Pulmonary Arterial Hypertension PAHPhase 1NCT05967299
Study of Intravenous ZMA001 in Healthy Subjects
A Phase 1 study testing ZMA001 (BC-NKA-20008) in people with Pulmonary Arterial Hypertension PAH, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: A number of diseases can cause a type of lung injury called pulmonary arterial hypertension (PAH). Most people who develop PAH do not survive more than a few years. A new study drug (ZMA001) may help. ZMA001 is a monoclonal antibody. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension PAH
- What is being tested?
- ZMA001 (BC-NKA-20008)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Nov 2023to 30 Nov 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male* or female, aged 18 to 60 years, inclusive
- In good general health as evidenced by medical history
- 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.
- 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.
Show all 14Show fewer
- Agreement to adhere to Lifestyle Considerations throughout study duration
- 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
Who cannot join
- An individual who meets any of the following criteria prior to informed consent will be excluded from participation in this study:
- 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.
- A history of human immunodeficiency virus (HIV) infection.
- History of severe drug or excipient allergy or hypersensitivity
- Known allergy to any of the components of the investigational drug or placebo
- Recent infection or febrile illness within the past 14 days
Show all 23Show fewer
- Treatment with another investigational drug within the past 30 days or 5 half-lives, whichever is longer
- Any vaccination within the past 4 weeks or receipt of a live-attenuated vaccine within the past 6 months
- Use of tobacco products within the past 3 months
- Illicit drug use (e.g. cocaine, opioids, methamphetamine, PCP) within the past 6 months or positive urine drug screen at Screening Visit
- Marijuana (cannabis) use within the past 30 days or positive urine drug screen at Screening Visit
- History of alcohol abuse within the past 2 years
- 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
- Body mass index less than 17 or greater than 32 kg/m^2
- Clinically significant abnormal results on clinical blood testing completed at the Screening Visit
- Electrocardiographic evidence of clinically relevant heart disease
- Diabetes mellitus requiring medical treatment
- Received another monoclonal antibody in the past 30 days
- Use of herbal supplements, or similar products within the past 2 weeks
- Blood donation equal to or above 500 mL within 2 months prior to dosing.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: A Phase 1 Single-Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Intravenous ZMA001 in Healthy Subjects
Background:
A number of diseases can cause a type of lung injury called pulmonary arterial hypertension (PAH). Most people who develop PAH do not survive more than a few years. A new study drug (ZMA001) may help. ZMA001 is a monoclonal antibody. This type of drug consists of proteins, made in a facility, that are very similar to proteins in a human body. But before giving ZMA001 to people sick with PAH, researchers want to find out how the drug affects healthy people.
Read more
Objective:
To test a drug (ZMA001) in healthy volunteers.
Eligibility:
Healthy adults aged 18 to 60 years.
Design:
Participants will be screened. They will have a physical exam with blood tests. They will have a urine test for drug use. They will have a test of their heart function.
Participants will come to the clinic for 1 inpatient visit of up to 48 hours.
ZMA001 is a liquid administered through a tube attached to a needle inserted into a vein in the arm. Participants will receive this drug only once, during their inpatient stay. Some participants will receive the drug; others will receive a placebo in Cohort 1 only. A placebo is a treatment that looks just like the real drug but contains no medicine. Participants will not know which treatment they are getting in Cohort 1. Cohorts 2-4 will receive a single dose of the study drug, administered through a tube attached to a needle inserted into a vein in the arm.
After a screening visit, participants will have 1 inpatient visit and up to 8 outpatient visits over 16 weeks after receiving the treatment. Blood draws and other tests will be repeated. Each outpatient visit is approximately 2 hours long.
This study is the first time ZMA001 will be administered to people.
Read the detailed description
Study Description:
ZMA001 is a fully human, monoclonal antibody (IgG1) that inhibits migration of activated monocytes and macrophages and reduces pulmonary vascular remodeling and pulmonary artery pressure in pre-clinical rodent models of pulmonary arterial hypertension (PAH). The current first-in-human, single ascending-dose study will determine the safety, tolerability, and pharmacokinetics of intravenous ZMA001 in healthy subjects.
