Study of Safety and Efficacy of MY008211A in in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1 MY008211A low dose Participants will receive MY008211A at a dose of 400 mg orally b.i.d |
Drug: MY008211A tablets
dose 1 (400 mg BID) and dose 2 (600 mg BID) in a 1:1 ratio by central randomization
Other Names:
|
| Experimental: Arm 2 MY008211A high dose Participants will receive MY008211A at a dose of 600 mg orally b.i.d |
Drug: MY008211A tablets
dose 1 (400 mg BID) and dose 2 (600 mg BID) in a 1:1 ratio by central randomization
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 [Day 70]
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 Outcome Measures
- 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 an increase in hemoglobin ≥ 20 g/L from baseline 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]
The proportion of patients with hemoglobin ≥ 120 g/L among those without RBC transfusion
- Change in hemoglobin concentration from baseline in patients without RBC transfusion [Day14, 21, 28, 42, 56 and 70]
Change in hemoglobin concentration from baseline in patients without RBC transfusion
- Change in LDH level from baseline [Day7, 14, 21, 28, 42, 56 and 70]
Change in LDH level from baseline
- The proportion of patients with hemolysis controlled [Day7, 14, 21, 28, 42, 56 and 70]
The proportion of patients with hemolysis controlled (defined as LDH < 1.5 ULN)
- Change in reticulocyte count from baseline in patients without RBC transfusion [Day7, 14, 21, 28, 42, 56 and 70]
Change in reticulocyte count from baseline in patients without RBC transfusion
- Change in indirect bilirubin level from baseline [Day7, 14, 21, 28, 42, 56 and 70]
Change in indirect bilirubin level from baseline
- The proportion of patients without RBC transfusion [Day14, 21, 28, 42, 56 and 70]
The proportion of patients without RBC transfusion
- Change in the average weekly amount of RBC transfused during the efficacy observation period [Day70]
Change in the average weekly amount of RBC transfused during the efficacy observation period compared with that pre-dose
- Change From Baseline in FACIT-Fatigue Questionnaire [Day7, 14, 21, 28, 42, 56 and 70]
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.
- Changes from baseline in alternative complement pathway activity [Day14, 28, 56 and 70]
Alternative complement pathway activity measured by the WIESLAB® kit.
- Change in the amount of fragment Bb of CFB in plasma from baseline [Day14, 28, 56 and 70]
Bb fragment cleaved by factor B of complement.
- Change in the level of PNH RBC clones from baseline in patients without RBC transfusion. [Day70]
Change from baseline in the level of PNH red cell clones.
- Incidence of Adverse Events (AEs) between Day 1 and Day 70 [Day 70]
Adverse Events (AEs)
Eligibility Criteria
Criteria
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 <100x109/L; platelets <30x109/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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Wuhan Createrna Science and Technology Co., Ltd
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MY008211A-PNH-2-01-F