Study of Safety and Efficacy of MY008211A in in 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.

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 naïve to complement inhibitor therapy, including anti-C5 antibody.

Official Title
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A Multi-center, Randomized, Parallel, Open-label Clinical Phase II Study, to Evaluate the Efficacy and Safety of MY008211A in Adult Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients With Signs of Active Hemolysis

Conditions
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Paroxysmal Nocturnal Hemoglobinuria (PNH)

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 and BMI ≥ 18.0 kg/m2 with a diagnosis of PNH confirmed by high-sensitivity 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: Arm 1 MY008211A low dose<br>Participants will receive MY008211A at a dose of 400 mg orally b.i.d | Drug: MY008211A tablets<br>* dose 1 (400 mg BID) and dose 2 (600 mg BID) in a 1:1 ratio by central randomization<br>* Other names: MY008211A;|
| Experimental: Arm 2 MY008211A high dose<br>Participants will receive MY008211A at a dose of 600 mg orally b.i.d | Drug: MY008211A tablets<br>* dose 1 (400 mg BID) and dose 2 (600 mg BID) in a 1:1 ratio by central randomization<br>* Other names: MY008211A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with an increase in hemoglobin concentration ≥ 20 g/L from baseline among subjects who do not receive RBC transfusion after 4 weeks of dosing | 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 | Day 70 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with an increase in hemoglobin ≥ 20 g/L from baseline among those without RBC transfusion | The proportion of patients with an increase in hemoglobin ≥ 20 g/L from baseline among those without RBC transfusion | Day14, 21, 28, 42, 56 | 
| The proportion of patients with hemoglobin ≥ 120 g/L among those without RBC transfusion | The proportion of patients with hemoglobin ≥ 120 g/L among those without RBC transfusion | Day14, 21, 28, 42, 56 and 70 | 
| Change in hemoglobin concentration from baseline in patients without RBC transfusion | Change in hemoglobin concentration from baseline in patients without RBC transfusion | Day14, 21, 28, 42, 56 and 70 | 
| Change in LDH level from baseline | Change in LDH level from baseline | Day7, 14, 21, 28, 42, 56 and 70 | 
| The proportion of patients with hemolysis controlled | The proportion of patients with hemolysis controlled (defined as LDH < 1.5 ULN) | Day7, 14, 21, 28, 42, 56 and 70 | 
| Change in reticulocyte count from baseline in patients without RBC transfusion | Change in reticulocyte count from baseline in patients without RBC transfusion | Day7, 14, 21, 28, 42, 56 and 70 | 
| Change in indirect bilirubin level from baseline | Change in indirect bilirubin level from baseline | Day7, 14, 21, 28, 42, 56 and 70 | 
| The proportion of patients without RBC transfusion | The proportion of patients without RBC transfusion | Day14, 21, 28, 42, 56 and 70 | 
| Change in the average weekly amount of RBC transfused during the efficacy observation period | Change in the average weekly amount of RBC transfused during the efficacy observation period compared with that pre-dose | Day70 | 
| Change From Baseline in FACIT-Fatigue Questionnaire | Change from baseline in FACIT-Fatigue scores. The FACIT-Fatigue is a 13-item questionnaire with support for its validity and reliability in PNH that assesses patient self-reported fatigue and its impact on daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-F Scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best. | Day7, 14, 21, 28, 42, 56 and 70 | 
| Changes from baseline in alternative complement pathway activity | Alternative complement pathway activity measured by the WIESLAB® kit. | Day14, 28, 56 and 70 | 
| Change in the amount of fragment Bb of CFB in plasma from baseline | Bb fragment cleaved by factor B of complement. | Day14, 28, 56 and 70 | 
| Change in the level of PNH RBC clones from baseline in patients without RBC transfusion. | Change from baseline in the level of PNH red cell clones. | Day70 | 
| Incidence of Adverse Events (AEs) between Day 1 and Day 70 | Adverse Events (AEs) | Day 70 |