Paroxysmal Nocturnal Hemoglobinuria
Conditions
Brief summary
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
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.
Interventions
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.
Sponsors
Wuhan Createrna Science and Technology Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving a sustained increase in hemoglobin levels of ≥ 20 g/L in the absence of red blood cell transfusion. | up to 84 days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in serum LDH levels. | up to 84 days | Change from baseline in serum LDH levels (U/L) |
| Change from baseline in Reticulocyte count. | up to 84 days | Change from baseline in Reticulocyte count (×10\^9/L) |
| Changes from baseline in transfusion volume. | up to 84 days | The average number of red blood cells transfused per week |
| Change in the level of PNH red cell clones. | up to 84 days | Change from baseline in the level of PNH red cell clones. |
| Occurrences of AEs occurring between Day 1 and Day 84. | up to 84 days | Adverse Events (AEs) |
| Proportion of participants achieving sustained hemoglobin levels ≥ 120 g/L in the absence of red blood cell transfusions. | up to 84 days | Proportion of participants achieving sustained hemoglobin levels ≥ 120 g/L in absence of red blood cell transfusion |
| Change from baseline in hemoglobin concentration. | up to 84 days | Change from baseline in hemoglobin concentration (g/L) in absence of red blood cell transfusion |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) Of MY008211A tablets | up to 84 days | PK parameters |
| Area Under The Concentration Versus Time Curve (AUC) Of MY008211A | up to 84 days | PK parameters |
| Changes from baseline in alternative complement pathway activity. | up to 84 days | Alternative complement pathway activity measured by the WIESLAB® kit. |
| Change from baseline in plasma levels of the Bb fragment. | up to 84 days | Bb fragment cleaved by factor B of complement. |
Countries
China
Outcome results
None listed