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

NCT04220801 | Completed Phase 1 FDA Drug

• 1 other identifier: ZM-H1505R-101
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (8)

Cohort 1 of Part 1 (SAD)

EXPERIMENTAL

300 mg ZM-H1505R or placebo

Drug: ZM-H1505R

Cohort 2 of Part 1(SAD)

EXPERIMENTAL

450 mg ZM-H1505R or placebo

Drug: ZM-H1505R

Cohort 3 of Part 1(SAD)

EXPERIMENTAL

150 mg ZM-H1505R or placebo (2 periods)

Drug: ZM-H1505R

Cohort 4 of Part 1(SAD)

EXPERIMENTAL

75 mg ZM-H1505R or placebo

Drug: ZM-H1505R

Cohort 5 of Part 1(SAD)

EXPERIMENTAL

25 mg ZM-H1505R or placebo

Drug: ZM-H1505R

Cohort 1 of Part 2 (MAD)

EXPERIMENTAL

75 mg ZM-H1505R or placebo

Drug: ZM-H1505R

Cohort 2 of Part 2 (MAD)

EXPERIMENTAL

150 mg ZM-H1505R or placebo

Drug: ZM-H1505R

Cohort 3 of Part 2 (MAD)

EXPERIMENTAL

300 mg ZM-H1505R or placebo

Drug: ZM-H1505R

Interventions

ZM-H1505R DRUG

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.

Cohort 1 of Part 1 (SAD); Cohort 1 of Part 2 (MAD); Cohort 2 of Part 1(SAD); Cohort 2 of Part 2 (MAD); Cohort 3 of Part 1(SAD); Cohort 3 of Part 2 (MAD); Cohort 4 of Part 1(SAD); Cohort 5 of Part 1(SAD)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. Are capable of giving informed consent and complying with study procedures;
• \. Are between the ages of 18 and 55 years, inclusive;
• \. Female subjects have a negative pregnancy test results at screening and Day -1, and meet one of the following criteria:
• Using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) \[e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)\]
• 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)
• 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;
• \. Considered healthy by the Investigator, based on subject's reported medical history, full PE, clinical laboratory tests, 12-lead ECG, and vital signs;
• \. 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;
• \. Non-smoker and no nicotine containing products (including e-cigarettes) within 6 months;

You may not qualify if:

• \. 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;
• \. Reported or suspected malignancy;
• \. Reported history of pancreatitis or gall stones;
• \. Reported history of unexplained syncope, symptomatic hypotension or hypoglycemia;
• \. Reported family history of long QTc syndrome;
• \. Reported history of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance;
• \. Poor venous access;
• \. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody;
• \. Donated or lost \>500ml of blood in the previous 3 months;
• \. Taken an investigational drug or participated in a clinical trial within 3 months (or 5 half-lives), whichever is longer;
• \. Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug;
• \. Hospital admission or major surgery within 6 months prior to screening;
• \. A reported history of prescription drug abuse, or illicit drug use within 9 months prior to screening;
• \. A reported history of alcohol abuse according to medical history within 9 months prior to screening;
• \. A positive screen for alcohol, drugs of abuse at screening or Day -1;

Sponsors & Collaborators

• Shanghai Zhimeng Biopharma, Inc.: lead

Study Sites (1)

Frontage Clinical Services

Secaucus, New Jersey, 07094, United States

Location

Related Publications (1)

• Jiang X, Hua B, Liu G, Xia T, Deng A, Lu H, Guo R, Wang Z, Liang B, Chen H, Jin Q, Zhang Z. Safety, Tolerability, and Pharmacokinetics of a Novel Human Hepatitis B Virus Capsid Assembly Modulator Canocapavir: A Randomized First-in-Human Study. Gastro Hep Adv. 2023 Jan 7;2(4):524-531. doi: 10.1016/j.gastha.2023.01.001. eCollection 2023.

  PMID: 39132049 DERIVED

Study Officials

• Gregory Tracey, MD.

  Frontage Clinical Services, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2019
• First Posted: January 7, 2020
• Study Start: February 17, 2020
• Primary Completion: November 18, 2020
• Study Completion: November 18, 2020
• Last Updated: April 28, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)