A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 in Healthy Adult Volunteers and Mildly Hypertensive Participants

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Two-Part, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 (an Anti-REGN5381 Antibody and Reversal Agent) and REGN5381 (an NPR1 Agonist Antibody) When Administered Alone or in Sequence to Healthy Volunteers and Mildly Hypertensive Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05291546
• Other study ID #: R9035-HV-2125
• Secondary ID: 2021-005174-26
• Status: Completed
• Phase: Phase 1
• Start date: April 13, 2022
• Est. completion date: April 2, 2024

Study information

• Verified date: April 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to:

• Evaluate the safety and tolerability of REGN5381 and REGN9035 administered alone or sequentially.

The secondary objectives of the study are to:

• Evaluate the ability of single intravenous (IV) doses of REGN9035 (compared to placebo) to reverse the acute hemodynamic effects of REGN5381

• Evaluate the hemodynamic effects of single IV doses of REGN5381

• Evaluate the persistence of the hemodynamic effects of single IV doses of REGN5381 and the reversal of REGN5381 effects by REGN9035 (compared to placebo)

• Evaluate the pharmacokinetics of single IV doses of REGN5381 and REGN9035 administered alone or sequentially

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: April 2, 2024
• Est. primary completion date: April 2, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Key Inclusion Criteria:

1. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the screening visit.

2. Normal or mildly elevated blood pressure as defined in the protocol.

Key Exclusion Criteria:

1. History of unexplained syncope or autonomic dysfunction.

2. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease.

3. Protocol-defined risk factors for cardiovascular disease.

Note: Other protocol defined inclusion / exclusion criteria apply

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• REGN9035
Part A: Single dose administered by IV infusion on day 1. Part B: Selected doses administered by IV infusion on day 2 or 22.
• REGN5381
Part B: Selected doses administered by IV infusion on day 1.

Other:
• Placebo
Part A: Single dose administered by IV infusion on day1. Part B: Single dose administered by IV infusion on day 1, day 2 and/or day 22.

