Polycythemia Vera
Conditions
Brief summary
The goal of this clinical trial is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of 9MW3011 in Chinese patients with Polycythemia Vera（PV）.
Detailed description
The multiple dose fo the starting dose cohorts will comprise 3 dose cohorts of 8 PV subjects each.In each cohort, subjects will receive 9MW3011 via intravenous infusion.A decision on whether to proceed with case expansion and dose escalation will be based on the safety and PK-PD data.
Interventions
DRUG9MW3011
Multiple dose
Sponsors
Mabwell (Shanghai) Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female patients aged 18 years or older at the time of screening. 2. A confirmed diagnosis of PV according to the revised 2016 World Health Organization criteria and are resistant to or intolerant of hydroxyurea or Interferon alpha. 3. Have a treatment history for PV with resistance or intolerance to hydroxyurea or Interferon alpha. 4. Subjects receiving hydroxyurea, Interferon alpha, or ruxolitinib must complete a washout period before administration of the investigational drug. 5. Must agree to adhere to appropriate contraception requirements during the study period. 6. All female subjects with fertility capacity tested negative for blood pregnancy. 7. Voluntarily participate in clinical trials and agrees to participate in the study by giving written informed consent.
Exclusion criteria
1. The spleen is palpable at least 5 centimeters below the left costal margin upon palpation at baseline. 2. Heart failure, unstable angina pectoris, myocardial infarction, and other thrombotic diseases within the 6 months prior to screening. 3. Abnormal QTc interval of electrocardiogram within the 6 months prior to screening. 4. Uncontrolled hypertension prior to screening. 5. Any non-PV myeloproliferative neoplasms (MPN). 6. Blast cells and blast granulocytes in the peripheral blood within the 3 months prior to screening. 7. Hematological indicators do not meet the requirements at the time of screening. 8. Known positive for active hepatitis B, hepatitis C, syphilis or human immunodeficiency virus (HIV) infection. 9. History of invasive malignancies within the last 5 years. 10. Severe infection or uncontrolled active infection. 11. Other hematological and lymphatic system diseases or any diseases causing hemolysis or erythrocyte instability. 12. Other systemic diseases or a family history of systemic diseases, may affect the subject's safety or any other diseases and physiological conditions that may affect the results of the study, judged by the investigator. 13. Specific history of allergies. 14. Subjects who have used monoclonal antibodies within the 6 months prior to screening. 15. Patients who have received vaccinations within 6 weeks prior to screening. 16. Subjects who have received other antitumor therapeutic drugs for PV prior to screening. 17. Chronic diseases requiring treatment with systemic glucocorticoids or other immunosuppressants. 18. History of drug abuse or illicit drug use within 3 months prior to screening. 19. Participation in other clinical trials within 3 months prior to screening. 20. Planned elective surgery during the study. 21. History of surgery within 3 months prior to screening. 22. Intolerable iron deficiency-related symptoms judged by the investigator prior to the first dosing. 23. Pregnant or lactating females; women of reproductive age who are not using effective contraception. 24. Individuals directly associated with the research and/or their immediate family members. 25. Other factors which may potentially affect the assessment of the study results by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | Up to 141 or 197 days | Incidence of adverse events |
| Vital sign | Up to 141 or 197 days | Incidence of treatment-emergent clinically abnormal vital signs |
| Physical examination | Up to 141 or 197 days | Incidence of treatment-emergent clinically abnormal physical examinations |
| 12-lead electrocardiogram (ECG) | Up to 141 or 197 days | Incidence of treatment-emergent clinically significant 12-lead electrocardiograms (ECGs) |
| Laboratory test result | Up to 141 or 197 days | Incidence of treatment-emergent clinically significant laboratory test results |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| λz | Day 1 to Day 141 or 197 | Terminal elimination rate constant |
| t1/2z | Day 1 to Day 141 or 197 | The terminal elimination half-life |
| MRT | Day 1 to Day 141 or 197 | Mean residence time |
| Vss | Day 1 to Day 141 or 197 | Volume of Distribution at Steady State |
| CLss | Day 1 to Day 141 or 197 | Steady-state clearance |
| DF | Day 1 to Day 141 or 197 | Fluctuation percentage |
| Ctrough | Day 1 to Day 141 or 197 | Trough Concentration |
| Cmax | Day 1 to Day 141 or 197 | Plasma maximum measured drug concentration |
| Rac(cmax) | Day 1 to Day 141 or 197 | Accumulation ratio calculated from the Cmax,ss and Cmax after single dosing |
| Hepcidin | Day 1 to Day 141 or 197 | Change from baseline in hepcidin levels |
| Serum iron | Day 1 to Day 141 or 197 | Change from baseline in serum iron levels |
| Transferrin saturation (TSAT) | Day 1 to Day 141 or 197 | Change from baseline in transferrin saturation (TSAT) levels |
| Anti-drug antibodies(ADA) | Day 1 to Day 141 or 197 | The incidence of ADA |
| Hematocrit (HCT) | Day1 to Day 141 or 197 | Change from baseline in HCT levels |
| Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score（MPN-SAF TSS） | Day 1 to Day 141 or 197 | Change from baseline in MPN-SAF TSS score |
| Rac(AUC) | Day 1 to Day 141 or 197 | Accumulation ratio calculated from the AUCτ,ss and AUCτ after single dosing |
| Tmax | Day 1 to Day 141 or 197 | Time of maximum concentration |
| AUC0-τ | Day 1 to Day 141 or 197 | Area under the plasma concentration-time curve during a dosage interval（τ） |
| AUC0-t | Day 1 to Day 141 or 197 | Area under the concentration-time curve from dosing to the last measurable time point |
| AUC0-∞ | Day 1 to Day 141 or 197 | Area under the concentration-time curve from dosing to infinity |
Countries
China
Outcome results
None listed