Intravenous ZMA001 in healthy adults

A Phase 1 Single-Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Intravenous ZMA001 in Healthy Subjects

This trial will test a single IV dose of ZMA001, a monoclonal antibody, in healthy adults aged 18–60 to see if it is safe and how the body processes it.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05967299 on ClinicalTrials.gov

What this trial studies

This first-in-human, single-ascending-dose study gives one intravenous infusion of ZMA001 to healthy adults to measure safety, tolerability, and pharmacokinetics. Participants will be screened, admitted for a single inpatient visit up to 48 hours for dosing, and have blood tests, ECGs, and serial PK sampling with follow-up visits through day 113. Dose levels include 0.25, 0.5, 1.0 and 1.5 mg/kg with a placebo cohort at the highest dose. Researchers will record treatment-emergent adverse events and determine PK parameters such as Cmax, Tmax, AUC, and elimination half-life.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 18–60 without significant medical conditions who can comply with an inpatient visit and long-term follow-up through day 113.

Not a fit: People with active PAH or other serious illnesses are unlikely to receive clinical benefit from this single-dose healthy-volunteer study because it does not test efficacy in patients with disease.

Why it matters

Potential benefit: If later trials are successful, ZMA001 could reduce pulmonary vascular remodeling and lower pulmonary artery pressure, potentially providing a new treatment option for people with PAH.

How similar studies have performed: This is a first-in-human trial; monoclonal antibody approaches have shown efficacy in PAH animal models but clinical proof of concept in humans remains limited.

Eligibility criteria

* INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Stated willingness to comply with all study procedures and availability for the duration of the study
2. Male\* or female, aged 18 to 60 years, inclusive
3. In good general health as evidenced by medical history
4. Females of childbearing potential agree to use an accepted method of contraception (see below) throughout study participation and for 120 days after study drug infusion.
5. Males sexually active with a female partner must agree to use a condom with spermicide for 120 days after study drug infusion or be surgically sterile for at least 90 days before screening. Males must also agree to not donate sperm for 120 days after study drug administration.
6. Agreement to adhere to Lifestyle Considerations throughout study duration
7. Ability of subject to understand and the willingness to sign a written informed consent document.

   * Enrollment of healthy male subjects will be limited to no more than 14 out of the total study cohort of 32 in order to ensure an adequate representation of female subjects.

Accepted methods of contraception for females of childbearing potential:

* Use of an implanted or intrauterine hormonal device for at least 30 consecutive days before study drug infusion
* Use of oral, patch or injectable contraceptives or a vaginal hormonal device for at least 30 consecutive days before study drug infusion
* Use of a non-hormonal intrauterine device for at least 30 consecutive days before study drug infusion
* Two barrier methods such as a diaphragm with spermicide or a condom with spermicide

EXCLUSION CRITERIA:

An individual who meets any of the following criteria prior to informed consent will be excluded from participation in this study:

1. Pregnancy or lactation. Females of childbearing potential must have a negative serum Beta-human chorionic gonadotropin test no more than 48 hours from study drug infusion.
2. A history of human immunodeficiency virus (HIV) infection.
3. History of severe drug or excipient allergy or hypersensitivity
4. Known allergy to any of the components of the investigational drug or placebo
5. Recent infection or febrile illness within the past 14 days
6. Treatment with another investigational drug within the past 30 days or 5 half-lives, whichever is longer
7. Any vaccination within the past 4 weeks or receipt of a live-attenuated vaccine within the past 6 months
8. Use of tobacco products within the past 3 months
9. Illicit drug use (e.g. cocaine, opioids, methamphetamine, PCP) within the past 6 months or positive urine drug screen at Screening Visit
10. Marijuana (cannabis) use within the past 30 days or positive urine drug screen at Screening Visit
11. History of alcohol abuse within the past 2 years
12. Current clinically significant medical illness that is uncontrolled despite appropriate medical treatment including (but not limited to) hematologic, oncologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, infectious, hepatic, dermatologic, psychiatric, neurologic, autoimmune or allergic disease
13. Body mass index less than 17 or greater than 32 kg/m\^2
14. Clinically significant abnormal results on clinical blood testing completed at the Screening Visit
15. Electrocardiographic evidence of clinically relevant heart disease
16. Diabetes mellitus requiring medical treatment
17. Received another monoclonal antibody in the past 30 days
18. Use of herbal supplements, or similar products within the past 2 weeks
19. Blood donation equal to or above 500 mL within 2 months prior to dosing.
20. Any other finding that, in the judgment of the Investigator, would increase the risk of having an adverse outcome from participating in the study.

Justification to exclude minors: Given that the vast majority of patients with PAH are \>18 years of age and the fact that this is a first in human study, the risks of including children/minors (ie. subjects \< 18 yrs of age) are not justified given the limited potential benefits of including these subjects.

Justification to exclude adults \>60 years old: Subjects \> 60 years of age are more likely to have comorbid medical conditions that could place them at increased risk of participation.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Jason M Elinoff, M.D. — National Heart, Lung, and Blood Institute (NHLBI)
• Study coordinator: Sandra Cooper Bennett, R.N.

Conditions Pulmonary Arterial Hypertension PAH; human monoclonal antibody