A Multicenter, Randomized, Open-Label Study Comparing Romiplostim Plus Dexamethasone Versus Dexamethasone in Newly Diagnosed Primary Immune Thrombocytopenia

The primary objective of this study is to evaluate the **superiority** of romiplostim plus dexamethasone compared to dexamethasone alone in patients with newly diagnosed primary immune thrombocytopenia (**ITP**). The focus is on achieving a sustained response off any ITP treatment (6mSROT-50) without WHO grade 2 or more bleeding, assessed after 6 months (≥180 days) from treatment cessation. This is clinically relevant as it aims to establish a more effective treatment regimen for maintaining platelet levels and reducing bleeding risks in ITP patients.

Secondary objectives include: - Evaluating the difference between study arms in the proportion of patients achieving platelet counts ≥30x10⁹/L (SROT-30) or 50x10⁹/L (SROT-50) without any ITP treatment for at least 6 or 12 consecutive months and without WHO grade 2 or more bleeding. - Assessing the proportion of patients with complete response, response, global response, and targeted range, as well as early and initial response. - Comparing the time to loss of response (LoR) in patients who achieved response in both arms. - Comparing the proportion of patients requiring any rescue treatment during the study period. - Comparing the proportion of patients experiencing adverse events, including serious adverse events and laboratory safety parameters.

The clinical trial involves a total of **40 participants** diagnosed with **primary immune thrombocytopenia** (ITP). The study population includes both male and female subjects, aged 18 years and older, who have been newly diagnosed with ITP and have not received prior treatment for this condition. Participants were selected based on specific criteria, including a platelet count of less than 30x10⁹/L or ITP with platelet counts below 50x10⁹/L accompanied by bleeding symptoms. Additionally, eligible participants must have a serum creatinine concentration of 1.5 mg/dL or lower. The trial does not include any vulnerable populations. Lifestyle factors such as diet, physical activity, or habits were not specified as part of the selection criteria. The study aims to assess the efficacy of romiplostim combined with dexamethasone compared to dexamethasone alone in achieving a sustained response in ITP patients after six months of treatment cessation, without significant bleeding events.

The clinical trial is designed to evaluate the **superiority** of a combination treatment of **romiplostim** plus **dexamethasone** compared to **dexamethasone** alone in patients with newly diagnosed primary immune thrombocytopenia. This is a multicenter, randomized, open-label study. The trial aims to assess the sustained response off any immune thrombocytopenia treatment and without WHO grade 2 or more bleeding after six months from treatment cessation. The study is expected to conclude by September 2026, with recruitment having commenced in December 2022.

Participants will be randomly assigned to one of the two treatment arms. The trial will involve several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, platelet counts, and serum creatinine concentration. Following randomization, participants will undergo regular follow-up visits to monitor treatment efficacy and safety. The primary endpoint will be evaluated at six months, with secondary endpoints assessed at both six and twelve months post-treatment cessation. The end-of-study visit will mark the conclusion of participant involvement, which is anticipated to last up to 12 months.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it in the participant's best interest. The trial will ensure rigorous monitoring to maintain participant safety and data integrity throughout the study duration.

The clinical trial involves the administration of **romiplostim**, marketed under the name Nplate, which is provided in two formulations: 500 micrograms powder and solvent for solution for injection, and 250 micrograms powder for solution for injection. Both formulations are intended for **subcutaneous use**. The pharmaceutical form of the 500 micrograms product is a solution for injection, while the 250 micrograms product is a powder for injection. The maximum daily dose for both formulations is 10 µg/kg, with a total maximum dose of 10 µg/kg. The treatment period for romiplostim is up to 48 weeks. Romiplostim is a protein-based therapeutic agent developed by Amgen Europe B.V., and it is classified under the ATC code B02BX04.

In addition to romiplostim, the trial includes the administration of **dexamethasone phosphate**, a chemical substance, which serves as a comparator treatment. Dexamethasone is administered orally, with a maximum daily dose of 40 mg and a total maximum dose of 160 mg. The treatment period for dexamethasone is up to 4 weeks. The pharmaceutical form of dexamethasone is denoted as PHF00075MIG. Dexamethasone is classified under the ATC code S01BA01 and is also developed by Amgen Europe B.V.

Participant compliance with the dosing schedules will be monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to evaluate the superiority of romiplostim in combination with dexamethasone versus dexamethasone alone in patients with newly diagnosed primary immune thrombocytopenia, focusing on sustained response and bleeding outcomes.

The efficacy of the clinical trial will be assessed by evaluating the superiority of **romiplostim** plus dexamethasone versus dexamethasone alone in patients with newly diagnosed primary immune thrombocytopenia (ITP). The primary endpoint is the proportion of patients achieving a sustained response off any ITP treatment (6mSROT-50) at 6 months (180 days) from treatment cessation. This is defined as having platelet counts higher or equal to 50x10⁹/L without any ITP treatment, including rescue treatment, for at least 6 consecutive months and without WHO grade 2 or more bleeding.

Secondary endpoints include the proportion of patients achieving 6mSROT-30 at 6 months, 12mSROT-50 at 12 months (365 days), and 12mSROT-30 at 12 months from treatment cessation. These endpoints will be measured to compare the efficacy between the study arms. The trial is designed to provide a comprehensive evaluation of the treatment's efficacy over a specified period, ensuring a robust analysis of the therapeutic benefits of the combination treatment compared to dexamethasone alone.