A Multiple Ascending Dose Study of 9MW3011 in Patients With Non-transfusion-dependent β-thalassemia

A Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of 9MW3011 in Patients With Non-transfusion-dependent β- Thalassemia

This is a phase Ib, randomized, double-blind, placebo-controlled, multiple ascending dose study . The objectives of the study are to evaluate the safety , tolerability, pharmacokinetics(PK), pharmacodynamics(PD), and immunogenicity of 9MW3011 in patients with non-transfusion-dependent β- thalassemia .

Study Overview

• Status: Recruiting
• Conditions: Beta-Thalassemia
• Intervention / Treatment: Drug: 9MW3011; Drug: 9MW3011 placebo

Detailed Description

A total of 40 subjects diagnosed with non-transfusion-dependent β-thalassemia will be enrolled in this study and assigned into four dosage cohorts. In each cohort, subjects will be randomized in a 4:1 ratio to receive 9MW3011 or placebo via intravenous infusion.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yongrong Lai; Phone Number: +8607715356304; Email: laiyongrong@hotmail.com

Study Locations

• China
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Recruiting
      • The First Affiliated Hospital of Guangxi Medical University
      • Contact: Yongrong Lai; Phone Number: +8607715356304; Email: laiyongrong@hotmail.com
  • Hainan
    • Haikou, Hainan, China, 570311
      • Recruiting
      • Hainan General Hospital
      • Contact: Guyun Wang; Phone Number: +86089868642117; Email: wangguyun@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Male and female subjects aged 18 to 65 years (inclusive)
2. Subject must have a documented genetic diagnosis of β-thalassemia or hemoglobin E/ β-thalassemia
3. Subjects must meet the criteria for non-transfusion-dependent thalassemia
4. Subjects must have a baseline hemoglobin level between 70-100 g/L(inclusive), based on 2 consecutive measurements taken at least 1 week apart within 4 weeks before randomization
5. Subjects must have evidence of iron overload during screening
6. Subject must have performance status: Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
7. Subjects must fully understand the study procedures and methods, voluntarily participate in the trial, and sign an informed consent form

Key Exclusion Criteria:

1. Subjects diagnosed with alpha-thalassemia
2. Subjects diagnosed with HbS/beta-thalassemia or transfusion-dependent beta-thalassemia
3. Subjects exhibit severe iron overload at the time of screening
4. In addition to thalassemia, subjects have any other forms of anemia and hematological disorders that the investigator assesses may compromise safety or influence study outcomes
5. Combined with any significant systemic diseases or psychiatric disorders
6. Subjects have New York Heart Association (NYHA) Class III-IV heart failure and other cardiovascular diseases within 6 months prior to screening or currently present
7. During the screening or baseline period, subjects exhibiting a QTcF interval of ≥450ms for males and ≥470ms for females on a 12-lead electrocardiogram (ECG), or presenting an abnormal 12-lead ECG with clinical significance
8. Uncontrolled hypertension before screening
9. A history of malignant neoplasm occurring within the last five years
10. Severe infection requiring hospitalization or intravenous antimicrobial therapy, or uncontrolled systemic bacterial, fungal, or viral active infection
11. Subject have received concomitant treatment that was not permitted by the protocol
12. Subjects whose hematological parameters did not meet the inclusion criteria during screening
13. Subjects with a history of substance abuse, as well as those who yield positive results on substance abuse screening
14. Subjects who are unable to undergo MRI scans
15. Pregnant or lactating women
16. Subjects presenting any other factors deemed unsuitable for participation assessed by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 9MW3011 or placebo (Randomized 4:1)	Drug: 9MW3011; Ascending IV doses administered per protocol; Drug: 9MW3011 placebo; Ascending IV doses administered per protocol
Experimental: Cohort 2; 9MW3011 or placebo (Randomized 4:1)	Drug: 9MW3011; Ascending IV doses administered per protocol; Drug: 9MW3011 placebo; Ascending IV doses administered per protocol
Experimental: Cohort 3; 9MW3011 or placebo (Randomized 4:1)	Drug: 9MW3011; Ascending IV doses administered per protocol; Drug: 9MW3011 placebo; Ascending IV doses administered per protocol
Experimental: Cohort 4; 9MW3011 or placebo (Randomized 4:1)	Drug: 9MW3011; Ascending IV doses administered per protocol; Drug: 9MW3011 placebo; Ascending IV doses administered per protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event(including serious adverse event)	The incidence of Adverse Events(AEs)and Serious Adverse Events(SAEs)from treatment until the last scheduled follow-up visit	up to day 169
Number of subjects with abnormal vital signs	Vital signs measurements will include pulse rate, respiration rate, blood pressure (systolic and diastolic blood pressure) and body temperature.	up to day 169
Number of subjects with abnormal clinically significant results from physical examination	The physical examinations will include examination of the following: skin and mucous membranes, lymph nodes, head and neck, chest, abdomen, musculoskeletal, nervous system, and other sites of note elicited from the subject.	up to day 169
Number of subjects with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters	The examination indicators include heart rate, PR, QRS, uncorrected QT, and QTcF(corrected by Fridericia formula).	up to day 169
Number of subjects with abnormal clinically significant clinical laboratory results	Clinical laboratory tests include hematology, urinalysis, blood chemistry, coagulation function.	up to day 169

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of 9MW3011 in serum		up to day 169
PD-parameters-hepcidin	Change from baseline in hepcidin levels	up to day 169
PD-parameters-serum iron	Change from baseline in serum iron levels	up to day 169
Anti-drug antibody(ADA)	The incidence of ADA	up to day 169
Liver iron concentration(LIC)	Change from baseline in LIC	up to day 169

Collaborators and Investigators

• Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 9, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: 9MW3011-C04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No