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

Paroxysmal Nocturnal Hemoglobinuria (PNH) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06134414
• Other study ID #: MY008211A-PNH-2-01-F
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 2024
• Est. completion date: December 2025

Study information

• Verified date: October 2023
• Source: Wuhan Createrna Science and Technology Co., Ltd
• Contact: Xiaoni Li, Ph.D
• Phone: 021-51158605
• Email: lixiaoni[@]createrna.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the efficacy of MY008211A in adult patients with PNH, showing signs of active hemolysis.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention

Drug:
• MY008211A tablets
dose 1 (400 mg BID) and dose 2 (600 mg BID) in a 1:1 ratio by central randomization

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Createrna Science and Technology Co., Ltd

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Change in LDH level from baseline	Change in LDH level from baseline	Day7, 14, 21, 28, 42, 56 and 70
Secondary	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
Secondary	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
Secondary	Change in indirect bilirubin level from baseline	Change in indirect bilirubin level from baseline	Day7, 14, 21, 28, 42, 56 and 70
Secondary	The proportion of patients without RBC transfusion	The proportion of patients without RBC transfusion	Day14, 21, 28, 42, 56 and 70
Secondary	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
Secondary	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
Secondary	Changes from baseline in alternative complement pathway activity	Alternative complement pathway activity measured by the WIESLAB® kit.	Day14, 28, 56 and 70
Secondary	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
Secondary	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
Secondary	Incidence of Adverse Events (AEs) between Day 1 and Day 70	Adverse Events (AEs)	Day 70