To Evaluate the Effect of Single Oral Dose of MY008211A Tablets on QTc Interval in Healthy Subjects

A Single-center, Randomized, Double-blind, Single Oral Dose, Placebo-controlled Study to Evaluate the Effect of MY008211A Tablets on QTc Interval in Healthy Chinese Adult Subjects

A Concentration-QT Interval Correction (C-QTc) study of MY008211A Tablets in Healthy Subjects

Study Overview

• Status: Not yet recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: MY008211A tablets; Drug: Placebo

Detailed Description

This is a single-center, randomized, double-blind, single oral dose, two groups, placebo-controlled study with 2 dose sequences preset

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuhui Hu, master; Phone Number: 86 021-51158605; Email: huyuhui@createrna.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100089
      • Peking University Third Hospital
      • Contact: Haiyan Li, PhD; Phone Number: 86 010-68966677-8509; Email: haiyanli1027@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Volunteers must be fully informed of this study and the content, process of the study and possible adverse events related to experimental drug will be fully understood, and voluntarily signed a written Informed Consent Form (ICF);
2. 18≤ age ≤ 45 years old, male or female Chinese adult volunteers;
3. Body weight: ≥50 kg for male, ≥45 kg for female; body mass index (BMI): 19.0-26.0 kg/m2 (inclusive) at screening;
4. Volunteers should be able to communicate well with the investigator, understand and comply with the requirements of the study.

Exclusion Criteria:

