Study of Safety and Efficacy of MY008211A in in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Phase 2

Not yet recruiting

• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Interventions: Drug: MY008211A tablets

• Registration Number: NCT06134414
• Lead Sponsor: Wuhan Createrna Science and Technology Co., Ltd

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.

Study Timeline

• Status Verified: 2023-10
• Study First Submitted: 2023-11-10
• Study First Submitted QC: 2023-11-10
• Last Update Submitted: 2023-11-17
• Study First Posted: 2023-11-18
• Last Update Posted: 2023-11-22
• Study Start: 2024-12
• Primary Completion: 2025-07
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1 MY008211A low dose	MY008211A tablets	Participants will receive MY008211A at a dose of 400 mg orally b.i.d
Arm 2 MY008211A high dose	MY008211A tablets	Participants will receive MY008211A at a dose of 600 mg orally b.i.d

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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 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 LDH level from baseline	Day7, 14, 21, 28, 42, 56 and 70	Change in LDH level from baseline
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.
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
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)
The proportion of patients without RBC transfusion	Day14, 21, 28, 42, 56 and 70	The proportion of patients without RBC transfusion
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 level of PNH RBC clones from baseline in patients without RBC transfusion.	Day70	Change from baseline in the level of PNH red cell clones.
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
Incidence of Adverse Events (AEs) between Day 1 and Day 70	Day 70	Adverse Events (AEs)