Phase 1/2 Study on Safety and Pharmacokinetics of Rilzabrutinib in Relapsed Immune Thrombocytopenia Patients

The primary objective of this study is to evaluate the **safety** and **tolerability** of rilzabrutinib, an oral BTK inhibitor, in patients with **Immune Thrombocytopenia** (ITP). This includes assessing up to four dose levels in Part A and a 400 mg BID dose in Part B. Additionally, the study aims to explore the clinical activity and durability of response of rilzabrutinib in relapsed or refractory ITP patients, as well as to evaluate the platelet response during the first 8 weeks of treatment. These objectives are clinically relevant as they aim to determine the optimal dosing and therapeutic potential of rilzabrutinib in managing ITP, a condition characterized by low platelet counts and increased bleeding risk.

Secondary objectives include characterizing the **pharmacokinetics** of rilzabrutinib in patients with ITP in both Part A and Part B of the study. Understanding the pharmacokinetics is crucial for optimizing dosing regimens and ensuring effective and safe treatment outcomes.

The clinical trial involves a total of **71 participants** diagnosed with **Immune Thrombocytopenia** (ITP). The study population comprises both male and female patients, aged between 18 to 80 years, who have either primary or secondary immune-related ITP. Participants were selected based on their relapsed or refractory status to prior therapies. The trial includes individuals from a vulnerable population, ensuring a comprehensive assessment of the investigational treatment's safety and efficacy. Lifestyle factors such as diet, physical activity, or habits were not specified in the available data. The selection criteria focused on the inclusion of adults within the specified age range, without any additional lifestyle considerations mentioned.

The clinical trial is designed to evaluate the **safety**, pharmacokinetics, and clinical activity of **rilzabrutinib**, an oral BTK inhibitor, in patients with **immune thrombocytopenia** (ITP). This study is structured as an adaptive, open-label, dose-finding trial, encompassing both Phase 1 and Phase 2 components. The trial is expected to conclude by December 31, 2025, with recruitment having commenced on March 20, 2018. Participants will be involved in the study for a duration that aligns with the trial's objectives, with specific conditions outlined for early termination, such as the occurrence of treatment-emergent adverse events (TEAEs).

The trial is divided into two parts: Part A and Part B. Part A aims to characterize the safety and tolerability of up to four dose levels of rilzabrutinib, as well as to explore its clinical activity in relapsed or refractory ITP patients. Part B focuses on the safety and tolerability of a 400 mg BID dose, further exploring the clinical activity and durability of response, and evaluating the platelet response within the first 8 weeks of treatment. The primary endpoints include the incidence of TEAEs and platelet count increases, while secondary endpoints assess various platelet count metrics and the use of rescue medication.

Study visits are sequenced to ensure comprehensive data collection and participant safety. The inclusion visit, or screening, will determine eligibility based on criteria such as age (18 to 80 years) and diagnosis of immune-related ITP. Follow-up visits will monitor safety, tolerability, and efficacy, with assessments of platelet counts and adverse events. The end-of-study visit will conclude the participant's involvement, summarizing the treatment outcomes and any long-term effects. Participants may be withdrawn from the study if they experience significant adverse events or fail to comply with the study protocol.

**Rilzabrutinib** is the experimental medication being evaluated in this clinical trial. It is a synthetically manufactured **Bruton's tyrosine kinase (BTK) inhibitor** developed by Principia Biopharma, Inc. The pharmaceutical form of Rilzabrutinib is a **tablet**, and it is administered orally. The study involves an adaptive, open-label, dose-finding approach to assess the safety, pharmacokinetics, and clinical activity of Rilzabrutinib in patients with relapsed **immune thrombocytopenia (ITP)**. The trial is structured in two parts: Part A explores up to four dose levels, while Part B focuses on a fixed dose of 400 mg administered twice daily (BID). The primary objective is to evaluate the safety and tolerability of Rilzabrutinib, as well as its clinical activity and durability of response in patients who have relapsed or have an insufficient response to prior therapies.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial is designed to monitor participant compliance with the dosing schedule, ensuring that the administration of Rilzabrutinib is consistent with the study protocol. The study aims to evaluate the platelet response to Rilzabrutinib therapy during the first 8 weeks of active treatment, which is critical for achieving the primary endpoint. The trial does not include a pediatric formulation, and the medication is classified as an orphan drug, indicating its use in treating a rare condition.

The clinical trial aims to assess the efficacy of **Rilzabrutinib**, an oral BTK inhibitor, in patients with relapsed immune thrombocytopenia (ITP). Efficacy will be evaluated through both primary and secondary endpoints. The primary endpoints include the incidence of treatment-emergent adverse events (TEAEs) and platelet count responses. Specifically, Part A will focus on consecutive increased platelet counts, while Part B will assess sustained increases in platelet counts.

Secondary endpoints will further explore platelet count dynamics and patient outcomes. These include the percentage of weeks with platelet counts ≥ 50,000/μL, the proportion of patients achieving specific platelet count thresholds, and changes from baseline in platelet counts. Additionally, the trial will evaluate the number of weeks with platelet counts ≥ 50,000/μL or ≥ 30,000/μL, time to first platelet count ≥ 50,000/μL, and the proportion of patients requiring rescue medication. The ITP Bleeding Assessment Tool (ITP-BAT) will be used to assess changes in bleeding events.

Data collection will occur at various timepoints throughout the study, with specific attention to the first 8 weeks of active treatment in Part B. The trial will also measure plasma pharmacokinetic parameters of **Rilzabrutinib** to support the evaluation of its clinical activity and durability of response. The study is designed to provide comprehensive insights into the efficacy of **Rilzabrutinib** in managing relapsed ITP, with a focus on both safety and clinical outcomes.