Extended Access Study of Momelotinib Dihydrochloride Monohydrate in Patients with Primary Myelofibrosis or Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis

The primary objective of this study is to provide extended access to **momelotinib** and assess its long-term safety in four cohorts of subjects with **Primary Myelofibrosis (PMF)** or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/ET MF). This is clinically relevant as it allows for the continued evaluation of momelotinib's safety profile in patients who have not experienced disease progression, thereby potentially improving management strategies for these conditions.

Secondary objectives include assessing overall survival (OS) and leukemia-free survival (LFS) in all subjects. These measures are critical for understanding the long-term efficacy of momelotinib in extending life expectancy and delaying disease progression in patients with myelofibrosis.

The clinical trial involves a total of **150 participants** diagnosed with **Primary Myelofibrosis (PMF)**, Post-polycythemia Vera, or Post-essential Thrombocythemia Myelofibrosis. The study population includes both male and female subjects, with an age range that spans from adults to the elderly. Participants were selected from those currently enrolled in specific ongoing studies, namely GS-US-352-0101, GS-US-352-1214, GS-US-352-1154, or SRA-MMB-301, and who have not experienced disease progression. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and ethical treatment. The selection criteria emphasize the continuation of momelotinib treatment, and participants must be able to comprehend and sign the informed consent form. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to provide extended access to **momelotinib dihydrochloride monohydrate** and assess its long-term safety in subjects with **primary myelofibrosis** (PMF) or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/ET MF). This is a Phase 4, randomized, double-blind, controlled trial. The trial is expected to run from March 1, 2018, to December 31, 2026. Participants will be divided into four cohorts based on their current enrollment in previous studies (GS-US-352-0101, GS-US-352-1214, GS-US-352-1154, or SRA-MMB-301) and will continue receiving treatment with momelotinib if they have not experienced disease progression.

The study involves several key visits, starting with an inclusion (screening) visit to confirm eligibility based on the principal inclusion criteria, which include current enrollment in one of the specified studies and the ability to comprehend and sign the informed consent form. Follow-up visits will be scheduled to monitor the incidence, severity, seriousness, and causal relationship of adverse events (AEs) as defined by CTCAE Version 4.03. Secondary endpoints include assessing overall survival (OS) and leukemia-free survival (LFS). The end-of-study visit will conclude the participant's involvement, ensuring all safety and efficacy data are collected.

Participant involvement is expected to last up to 84 days, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include disease progression or the occurrence of severe adverse events that compromise participant safety. The trial aims to ensure rigorous monitoring and data collection to evaluate the long-term safety and efficacy of momelotinib in the specified patient population.

The clinical trial involves the administration of **momelotinib dihydrochloride monohydrate**, an investigational medication developed by GlaxoSmithKline Research & Development Limited. This compound is provided in the form of a **tablet** and is intended for **oral use**. The maximum daily dose of momelotinib dihydrochloride monohydrate is 200 mg, with a total maximum dose of 504,000 mg over the course of the treatment period. The treatment duration is set for a maximum of 84 days. The active substance is of chemical origin, and the formulation is not designed for pediatric use. The medication is identified by the sponsor product code GSK3070785 and is classified as an orphan drug under the designation numbers EU/3/11/886;887;888.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on providing extended access to momelotinib and assessing its long-term safety in subjects with primary myelofibrosis or post-polycythemia vera or post-essential thrombocythemia myelofibrosis. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

The efficacy of the clinical trial will be assessed through the evaluation of secondary endpoints, specifically focusing on **overall survival (OS)** and **leukemia-free survival (LFS)**. These parameters will provide insights into the long-term benefits of the treatment with momelotinib dihydrochloride monohydrate in subjects with primary myelofibrosis (PMF) or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/ETMF). The collection and analysis of these efficacy parameters will be conducted in accordance with the trial's protocol, ensuring that the data is systematically gathered and evaluated to determine the treatment's impact on survival outcomes.