Clinical trial NCT06772766: A Multiple Ascending Dose Study of 9MW3011 in Patients With Non-transfusion-dependent β-thalassemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Beta-Thalassemia
Lead sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-01-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 .

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Event(including serious adverse event)
timeFrame: up to day 169
measure: Number of subjects with abnormal vital signs
timeFrame: up to day 169
measure: Number of subjects with abnormal clinically significant results from physical examination
timeFrame: up to day 169
measure: Number of subjects with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters
timeFrame: up to day 169
measure: Number of subjects with abnormal clinically significant clinical laboratory results
timeFrame: up to day 169
Secondary outcomes:
measure: Concentration of 9MW3011 in serum
timeFrame: up to day 169
measure: PD-parameters-hepcidin
timeFrame: up to day 169
measure: PD-parameters-serum iron
timeFrame: up to day 169
measure: Anti-drug antibody(ADA)
timeFrame: up to day 169
measure: Liver iron concentration(LIC)
timeFrame: up to day 169
Other outcomes:
Locations:
city: Nanning
country: China
facility: The first Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
Study officials:
References: