A randomized, double-blind, placebo-controlled phase 3 study to assess efficacy and safety of ropeginterferon alfa-2b in patients with early/lower-risk primary myelofibrosis.

Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with "early/lower-risk PMF", defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.

Validity of the estimated angular information obtained using an inertial motion capture system during standing trunk forward and backward bending.

BACKGROUND: Bending the trunk forward and backward while standing are common daily activities and can have various patterns. However, any dysfunction in these movements can considerably affect daily living activities. Consequently, a comprehensive evaluation of spinal motion during these activities and precise identification of any movement abnormalities are important to facilitate an effective rehabilitation. In recent years, with the development of measurement technology, the evaluation of movement patterns using an inertial motion capture system (motion sensor) has become easy. However, the accuracy of estimated angular information obtained via motion sensor measurements can be affected by angular velocity. This study aimed to compare the validity of estimated angular information obtained by assessing standing trunk forward and backward bending at different movement speeds using a motion sensor with a three-dimensional motion analysis system. METHODS: The current study included 12 healthy older men. A three-dimensional motion analysis system and a motion sensor were used for measurement. The participants performed standing trunk forward and backward bending at comfortable and maximum speeds, and five sensors were attached to their spine. Statistical analysis was performed using the paired t-test, intraclass correlation coefficient, mean absolute error, and multiple correlation coefficient. RESULTS: Results showed that the estimated angular information obtained using each motion sensor was not affected by angular velocity and had a high validity. CONCLUSIONS: Therefore, the angular velocity in this study can be applied clinically for an objective evaluation in rehabilitation.

Reliability and validity of estimated angles information assessed using inertial measurement unit-based motion sensors.

BACKGROUND: Inertial measurement unit (IMU)-based motion sensors are affordable, and their use is appropriate for rehabilitation. However, regarding the accuracy of estimated angle information obtained from this sensor, it is reported that it is likely affected by velocity. OBJECTIVE: The present study investigated the reliability and validity of the angle information obtained using IMU-based sensors compared with a three-dimensional (3D) motion analyzer. METHODS: The Euler angle obtained using the 3D motion analyzer and the angle obtained using the IMU-based sensor (IMU angle) were compared. Reliability was assessed by comparing the Bland-Altman analysis, intra-class correlation coefficient (ICC) (1,1), and cross-correlation function. The root mean square (RMS) error, ICC (2,1), and cross-correlation function were used to compare data on the Euler and IMU angles to evaluate the validity. RESULTS: Regarding reliability, the Bland-Atman analysis indicated no fixed or proportional bias in the angle measurements. The measurement errors ranged from 0.2° to 3.2°. In the validity, the RMS error ranged from 0.3° to 2.2°. The ICCs (2,1) were 0.9. The cross-correlation functions were >0.9, which indicated a high degree of agreement. CONCLUSION: The IMU-based sensor had a high reliability and validity. The IMU angle may be used in rehabilitation.

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.