A Study of MY008211A in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy of MY008211A in adult patients with PNH , showing signs of active hemolysis, in China.

Detailed Description
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The purpose of this study is to determine whether MY008211A is efficacious and safe for the treatment of PNH patients who are naive to complement inhibitor therapy, including anti-C5 antibody.

Official Title
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A Multi-center, Randomized, Open-label, Phase 2 Study to Evaluate the Efficacy and Safety of MY008211A Tablets in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria and Active Hemolysis.

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Drug: MY008211A tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants ≥ 18 years of age, BMI≥18 kg/m2，with a diagnosis of PNH confirmed by laboratory tests, according to the PNH diagnostic criteria in the Chinese Guidelines for the Diagnosis and Treatment of Rare Diseases (2019 edition) , and flow cytometry with clone size ≥ 10%. Mean hemoglobin level <100 g/L. LDH > 1.5 x Upper Limit of Normal (ULN) Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment. If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given. Exclusion Criteria: Patients with reticulocytes <100x10^9/L; platelets <30x10^9/L; neutrophils <0.5x10^9/L. Were using a complement inhibitor before the first administration of MY008211A tablets or had discontinued a previous complement inhibitor for less than five half-lives or 120 days, whichever was the longest. History of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus. Known or suspected hereditary complement deficiency Previous bone marrow or hematopoietic stem cell transplantation. Previous splenectomy. A history of malignancy within 5 years before screening, except cured local basal cell carcinoma of the skin and carcinoma in situ of the cervix.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm1：low MY008211A dose<br>Participants will receive low MY008211A dose orally b.i.d | Drug: MY008211A tablets<br>* The first 10 participants will be received low-dose MY008211A tablets, and the next 30 participants will be randomized to low-dose or high-dose treatment arms in a 1:2 ratio.<br>* Other names: MY008211A;|
| Experimental: Arm2：high MY008211A dose<br>Participants will receive high MY008211A dose orally b.i.d | Drug: MY008211A tablets<br>* The first 10 participants will be received low-dose MY008211A tablets, and the next 30 participants will be randomized to low-dose or high-dose treatment arms in a 1:2 ratio.<br>* Other names: MY008211A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving a sustained increase in hemoglobin levels of ≥ 20 g/L in the absence of red blood cell transfusion. | Proportion of participants achieving a sustained increase from baseline in hemoglobin levels of ≥ 20 g/L assessed , in the absence of red blood cell transfusions | up to 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving sustained hemoglobin levels ≥ 120 g/L in the absence of red blood cell transfusions. | Proportion of participants achieving sustained hemoglobin levels ≥ 120 g/L in absence of red blood cell transfusion | up to 84 days | 
| Change from baseline in hemoglobin concentration. | Change from baseline in hemoglobin concentration (g/L) in absence of red blood cell transfusion | up to 84 days | 
| Change from baseline in serum LDH levels. | Change from baseline in serum LDH levels (U/L) | up to 84 days | 
| Change from baseline in Reticulocyte count. | Change from baseline in Reticulocyte count (×10^9/L) | up to 84 days | 
| Changes from baseline in transfusion volume. | The average number of red blood cells transfused per week | up to 84 days | 
| Change in the level of PNH red cell clones. | Change from baseline in the level of PNH red cell clones. | up to 84 days | 
| Occurrences of AEs occurring between Day 1 and Day 84. | Adverse Events (AEs) | up to 84 days |