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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Intervention / Treatment: Drug: MY008211A tablets

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 Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoni Li, Ph.D; Phone Number: 021-51158605; Email: lixiaoni@createrna.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: MY008211A
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: MY008211A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Wuhan Createrna Science and Technology Co., Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): July 29, 2025
• Last Update Submitted That Met QC Criteria: July 27, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Urological Manifestations; Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Proteinuria; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: MY008211A-PNH-2-01-F

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No