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Study of Intravenous ZMA001 in Healthy Subjects

Phase 1
Suspended
Conditions
Pulmonary Arterial Hypertension PAH
Interventions
Other: Placebo
Drug: ZMA001 (BC-NKA-20008)
Registration Number
NCT05967299
Lead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Brief 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. 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.

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. 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.

After a screening visit, participants will have 1 inpatient visit and up to 6 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.

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, randomized, double-blind, placebo-controlled, 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, 5, 12 and 20 mg/kg), the following will be determined \[Timeframe: Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8, 29, 57, 85 and 113\]:

1. Time to peak drug concentration (Tmax)

2. Peak drug concentration (Cmax)

3. Area under the drug concentration-time curve (AUC)

4. Elimination half-life

Recruitment & Eligibility

Status
SUSPENDED
Sex
All
Target Recruitment
20
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo 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.
ZMA001 (BC-NKA-20008)ZMA001 (BC-NKA-20008)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).
Primary Outcome Measures
NameTimeMethod
Safety and tolerability of ZMA001 in healthy subjectsday 113

The number of all-cause, treatment-emergent adverse events, grade 1 and above (following CTCAE v5.0 criteria) through day 113

Secondary Outcome Measures
NameTimeMethod
Determine the pharmacokinetics of ZMA001 in healthy subjects following a single, intravenous dose.Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8, 29, 57, 85 and 113

For each ZMA001 dose level (1.5, 5, 12, and 20mg/kg), the following will be determined1. Time to peak drug concentration (Tmax)2. Peak drug concentration (Cmax)3. Area under the drug concentration-time curve(AUC)

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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