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Leuven Gasthuisberg Campus	Leuven
Germany	Charite Research Organisation GmbH	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)		Up to Day 162
Secondary	Mean systolic blood pressure (SBP) obtained after study drug administration	Up to 24 hours after study drug administration.	Up to Day 3
Secondary	Mean diastolic blood pressure (DBP) obtained after study drug administration		Up to Day 3
Secondary	Mean arterial pressure (MAP) obtained after study drug administration		Up to Day 3
Secondary	Mean pulse pressure (PP) obtained after study drug administration		Up to Day 3
Secondary	Mean pulse rate (PR) obtained after study drug administration		Up to Day 3
Secondary	Mean stroke volume (SV) obtained after study drug administration		Up to Day 3
Secondary	Absolute change in the mean SBP obtained after study drug administration		Up to Day 3
Secondary	Absolute change in the mean DBP obtained after study drug administration		Up to Day 3
Secondary	Absolute change in the mean MAP obtained after study drug administration		Up to Day 3
Secondary	Absolute change in the mean PP obtained after study drug administration		Up to Day 3
Secondary	Absolute change in the mean PR obtained after study drug administration		Up to Day 3
Secondary	Absolute change in the mean SV obtained after study drug administration		Up to Day 3
Secondary	Maximum change in the mean SBP obtained after study drug administration		Up to Day 3
Secondary	Maximum change in the mean DBP obtained after study drug administration		Up to Day 3
Secondary	Maximum change in the mean MAP obtained after study drug administration		Up to Day 3
Secondary	Maximum change in the mean PP obtained after study drug administration		Up to Day 3
Secondary	Maximum change in the mean PR obtained after study drug administration		Up to Day 3
Secondary	Maximum change in the mean SV obtained after study drug administration		Up to Day 3
Secondary	Percent change in the mean SBP obtained after study drug administration		Up to Day 3
Secondary	Percent change in the mean DBP obtained after study drug administration		Up to Day 3
Secondary	Percent change in the mean MAP obtained after study drug administration		Up to Day 3
Secondary	Percent change in the mean PP obtained after study drug administration		Up to Day 3
Secondary	Percent change in the mean PR obtained after study drug administration		Up to Day 3
Secondary	Percent change in the mean SV obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (post-REGN5381 administration) in the mean SBP obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (post-REGN5381 administration) in the mean DBP obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (post-REGN5381 administration) in the mean MAP obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (post-REGN5381 administration) in the mean PP obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (post-REGN5381 administration) in the mean PR obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (post-REGN administration) in the mean SBP obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (post-REGN administration) in the mean DBP obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (post-REGN administration) in the mean MAP obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (post-REGN administration) in the mean PP obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (post-REN5381 administration) in the mean SBP obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (post-REN5381 administration) in the mean DBP obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (post-REN5381 administration) in the mean MAP obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (post-REN5381 administration) in the mean PP obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (post-REN5381 administration) in the mean SV obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (pre-REGN5381 administration) in the mean SBP obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (pre-REGN5381 administration) in the mean DBP obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (pre-REGN5381 administration) in the mean MAP obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (pre-REGN5381 administration) in the mean PP obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (pre-REGN5381 administration) in the mean PR obtained after study drug administration		Up to Day 3
Secondary	Absolute change from baseline (pre-REGN5381 administration) in the mean SV obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (pre-REGN administration) in the mean SBP obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (pre-REGN administration) in the mean DBP obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (pre-REGN administration) in the mean MAP obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (pre-REGN administration) in the mean PP obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (pre-REGN administration) in the mean PR obtained after study drug administration		Up to Day 3
Secondary	Maximum change from baseline (pre-REGN administration) in the mean SV obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (pre-REN5381 administration) in the mean SBP obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (pre-REN5381 administration) in the mean DBP obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (pre-REN5381 administration) in the mean MAP obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (pre-REN5381 administration) in the mean PP obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (pre-REN5381 administration) in the mean PR obtained after study drug administration		Up to Day 3
Secondary	Percent change from baseline (pre-REN5381 administration) in the mean SV obtained after study drug administration		Up to Day 3
Secondary	Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SBP obtained after study drug administration.		Baseline to Day 3
Secondary	Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) DBP obtained after study drug administration.		Baseline to Day 3
Secondary	Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) MAP obtained after study drug administration.		Baseline to Day 3
Secondary	Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PP obtained after study drug administration.		Baseline to Day 3
Secondary	Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PR obtained after study drug administration.		Baseline to Day 3
Secondary	Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SV obtained after study drug administration.		Baseline to Day 3
Secondary	Time to return to within 10% of baseline (pre-REGN5381) SBP		Up to approximately Day 162
Secondary	Time to return to within 10% of baseline (pre-REGN5381) DBP		Up to approximately Day 162
Secondary	Time to return to within 10% of baseline (pre-REGN5381) MAP		Up to approximately Day 162
Secondary	Time to return to within 10% of baseline (pre-REGN5381) PP		Up to approximately Day 162
Secondary	Time to return to within 10% of baseline (pre-REGN5381) PR		Up to approximately Day 162
Secondary	Time to return to within 10% of baseline (pre-REGN5381) SV		Up to approximately Day 162
Secondary	SBP		Through Day 36
Secondary	DBP		Through Day 36
Secondary	MAP		Through Day 36
Secondary	PP		Through Day 36
Secondary	PR		Through Day 36
Secondary	Absolute change from baseline in SBP		Through Day 36
Secondary	Absolute change from baseline in DBP		Through Day 36
Secondary	Absolute change from baseline in MAP		Through Day 36
Secondary	Absolute change from baseline in PP		Through Day 36
Secondary	Absolute change from baseline in PR		Through Day 36
Secondary	Percent change from baseline in SBP		Through Day 36
Secondary	Percent change from baseline in DBP		Through Day 36
Secondary	Percent change from baseline in MAP		Through Day 36
Secondary	Percent change from baseline in PP		Through Day 36
Secondary	Percent change from baseline in PR		Through Day 36
Secondary	Concentrations of total REGN9035		Up to Day 162
Secondary	Concentrations of total REGN5381 over time		Up to Day 162
Secondary	Concentrations of total REGN9035 and/or total REGN5381		Up to Day 162