A Study of Orally Administered ZM-H1505R to Evaluate Safety, Tolerability and Pharmacokinetics After Single and Multiple Ascending Doses in Healthy Participants

A Randomized, Double-blind, Placebo-controlled, Sequential Single and Multiple Ascending Dose (SAD/MAD) Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of ZM-H1505R

ZM-H1505R is an investigational drug developed by Shanghai Zhimeng Biopharma Inc. for the treatment of Chronic Hepatitis B.

The purpose of this study is to see how safe the study drug is and how well it is tolerated after dosing. The study will also test how the study drug is taken up and eliminated by the body. An additional part of the study is to look at how this could be changed by giving the study drug with food.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: ZM-H1505R

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Secaucus, New Jersey, United States, 07094
      • Frontage Clinical Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Are capable of giving informed consent and complying with study procedures;
• 2. Are between the ages of 18 and 55 years, inclusive;

• 3. Female subjects have a negative pregnancy test results at screening and Day -1, and meet one of the following criteria:

  1. Using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)]

  2. Surgically sterile for at least 3 months prior to screening by one of the following means:

     • Bilateral tubal ligation
     • Bilateral salpingectomy (with or without oophorectomy)
     • Surgical hysterectomy
     • Bilateral oophorectomy (with or without hysterectomy)

  3. Postmenopausal, defined as the following:

     • Last menstrual period greater than 12 months prior to screening
     • Postmenopausal status confirmed by serum FSH and estradiol levels at screening;
• 4. Considered healthy by the Investigator, based on subject's reported medical history, full PE, clinical laboratory tests, 12-lead ECG, and vital signs;
• 5. Normal liver function (AST/ALT < 1.5x ULN) and normal renal function (eGFR> 60mL/min/1.73 m2) as determined by Investigator following review of clinical laboratory test results;

• 6. Non-smoker and no nicotine containing products (including e-cigarettes) within 6 months;

  -- 7. Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive and body weight not less than 50 kg;

• 8. Willing and able to adhere to study restrictions and to be confined at the clinical research center.
• 9. Male subjects with female partners of child bearing potential must agree to use condoms for the duration of the study and until 12 weeks after dosing with the study drug and must refrain from donating sperm for this same period.

Exclusion Criteria:

