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A Study of MY008211A in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
MY008211A tablets
Sponsored by
Wuhan Createrna Science and Technology Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male and female participants ≥ 18 years of age, BMI≥18 kg/m2,with a diagnosis of PNH confirmed by laboratory tests, according to the PNH diagnostic criteria in the Chinese Guidelines for the Diagnosis and Treatment of Rare Diseases (2019 edition) , and 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.

Sites / Locations

  • Nstitute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm1:low MY008211A dose

Arm2:high MY008211A dose

Arm Description

Participants will receive low MY008211A dose orally b.i.d

Participants will receive high MY008211A dose orally b.i.d

Outcomes

Primary Outcome Measures

Proportion of participants achieving a sustained increase in hemoglobin levels of ≥ 20 g/L in the absence of red blood cell transfusion.
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

Proportion of participants achieving sustained hemoglobin levels ≥ 120 g/L in the absence of red blood cell transfusions.
Proportion of participants achieving sustained hemoglobin levels ≥ 120 g/L in absence of red blood cell transfusion
Change from baseline in hemoglobin concentration.
Change from baseline in hemoglobin concentration (g/L) in absence of red blood cell transfusion
Change from baseline in serum LDH levels.
Change from baseline in serum LDH levels (U/L)
Change from baseline in Reticulocyte count.
Change from baseline in Reticulocyte count (×10^9/L)
Changes from baseline in transfusion volume.
The average number of red blood cells transfused per week
Change in the level of PNH red cell clones.
Change from baseline in the level of PNH red cell clones.
Occurrences of AEs occurring between Day 1 and Day 84.
Adverse Events (AEs)

Full Information

First Posted
September 11, 2023
Last Updated
September 17, 2023
Sponsor
Wuhan Createrna Science and Technology Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT06050226
Brief Title
A Study of MY008211A in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official Title
A Multi-center, Randomized, Open-label, Phase 2 Study to Evaluate the Efficacy and Safety of MY008211A Tablets in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria and Active Hemolysis.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2023 (Actual)
Primary Completion Date
January 30, 2024 (Anticipated)
Study Completion Date
July 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wuhan Createrna Science and Technology Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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, in China.
Detailed Description
The purpose of this study is to determine whether MY008211A is efficacious and safe for the treatment of PNH patients who are naive to complement inhibitor therapy, including anti-C5 antibody.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm1:low MY008211A dose
Arm Type
Experimental
Arm Description
Participants will receive low MY008211A dose orally b.i.d
Arm Title
Arm2:high MY008211A dose
Arm Type
Experimental
Arm Description
Participants will receive high MY008211A dose orally b.i.d
Intervention Type
Drug
Intervention Name(s)
MY008211A tablets
Other Intervention Name(s)
MY008211A
Intervention Description
The first 10 participants will be received low-dose MY008211A tablets, and the next 30 participants will be randomized to low-dose or high-dose treatment arms in a 1:2 ratio.
Primary Outcome Measure Information:
Title
Proportion of participants achieving a sustained increase in hemoglobin levels of ≥ 20 g/L in the absence of red blood cell transfusion.
Description
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
Time Frame
up to 84 days
Secondary Outcome Measure Information:
Title
Proportion of participants achieving sustained hemoglobin levels ≥ 120 g/L in the absence of red blood cell transfusions.
Description
Proportion of participants achieving sustained hemoglobin levels ≥ 120 g/L in absence of red blood cell transfusion
Time Frame
up to 84 days
Title
Change from baseline in hemoglobin concentration.
Description
Change from baseline in hemoglobin concentration (g/L) in absence of red blood cell transfusion
Time Frame
up to 84 days
Title
Change from baseline in serum LDH levels.
Description
Change from baseline in serum LDH levels (U/L)
Time Frame
up to 84 days
Title
Change from baseline in Reticulocyte count.
Description
Change from baseline in Reticulocyte count (×10^9/L)
Time Frame
up to 84 days
Title
Changes from baseline in transfusion volume.
Description
The average number of red blood cells transfused per week
Time Frame
up to 84 days
Title
Change in the level of PNH red cell clones.
Description
Change from baseline in the level of PNH red cell clones.
Time Frame
up to 84 days
Title
Occurrences of AEs occurring between Day 1 and Day 84.
Description
Adverse Events (AEs)
Time Frame
up to 84 days
Other Pre-specified Outcome Measures:
Title
Changes from baseline in alternative complement pathway activity.
Description
Alternative complement pathway activity measured by the WIESLAB® kit.
Time Frame
up to 84 days
Title
Change from baseline in plasma levels of the Bb fragment.
Description
Bb fragment cleaved by factor B of complement.
Time Frame
up to 84 days
Title
Maximum Plasma Concentration (Cmax) Of MY008211A tablets
Description
PK parameters
Time Frame
up to 84 days
Title
Area Under The Concentration Versus Time Curve (AUC) Of MY008211A
Description
PK parameters
Time Frame
up to 84 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female participants ≥ 18 years of age, BMI≥18 kg/m2,with a diagnosis of PNH confirmed by laboratory tests, according to the PNH diagnostic criteria in the Chinese Guidelines for the Diagnosis and Treatment of Rare Diseases (2019 edition) , and 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhen Fu, Ph.D
Phone
13477072640
Email
fuzhen@createrna.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yinzhen Wang, master
Phone
15570895091
Email
wangyinzhen@createrna.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fengkui Zhang, Ph.D
Organizational Affiliation
Blood Disease Hospital, Chinese Academy of Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nstitute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fengkui Zhang, PhD

12. IPD Sharing Statement

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A Study of MY008211A in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

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