Beta-Thalassemia
Conditions
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.
Interventions
DRUG9MW3011
Ascending IV doses administered per protocol
DRUG9MW3011 placebo
Ascending IV doses administered per protocol
Sponsors
Mabwell (Shanghai) Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with abnormal clinically significant clinical laboratory results | up to day 169 | Clinical laboratory tests include hematology, urinalysis, blood chemistry, coagulation function. |
| Adverse Event(including serious adverse event) | up to day 169 | The incidence of Adverse Events(AEs)and Serious Adverse Events(SAEs)from treatment until the last scheduled follow-up visit |
| Number of subjects with abnormal vital signs | up to day 169 | Vital signs measurements will include pulse rate, respiration rate, blood pressure (systolic and diastolic blood pressure) and body temperature. |
| Number of subjects with abnormal clinically significant results from physical examination | up to day 169 | 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. |
| Number of subjects with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters | up to day 169 | The examination indicators include heart rate, PR, QRS, uncorrected QT, and QTcF(corrected by Fridericia formula). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of 9MW3011 in serum | up to day 169 | — |
| PD-parameters-hepcidin | up to day 169 | Change from baseline in hepcidin levels |
| Liver iron concentration(LIC) | up to day 169 | Change from baseline in LIC |
| PD-parameters-serum iron | up to day 169 | Change from baseline in serum iron levels |
| Anti-drug antibody(ADA) | up to day 169 | The incidence of ADA |
Countries
China
Contacts
Primary ContactYongrong Lai
Outcome results
None listed