• 1. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator;
• 2. Reported or suspected malignancy;
• 3. Reported history of pancreatitis or gall stones;
• 4. Reported history of unexplained syncope, symptomatic hypotension or hypoglycemia;
• 5. Reported family history of long QTc syndrome;
• 6. Reported history of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance;
• 7. Poor venous access;
• 8. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody;
• 9. Donated or lost >500ml of blood in the previous 3 months;
• 10. Taken an investigational drug or participated in a clinical trial within 3 months (or 5 half-lives), whichever is longer;
• 11. Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug;
• 12. Hospital admission or major surgery within 6 months prior to screening;
• 13. A reported history of prescription drug abuse, or illicit drug use within 9 months prior to screening;
• 14. A reported history of alcohol abuse according to medical history within 9 months prior to screening;
• 15. A positive screen for alcohol, drugs of abuse at screening or Day -1;
• 16. An unwillingness or inability to comply with food and beverage restrictions during study participation;
• 17. Use of over-the-counter (OTC) medication within 7 days, and herbal supplements (including St John's Wort, herbal teas, garlic extracts) within 7 days prior to dosing (Note: Use of acetaminophen at < 2 g/day is permitted until 24 hours prior to dosing)
• 18. Any condition or finding that in the Investigators opinion would put the subject or study conduct at risk if the subject were to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 of Part 1 (SAD); 300 mg ZM-H1505R or placebo	Drug: ZM-H1505R; Single oral doses of 300, 450, 600, 750, and 900 mg of ZM-H1505R or placebo and multiple oral doses of 450, 600, and 750 mg of ZM-H1505R or placebo will be administered in a fasted state, or in the case of Cohort 3 (Part 1), a second dose of 600 mg will be administered in the fed state. During each SAD and MAD dosing period, 2 subjects in each cohort will receive placebo instead of ZM-H1505R. The dose levels may be adjusted based on the safety and tolerability obtained from the previous cohort.
Experimental: Cohort 2 of Part 1(SAD); 450 mg ZM-H1505R or placebo	Drug: ZM-H1505R; Single oral doses of 300, 450, 600, 750, and 900 mg of ZM-H1505R or placebo and multiple oral doses of 450, 600, and 750 mg of ZM-H1505R or placebo will be administered in a fasted state, or in the case of Cohort 3 (Part 1), a second dose of 600 mg will be administered in the fed state. During each SAD and MAD dosing period, 2 subjects in each cohort will receive placebo instead of ZM-H1505R. The dose levels may be adjusted based on the safety and tolerability obtained from the previous cohort.
Experimental: Cohort 3 of Part 1(SAD); 150 mg ZM-H1505R or placebo (2 periods)	Drug: ZM-H1505R; Single oral doses of 300, 450, 600, 750, and 900 mg of ZM-H1505R or placebo and multiple oral doses of 450, 600, and 750 mg of ZM-H1505R or placebo will be administered in a fasted state, or in the case of Cohort 3 (Part 1), a second dose of 600 mg will be administered in the fed state. During each SAD and MAD dosing period, 2 subjects in each cohort will receive placebo instead of ZM-H1505R. The dose levels may be adjusted based on the safety and tolerability obtained from the previous cohort.
Experimental: Cohort 4 of Part 1(SAD); 75 mg ZM-H1505R or placebo	Drug: ZM-H1505R; Single oral doses of 300, 450, 600, 750, and 900 mg of ZM-H1505R or placebo and multiple oral doses of 450, 600, and 750 mg of ZM-H1505R or placebo will be administered in a fasted state, or in the case of Cohort 3 (Part 1), a second dose of 600 mg will be administered in the fed state. During each SAD and MAD dosing period, 2 subjects in each cohort will receive placebo instead of ZM-H1505R. The dose levels may be adjusted based on the safety and tolerability obtained from the previous cohort.
Experimental: Cohort 5 of Part 1(SAD); 25 mg ZM-H1505R or placebo	Drug: ZM-H1505R; Single oral doses of 300, 450, 600, 750, and 900 mg of ZM-H1505R or placebo and multiple oral doses of 450, 600, and 750 mg of ZM-H1505R or placebo will be administered in a fasted state, or in the case of Cohort 3 (Part 1), a second dose of 600 mg will be administered in the fed state. During each SAD and MAD dosing period, 2 subjects in each cohort will receive placebo instead of ZM-H1505R. The dose levels may be adjusted based on the safety and tolerability obtained from the previous cohort.
Experimental: Cohort 1 of Part 2 (MAD); 75 mg ZM-H1505R or placebo	Drug: ZM-H1505R; Single oral doses of 300, 450, 600, 750, and 900 mg of ZM-H1505R or placebo and multiple oral doses of 450, 600, and 750 mg of ZM-H1505R or placebo will be administered in a fasted state, or in the case of Cohort 3 (Part 1), a second dose of 600 mg will be administered in the fed state. During each SAD and MAD dosing period, 2 subjects in each cohort will receive placebo instead of ZM-H1505R. The dose levels may be adjusted based on the safety and tolerability obtained from the previous cohort.
Experimental: Cohort 2 of Part 2 (MAD); 150 mg ZM-H1505R or placebo	Drug: ZM-H1505R; Single oral doses of 300, 450, 600, 750, and 900 mg of ZM-H1505R or placebo and multiple oral doses of 450, 600, and 750 mg of ZM-H1505R or placebo will be administered in a fasted state, or in the case of Cohort 3 (Part 1), a second dose of 600 mg will be administered in the fed state. During each SAD and MAD dosing period, 2 subjects in each cohort will receive placebo instead of ZM-H1505R. The dose levels may be adjusted based on the safety and tolerability obtained from the previous cohort.
Experimental: Cohort 3 of Part 2 (MAD); 300 mg ZM-H1505R or placebo	Drug: ZM-H1505R; Single oral doses of 300, 450, 600, 750, and 900 mg of ZM-H1505R or placebo and multiple oral doses of 450, 600, and 750 mg of ZM-H1505R or placebo will be administered in a fasted state, or in the case of Cohort 3 (Part 1), a second dose of 600 mg will be administered in the fed state. During each SAD and MAD dosing period, 2 subjects in each cohort will receive placebo instead of ZM-H1505R. The dose levels may be adjusted based on the safety and tolerability obtained from the previous cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events	Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs	22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2
Number of Participants With Abnormal Physical Examinations	Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs and changes in subject PE findings	22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2
Number of Participants With Abnormal Vital Signs	Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs and changes in subject vital signs	22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2
Number of Participants With Clinically Significant Laboratory Findings	Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs and changes in subject clinical laboratory results	22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2
Number of Participants With Abnormal ECGs	Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs and changes in subject ECGs.	22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2

Collaborators and Investigators

• Sponsor: Shanghai Zhimeng Biopharma, Inc.
• Investigators: Principal Investigator: Gregory Tracey, MD., Frontage Clinical Services, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2020
• Primary Completion (Actual): November 18, 2020
• Study Completion (Actual): November 18, 2020

Study Registration Dates

• First Submitted: December 23, 2019
• First Submitted That Met QC Criteria: January 6, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: ZM-H1505R-101

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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