Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 3:27 PM
Ignite Modification Date:
2025-12-24 @ 3:27 PM
NCT ID:
NCT05753592
Brief Summary:
This was a Phase 1, open-label study to evaluate the PK, safety, and tolerability after administration of multiple doses of remibrutinib in participants with mild, moderate, or severe hepatic impairment (HI) compared to pooled matched healthy control participants with normal hepatic function.
Detailed Description:
This study was conducted in 2 parts. Part 1 was comprised of participants with mild (Child Pugh A; Group 1) and moderate (Child-Pugh B; Group 2) HI and matched healthy control participants with normal hepatic function (Group 4). Groups 1 and 2 were enrolled in parallel. Part 2 was comprised of participants with severe HI (Child-Pugh C; Group 3) and matched healthy control participants with normal hepatic function (Group 4). Matched healthy control participants (Group 4) were enrolled in parallel to Parts 1 and 2.
Up to 48 male and female participants, aged 18 to 70 years inclusive, were planned to be enrolled, with 8 participants enrolled in each of the mild (Child-Pugh A; Group 1 in Part 1), moderate (Child Pugh B; Group 2 in Part 1), and severe (Child-Pugh C; Group 3 in Part 2) HI groups, and up to 24 participants planned to be enrolled in the matched healthy control group (Group 4 from Parts 1 and 2). Additional participant(s) may have been enrolled if a participant discontinued from the study before completion of the PK assessment to ensure that at least 6 participants in each group completed the scheduled PK assessments. Due to difficulties in enrolling severe HI participants, only 7 severe HI participants were enrolled in this study.
Each study part was comprised of a screening period of up to 28 days (Day -29 to Day -2), a Baseline evaluation on Day -1, and a treatment period including up to 8 days of safety and PK data collection. Participants who met the eligibility criteria at Screening were admitted for Baseline evaluations on Day 1. Baseline safety assessments were performed prior to first dosing of study treatment. Participants were domiciled from Day -1 through Day 8.
All participants received 25 mg remibrutinib b.i.d. orally under fasting conditions on Days 1 and 2, and a morning oral dose of 25 mg remibrutinib on Day 3. PK samples were collected predose on Day 3 and until 72 hours post Day 3 dosing. Throughout the study, safety assessments included physical examinations, electrocardiograms (ECGs), vital signs, clinical laboratory evaluations (hematology, chemistry, urinalysis, and coagulation), and AE/serious adverse event (SAE) monitoring.
The investigator and Novartis conducted a joint interim review of safety and PK data from Part 1 before proceeding to Part 2. Data from at least 4 participants with mild HI (Group 1), 4 participants with moderate HI (Group 2), and their matched healthy control participants (Group 4), who completed PK study assessments up to Day 6 in Part 1, were evaluated.
Part 2 only began after administration of remibrutinib in the 4 evaluable participants from each of the mild and moderate HI groups (Groups 1 and 2) and their matched healthy control participants (Group 4) in Part 1 was deemed safe and tolerable based on the interim review by the investigator and Novartis. Depending on the outcome of the interim review, administration of a lower dose of remibrutinib in severe HI participants (Group 3) and their matched healthy control participants was to be considered. However, upon review of the interim data, the decision was made to not change the dose for severe HI participants.
As per the current study protocol, study drug strengths available for this trial were 25 mg and 10 mg. Therefore, the lowest dose that could have been used in Part 2 was 10 mg b.i.d. At the time of the interim data review, a decision was to be made as to whether or not to reduce the Part 2 dose, based on observed PK exposures and safety assessments in Part 1 and predicted exposures in severe HI participants in Part 2. In this particular case, Part 2 was to be initiated after the submission and approval of a Substantial Amendment from the respective Health Authorities (HA) and Ethics Committee (EC) were obtained. A decision was made to proceed with Part 2 using the same 25 mg dose as in Part 1.
Study Completion evaluations occurred on Day 8, followed by a post-study safety follow-up contact (e.g., follow-up telephone call, e-mail) approximately 30 days after last administration of study treatment. The information collected during the follow-up contact was kept as source documentation. The study was considered completed once all the participants finished the required assessments.
The total study duration for each participant was expected to be up to approximately 62 days, including the Screening period and the follow-up contact.
Study:
NCT05753592
Study Brief:
Protocol Section:
NCT05753592