Objectives:
Primary Objective: Safety and tolerability of ZMA001 in healthy subjects
Secondary Objectives: Determine the pharmacokinetics of ZMA001 in healthy subjects following a single, intravenous dose
Endpoints:
Primary Endpoint: The number of all-cause, treatment-emergent adverse events, grade 1 and above (following CTCAE v5.0 criteria) through day 113
Secondary Endpoints: For each ZMA001 dose level (1.5, 0.25, 0.50, and 1.0 mg/kg), the following will be determined [Timeframe: Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8, 15, 22, 29, 57, 85 and 113]:
- Time to peak drug concentration (Tmax)
- Peak drug concentration (Cmax)
- Area under the drug concentration-time curve (AUC)
- Elimination half-life
- Conditions
- Pulmonary Arterial Hypertension PAH
- Being tested
- Placebo Cohort 1 (1.5 mg/kg/dose) only, ZMA001 (BC-NKA-20008)
- Keywords
- human monoclonal antibody (IgG1)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo Cohort 1 (1.5 mg/kg/dose) onlyOther
30mg/ml Sucrose
ZMA001 (BC-NKA-20008)Drug
ZMA001 is a fully human, monoclonal antibody (IgG1) that inhibits migration of activated monocytes and macrophages and reduces pulmonary vascular remodeling and pulmonary artery pressure in pre-clinical rodent models of pulmonary arterial hypertension (PAH).
| Study group | Role | What they receive |
|---|---|---|
| Placebo Cohort 1 (1.5 mg/kg/dose) only | Placebo comparator | Placebo for ZMA001 is supplied in a single-use 10 mL glass vial. Each vial contains 30 mg/mL of sucrose.Placebo drug is manufactured using the same ingredients as active drug (20 mM histidine-HCl buffer [pH 5.6], 30 mg/mL sucrose, 0.070 w/v% polysorbate 80) excluding ZMA001 antibody and is packed in the same vial. Receives: Other: Placebo Cohort 1 (1.5 mg/kg/dose) only |
| ZMA001 (BC-NKA-20008) | Experimental | ZMA001 is a fully human, monoclonal antibody (IgG1) that inhibits migration of activated monocytes and macrophages and reduces pulmonary vascular remodeling and pulmonary artery pressure in pre-clinical rodent models of pulmonary arterial hypertension (PAH). Receives: Drug: ZMA001 (BC-NKA-20008) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of ZMA001 in healthy subjects
The number of all-cause, treatment-emergent adverse events, grade 1 and above (following CTCAE v5.0 criteria) through day 113
Measured: day 113
Secondary outcomes (3)
Determine the pharmacokinetics of ZMA001 in healthy subjects following a single, intravenous dose.
For each ZMA001 dose level (1.5, 0.25, 0.50, and 1.0 mg/kg), the following will be determined.3. Area under the drug concentration-time curve(AUC)
Measured: Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8, 15, 22, 29, 57, 85 and 113
Determine the pharmacokinetics of ZMA001 in healthy subjects following a single, intravenous dose.
For each ZMA001 dose level (1.5, 0.25, 0.50, and 1.0 mg/kg), the following will be determined.2. Peak drug concentration (Cmax)
Measured: Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8, 15, 22, 29, 57, 85 and 113
Determine the pharmacokinetics of ZMA001 in healthy subjects following a single, intravenous dose.
For each ZMA001 dose level (1.5, 0.25, 0.50, and 1.0 mg/kg), the following will be determined.1. Time to peak drug concentration (Tmax)
Measured: Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8, 15, 22, 29, 57, 85 and 113
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2023
- Study start27 Nov 2023
- Primary completion1 Sep 2027 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial Hypertension PAHStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Zymedi, Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Jason M Elinoff, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05967299
- Sponsor's protocol ID
- 10001522
- Other IDs
- 001522-H
- Status last verified
- 1 Oct 2026
- First submitted
- 27 Jul 2023
- Last updated
- 5 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication.