Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MSC2364447C, M2951, M2951 (BTK inhibitor), M2951 Low Dose, M2951 High Dose
Evobrutinib · 4 trials · 4 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.
TEAEs will be defined as the adverse events (AEs) that occur between first dose of study drug administration up to 4 weeks after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.
The severity of TEAEs will be graded using National cancer institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v 4.03) definitions of Grade 1 through Grade 5 following his/her best medical judgment. The severity of the AEs will be classified as follows: Grade 1 or mild, Grade 2 or moderate, Grade 3 or severe, Grade 4 or life-threatening and Grade 5 or death.
Clinical laboratory parameters being monitored for safety will be summarized using descriptive statistics, by postdose shifts relative to Baseline for relevant parameters using relevant cut-offs. Clinical significance will be determined by investigator.
Observed values and changes from Baseline in vital signs will be summarized for each treatment group using descriptive statistics. Clinically noteworthy changes in vital signs will be listed and summarized as appropriate. A semi-automated blood pressure and pulse rate recording device with an appropriate cuff size will be utilized. Blood pressure and pulse rate will be measured after 10 minutes' rest in the semi-supine position with the subject's arm unconstrained by clothing or other material. The blood pressure should be assessed on the same arm for each subject throughout the trial. Clinical significance will be determined by investigator.
Observed values and changes from Baseline in ECG will be summarized for each treatment group using descriptive statistics. Clinically noteworthy changes in ECG will be listed and summarized as appropriate. Clinical significance will be determined by investigator.
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 | - |
| MSC2364447C 25 mg | EXPERIMENTAL | - |
| MSC2364447C 75 mg | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| 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. |
| MSC2364447C | DRUG | Subjects will be administered with MSC2364447C 25 milligrams orally once daily for 4 weeks. |
| 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 ...
Evobrutinib has been studied in a Phase 1 pharmacokinetic trial evaluating how renal impairment affects the body's handling of the drug. The study enrolled 31 participants, including healthy volunteers, in Germany. Evobrutinib is an investigational agent and is not approved for treating renal impairment.
Evobrutinib targets Bruton's tyrosine kinase, or BTK, and acts as a BTK inhibitor. BTK is an enzyme involved in signaling pathways in certain immune and blood cells. In the renal impairment study, this targeted mechanism was evaluated for its pharmacokinetic behavior rather than for a therapeutic effect on kidney disease.
Evobrutinib is developed by Merck KGaA, which trades under the ticker MKGAF. The company sponsored the Phase 1 pharmacokinetic study of the drug in renal impairment conducted in Germany.
Evobrutinib is in Phase 1 development for renal impairment. The single completed trial, NCT03436394, was a Phase 1 pharmacokinetic study with 31 enrolled participants. Evobrutinib is investigational and has not been approved for any renal impairment indication.
Evobrutinib has been evaluated in one completed clinical trial, NCT03436394, titled Effect of Renal Impairment on Evobrutinib Pharmacokinetics. The Phase 1 study enrolled 31 participants in Germany, included healthy volunteers, and used a controlled design without randomization or double blinding. No active trials are currently listed.