1. The investigator judges that there are other disease or medical conditions that are clinical significant or may prevent the volunteer from following the study protocol and completing the study, abnormal including but not limited to central nervous system, cardiovascular system, digestive system, respiratory system, urinary system, hematological system, immune system, mental system, endocrine and metabolic system;
2. Volunteers with chronic or active gastrointestinal diseases such as esophageal disease, gastritis, gastric ulcer, enteritis, active gastrointestinal bleeding, or gastrointestinal surgery within the past three years and judged by the investigator to have clinical significance at present;
3. Volunteers with torsades de pointes (TDP) or other risk factors for malignant arrhythmias, or short QT syndrome, long QT syndrome, sudden unexplained death or drowning in youth (≤ 40 years old), or a family history of a first-degree relative (i.e., biological parent, sibling, or child) of sudden infant death syndrome, or other heart disease that the investigators determined was not suitable for inclusion;
4. Volunteers with hyperkalemia, hypokalemia, hypermagnesia, hypomagnesemia, hypercalcemia or hypocalcemia and judged by the investigator to have clinical significance;
5. History of known or suspected immunodeficiency (e.g., history of frequent recurrent infections), inherited or acquired complement deficiency；
6. Volunteers who underwent surgery within 6 months pre-dose, which judged by the investigator to affect the absorption, distribution, metabolism, and excretion of the experimental drug(e.g. cholecystectomy, except appendicitis surgery); Surgical procedures within 4 weeks pre-dose or planned to undergo a surgical procedure during the trial;
7. Volunteers who had a clear history of capsular microbial infection within 6 months before screening; Including but not limited to: Streptococcus pneumoniae, Bacillus anthracis, Salmonella, Salmonella typhi, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, Neisseria meningitidis, Haemophilus influenzae, Legionella pneumophila infection history;
8. Volunteers with previous or current history of TB infection or with positive lymphobacteria culture + interferon test；
9. Active systemic bacterial, viral, or fungal infection within 14 days pre-dose;
10. Fever (≥ 38 ℃) within 7 days pre-dose;
11. Volunteers with a history of clinically significant drug allergy or allergic disease (such as asthma, urticaria, eczematous dermatitis, etc.), or a possible or clear allergy to the experimental drug (including similar drugs) or any excipients thereof as judged by the investigator;
12. Volunteers with clinical significant examination abnormalities which judged by the investigator such as vital signs, physical examination, routine laboratory tests (can reviewable, including: blood routine, reticulocyte count, procalcitonin + myoglobin, blood biochemical + hypersensitive C-reactive protein, urine routine, coagulation function + plasma D-Dimer determination), chest X-ray, abdominal ultrasound at screening or baseline；
13. Volunteers with 12-ECG examination and reviewable result such as QTcF≥450 ms or PR interval ≥200ms or QRS wave complex ≥120ms or clinical significant abnormality ECG which judged by the investigator at screening or baseline or pre-dose；
14. Volunteers who administrated any other clinical study drug or enrolled in any Interventional clinical trial within 3 months before screening；
15. Volunteers who donated blood or lost blood (≥ 400mL) within 3 months pre-dose, received a blood transfusion or use of blood products within 4 weeks pre-dose, or intended to donate blood or blood components during or within 3 months after study;
16. Volunteers who had taken any medicine or OTC medicine or Chinese herbal medicine or food supplement (including vitamins, health foods, etc.) other non-drug therapeutic factors that affect drug absorption, distribution, metabolism and excretion;
17. Volunteers who received a vaccine or live attenuated vaccine within 14 days pre-dose, or who plan to receive a vaccine during the study;
18. Volunteers with difficulty in blood collection or cannot tolerate intravenous puncture;
19. Volunteers with a history of drug use or substance abuse or with positive urine drug abuse screening test;
20. Volunteers with any positive result of virological test;
21. Volunteers who drink more than 14 units a week (one unit is defined as 360mL of beer or 45mL of liquor or 150mL of wine) within 3 months before screening or with positive result of alcohol breath test or unwillingness to stop drinking alcohol or any alcohol-based product during the study；
22. Volunteers who smoke more than 5 cigarettes per day(or use a significant amount of nicotine products) within 3 months before screening or will be unable to stop using any tobacco products during the study or with positive result of urine nicotine test；
23. Volunteers who habitual consumption of grapefruit juice or excessive amounts of tea, coffee and/or caffeinated beverages and will be unable to stop use during the study, or consume any food or drink containing chocolate, caffeine, or rich in xanthines within 48h pre-dose；
24. Volunteers who have special requirements for diet and cannot abide by the uniform diet；
25. Volunteers (or their partners) who plan to be pregnant or donate sperm or eggs during the study to 3 months after the end of the study, or who are unwilling to take one or more non-drug contraceptive measures (such as complete abstinence, condoms, contraceptive rings, surgical sterilization, etc.);
26. Volunteers of pregnant or lactating women; or having unprotected sex within 2 weeks pre-dose; or oral contraceptive use within 30 days or long-acting estrogen or progestin injectable or implant use within 6 months pre-dose; or with positive blood pregnancy test pre-dose;
27. Volunteers have other reasons for not fit for participating in the study as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A, Sequence 1, Dose 1; Participants randomized to receive MY008211A tablets or placebo on Day 1.	Drug: MY008211A tablets; Subjects of Group A receive MY008211A tablets on Day 1 of both Sequence, wash-out period is 6 Days at least.
Experimental: Group A, Sequence 2, Dose 2; Participants randomized to receive MY008211A tablets or placebo on Day 7.	Drug: MY008211A tablets; Subjects of Group A receive MY008211A tablets on Day 1 of both Sequence, wash-out period is 6 Days at least.
Placebo Comparator: Group B, Sequence 1, Dose 1; Participants randomized to receive MY008211A tablets or placebo on Day 1.	Drug: Placebo; Subjects of Group A receive placebo tablets on Day 1 of both Sequence, wash-out period is 6 Days at least.
Placebo Comparator: Group B, Sequence 2, Dose 2; Participants randomized to receive MY008211A tablets or placebo on Day 7.	Drug: Placebo; Subjects of Group A receive placebo tablets on Day 1 of both Sequence, wash-out period is 6 Days at least.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ΔΔQTcF (Using Fridericia Formula as the Primary Method for QT Interval Correction)	Placebo-corrected, baseline-adjusted QTc interval of prodrug and active metabolite (if necessary)	up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (Maximum plasma concentration)	Cmax of prodrug and active metabolite (if necessary)	up to 2 weeks
Tmax (Time to maximum plasma concentration)	Tmax of prodrug and active metabolite (if necessary)	up to 2 weeks
t1/2 (Terminal elimination half-life time)	t1/2 of prodrug and active metabolite (if necessary)	up to 2 weeks
AUC0-t (Area under the plasma concentration-time curve from time 0 to the collection time t with the last measurable plasma concentration)	AUC0-t of prodrug and active metabolite (if necessary)	up to 2 weeks
AUC0-∞ (Area under the plasma concentration-time curve extrapolated from time 0 to infinity)	AUC0-∞ of prodrug and active metabolite (if necessary)	up to 2 weeks
CL/F (Apparent clearance)	CL/F of prodrug and active metabolite (if necessary)	up to 2 weeks
Vz/F (Apparent volume of distribution)	Vz/F of prodrug and active metabolite (if necessary)	up to 2 weeks
The incidence and severity of adverse events to assess safety and tolerability	such as laboratory abnormalities	up to 3 weeks
Other Electrocardiogram (ECG) parameters	Such as T-wave morphology or absence, U-wave presence and absence, HR, RR interval, PR interval, QRS wave complex	up to 2 weeks

Collaborators and Investigators

• Sponsor: Wuhan Createrna Science and Technology Co., Ltd
• Investigators: Principal Investigator: Haiyan Li, PhD, PI

Study record dates

Study Major Dates

• Study Start (Estimated): August 10, 2024
• Primary Completion (Estimated): September 27, 2024
• Study Completion (Estimated): December 13, 2024

Study Registration Dates

• First Submitted: August 2, 2024
• First Submitted That Met QC Criteria: August 6, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: MY008211-1-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Trade secrets

Drug and device information, study documents

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