a single oral dose of evobrutinib under fasting conditions. |
| Evobrutinib: Severe Renal Impairment | EXPERIMENTAL | Subjects with eGFR less than (\<) 30 mL/min/1.73 m\^2 will receive a single oral dose of evobrutinib under fasting conditions. |
| Evobrutinib: Moderate Renal Impairment | EXPERIMENTAL | Subjects with eGFR \>= to 30 mL/min/1.73 m\^2 and \< 60 mL/min/1.73 m\^2 will receive a single oral dose of evobrutinib under fasting conditions. |
| Evobrutinib: Mild Renal Impairment | EXPERIMENTAL | Subjects with eGFR \>= to 60 mL/min/1.73 m\^2 and \< 90 mL/min/1.73 m\^2 will receive a single oral dose of evobrutinib under fasting conditions. |
| 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. |
| M2951 (BTK inhibitor) | DRUG | Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1. |
| Evobrutinib | DRUG | Subjects will be administered a single oral dose of evobrutinib under fasting conditions. |
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 ...
Top 20 of 31 competitors
M2951 is an investigational small molecule developed by Merck KGaA (ticker MKGAF). It has been studied in hepatic impairment and rheumatoid arthritis. M2951 is a BTK inhibitor, and it remains in clinical development rather than being an approved medicine.
M2951 has been studied in rheumatoid arthritis, with a completed Phase 2 trial (NCT02784106) enrolling 65 participants in the United States and Germany. It is investigational and has not been established as a treatment for rheumatoid arthritis.
M2951 targets Bruton's tyrosine kinase, or BTK. It is a small molecule BTK inhibitor, a class of drug that acts on B cell signaling pathways. This mechanism underlies its study in rheumatoid arthritis and its evaluation in a hepatic impairment pharmacokinetic trial.
M2951 is developed by Merck KGaA, which trades under the ticker MKGAF. The company sponsored the clinical studies of M2951 in hepatic impairment and rheumatoid arthritis.
M2951 is in clinical development. A completed Phase 1 pharmacokinetic study (NCT04546789) evaluated the effect of hepatic impairment, and a completed Phase 2 study (NCT02784106) assessed safety and efficacy in rheumatoid arthritis. M2951 is investigational and is not an approved therapy.
M2951 has been evaluated in two completed trials: NCT04546789, a Phase 1 study of the effect of hepatic impairment on M2951 pharmacokinetics in Germany with 24 participants, and NCT02784106, a Phase 2 safety and efficacy study in rheumatoid arthritis with 65 participants.
Yes. M2951 is also referred to as M2951 (BTK inhibitor) and M2951 Low Dose. These names describe the same investigational small molecule BTK inhibitor developed by Merck KGaA, and searches using any of these terms refer to the same asset.