Evaluation of Peginterferon Alfa-2a and Ruxolitinib Combination Therapy in Newly Diagnosed Polycythemia Vera Patients: A Danish Safety and Efficacy Study

The primary objective of this study is to evaluate the **safety profile** of combination therapy with Interferon-Alpha2a and Ruxolitinib in patients with **polycythemia vera** over a 24-month period. This is clinically relevant as it aims to determine the long-term safety of this therapeutic regimen, which could potentially offer a new treatment option for managing this condition.

Secondary objectives include assessing the safety profile of the combination therapy after 12 months, as measured by adverse events (AEs), serious adverse events (SAEs), and withdrawals due to AEs/SAEs. Additionally, the study will evaluate the efficacy profile by examining the normalization of red blood cell values, white blood cell counts, and platelet counts. Other efficacy measures include response rates, changes in the JAK2V617F allele burden, the proportion of patients experiencing thrombosis and/or hemorrhage, the proportion of patients achieving no need for phlebotomies, achieving normal spleen size, and the progression of disease. Progression-free survival will also be assessed. These secondary objectives are crucial for understanding the broader impact of the therapy on disease management and patient outcomes.

The clinical trial focuses on evaluating the **safety profile** of COMBI therapy in patients diagnosed with **polycythemia vera** over a 24-month period. The study population includes both male and female participants aged 18 years and older. Participants are required to have a confirmed diagnosis of polycythemia vera according to the WHO 2016 criteria and must test negative for active or latent tuberculosis. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. Key inclusion criteria involve biochemical evidence of active disease, hypermetabolic symptoms, pruritus, symptomatic splenomegaly, or a history of thrombosis. The selection process for the trial population is not detailed in the provided information.

The clinical trial is designed to evaluate the **safety** and efficacy of combination therapy using **peginterferon alfa-2a** and **ruxolitinib** in patients newly diagnosed with **polycythemia vera**. This is a Phase 4, randomized, double-blind, controlled trial with an estimated duration of 24 months for each participant. The trial aims to assess the safety profile of the combination therapy over a 24-month period, with primary endpoints focusing on adverse events and serious adverse events. Secondary endpoints include the proportion of patients achieving complete hematological remission and the measurement of JAK2V617F allele burden at various intervals.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, confirmed diagnosis of polycythemia vera, and a negative test for active or latent tuberculosis. Follow-up visits will occur at 3, 6, 8, 9, 12, 18, and 24 months to monitor safety and efficacy outcomes. The end-of-study visit will conclude the participant's involvement, with data collection on the final safety and efficacy measures.

The expected length of participant involvement is 24 months, with conditions for early termination including withdrawal due to adverse events or serious adverse events. Participants will receive **peginterferon alfa-2a** via subcutaneous injection and **ruxolitinib** orally, with maximum daily doses of 19.57 µg and 40 mg, respectively. The trial is not categorized as low intervention and is exploratory in nature, focusing on the combination therapy's potential benefits in treating polycythemia vera.

The clinical trial involves the administration of **PEGINTERFERON ALFA-2A**, a **solution for injection**. This experimental medication is administered via the **subcutaneous** route. The maximum daily dose is 19.57 µg, with a total maximum dose of 14,286.1 µg over a treatment period of 24 months. **Peginterferon alfa-2a** is a protein-based therapeutic agent, specifically categorized under proteins of other origins. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.

In addition to the experimental medication, the trial includes the use of **Jakavi 5 mg tablets**, which contain the active substance **RUXOLITINIB**. This medication is administered orally, with a maximum daily dose of 40 mg and a total maximum dose of 29,200 mg over the same 24-month treatment period. **Ruxolitinib** is a chemically derived substance, and its administration is also closely monitored to ensure participant compliance with the prescribed dosing schedule. Both medications are used in combination to evaluate their safety and efficacy in patients newly diagnosed with **polycythemia vera**. The trial does not include any placebo or comparator treatments, focusing solely on the combination therapy of these two active substances.

The efficacy of the combination therapy with **peginterferon alfa-2a** and **ruxolitinib** in patients with polycythemia vera will be assessed through several secondary endpoints. These include the proportion of patients achieving complete hematological remission, defined as hematocrit (HCT) less than 45, platelet count (PLA) less than or equal to 400, and white blood cell count (WBC) less than 10, at multiple timepoints: 3, 6, 8, 9, 12, 18, and 24 months. Additionally, remission rates will be evaluated at 12 and 24 months.

Another key efficacy parameter is the measurement of the JAK2V617F allele burden, which will be assessed at baseline and subsequently at 3, 6, 12, and 24 months. The proportion of patients experiencing thrombosis and/or hemorrhage will also be monitored at 12 and 24 months. These efficacy assessments will provide comprehensive insights into the therapeutic impact of the combination treatment over the course of the trial.