Paroxysmal Nocturnal Hemoglobinuria (PNH)
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.
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.
Interventions
dose 1 (400 mg BID) and dose 2 (600 mg BID) in a 1:1 ratio by central randomization
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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) |
| The proportion of patients without RBC transfusion | Day14, 21, 28, 42, 56 and 70 | The proportion of patients without RBC transfusion |
Contacts
Primary ContactXiaoni Li, Ph.D
Outcome results
None listed