A Study of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of 9MW3011 in Patients With Polycythemia Vera

Official title

A Phase Ib, Multicenter, Randomized, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of 9MW3011 in Patients With Polycythemia Vera

Overview

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

• Drug 9MW3011
  Multiple dose

Primary outcome measures

• Adverse Event [Time frame: Up to 141 or 197 days]
• Vital sign [Time frame: Up to 141 or 197 days]
• Physical examination [Time frame: Up to 141 or 197 days]
• 12-lead electrocardiogram (ECG) [Time frame: Up to 141 or 197 days]
• Laboratory test result [Time frame: Up to 141 or 197 days]

Secondary outcome measures (12)

• Cmax [Time frame: Day 1 to Day 141 or 197]
• Tmax [Time frame: Day 1 to Day 141 or 197]
• AUC0-τ [Time frame: Day 1 to Day 141 or 197]
• AUC0-t [Time frame: Day 1 to Day 141 or 197]
• AUC0-∞ [Time frame: Day 1 to Day 141 or 197]
• λz [Time frame: Day 1 to Day 141 or 197]
• t1/2z [Time frame: Day 1 to Day 141 or 197]
• MRT [Time frame: Day 1 to Day 141 or 197]
• Vss [Time frame: Day 1 to Day 141 or 197]
• CLss [Time frame: Day 1 to Day 141 or 197]
• DF [Time frame: Day 1 to Day 141 or 197]
• Ctrough [Time frame: Day 1 to Day 141 or 197]

Eligibility criteria

Inclusion criteria

• Male and female patients aged 18 years or older at the time of screening.
• 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.
• Have a treatment history for PV with resistance or intolerance to hydroxyurea or Interferon alpha.
• Subjects receiving hydroxyurea, Interferon alpha, or ruxolitinib must complete a washout period before administration of the investigational drug.
• Must agree to adhere to appropriate contraception requirements during the study period.
• All female subjects with fertility capacity tested negative for blood pregnancy.
• Voluntarily participate in clinical trials and agrees to participate in the study by giving written informed consent.

Exclusion criteria

• The spleen is palpable at least 5 centimeters below the left costal margin upon palpation at baseline.
• Heart failure, unstable angina pectoris, myocardial infarction, and other thrombotic diseases within the 6 months prior to screening.
• Abnormal QTc interval of electrocardiogram within the 6 months prior to screening.
• Uncontrolled hypertension prior to screening.
• Any non-PV myeloproliferative neoplasms (MPN).
• Blast cells and blast granulocytes in the peripheral blood within the 3 months prior to screening.
• Hematological indicators do not meet the requirements at the time of screening.
• Known positive for active hepatitis B, hepatitis C, syphilis or human immunodeficiency virus (HIV) infection.
• History of invasive malignancies within the last 5 years.
• Severe infection or uncontrolled active infection.
• Other hematological and lymphatic system diseases or any diseases causing hemolysis or erythrocyte instability.
• 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.
• Specific history of allergies.
• Subjects who have used monoclonal antibodies within the 6 months prior to screening.
• Patients who have received vaccinations within 6 weeks prior to screening.
• Subjects who have received other antitumor therapeutic drugs for PV prior to screening.
• Chronic diseases requiring treatment with systemic glucocorticoids or other immunosuppressants.
• History of drug abuse or illicit drug use within 3 months prior to screening.
• Participation in other clinical trials within 3 months prior to screening.
• Planned elective surgery during the study.
• History of surgery within 3 months prior to screening.
• Intolerable iron deficiency-related symptoms judged by the investigator prior to the first dosing.
• Pregnant or lactating females; women of reproductive age who are not using effective contraception.
• Individuals directly associated with the research and/or their immediate family members.
• Other factors which may potentially affect the assessment of the study results by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 6 centers

• Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital — Zhengzhou
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• The First Affiliated Hospital of Nanchang University — Nanchang
• Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and — Tianjin
• The Second Hospital of Tianjin Medical University — Tianjin
• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT06752746 · 9MW3011-C03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