Clinical trial NCT05291546: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 in Healthy Adult Volunteers and Mildly Hypertensive Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Healthy Volunteers
Mild Hypertension
High Blood Pressure
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-03-22
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 162
Secondary outcomes:
measure: Mean systolic blood pressure (SBP) obtained after study drug administration
timeFrame: Up to Day 3
measure: Mean diastolic blood pressure (DBP) obtained after study drug administration
timeFrame: Up to Day 3
measure: Mean arterial pressure (MAP) obtained after study drug administration
timeFrame: Up to Day 3
measure: Mean pulse pressure (PP) obtained after study drug administration
timeFrame: Up to Day 3
measure: Mean pulse rate (PR) obtained after study drug administration
timeFrame: Up to Day 3
measure: Mean stroke volume (SV) obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change in the mean SBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change in the mean DBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change in the mean MAP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change in the mean PP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change in the mean PR obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change in the mean SV obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change in the mean SBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change in the mean DBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change in the mean MAP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change in the mean PP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change in the mean PR obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change in the mean SV obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change in the mean SBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change in the mean DBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change in the mean MAP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change in the mean PP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change in the mean PR obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change in the mean SV obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (post-REGN5381 administration) in the mean SBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (post-REGN5381 administration) in the mean DBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (post-REGN5381 administration) in the mean MAP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (post-REGN5381 administration) in the mean PP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (post-REGN5381 administration) in the mean PR obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (post-REGN administration) in the mean SBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (post-REGN administration) in the mean DBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (post-REGN administration) in the mean MAP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (post-REGN administration) in the mean PP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (post-REN5381 administration) in the mean SBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (post-REN5381 administration) in the mean DBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (post-REN5381 administration) in the mean MAP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (post-REN5381 administration) in the mean PP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (post-REN5381 administration) in the mean SV obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (pre-REGN5381 administration) in the mean SBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (pre-REGN5381 administration) in the mean DBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (pre-REGN5381 administration) in the mean MAP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (pre-REGN5381 administration) in the mean PP obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (pre-REGN5381 administration) in the mean PR obtained after study drug administration
timeFrame: Up to Day 3
measure: Absolute change from baseline (pre-REGN5381 administration) in the mean SV obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (pre-REGN administration) in the mean SBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (pre-REGN administration) in the mean DBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (pre-REGN administration) in the mean MAP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (pre-REGN administration) in the mean PP obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (pre-REGN administration) in the mean PR obtained after study drug administration
timeFrame: Up to Day 3
measure: Maximum change from baseline (pre-REGN administration) in the mean SV obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (pre-REN5381 administration) in the mean SBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (pre-REN5381 administration) in the mean DBP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (pre-REN5381 administration) in the mean MAP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (pre-REN5381 administration) in the mean PP obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (pre-REN5381 administration) in the mean PR obtained after study drug administration
timeFrame: Up to Day 3
measure: Percent change from baseline (pre-REN5381 administration) in the mean SV obtained after study drug administration
timeFrame: Up to Day 3
measure: Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SBP obtained after study drug administration.
timeFrame: Baseline to Day 3
measure: Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) DBP obtained after study drug administration.
timeFrame: Baseline to Day 3
measure: Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) MAP obtained after study drug administration.
timeFrame: Baseline to Day 3
measure: Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PP obtained after study drug administration.
timeFrame: Baseline to Day 3
measure: Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PR obtained after study drug administration.
timeFrame: Baseline to Day 3
measure: Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SV obtained after study drug administration.
timeFrame: Baseline to Day 3
measure: Time to return to within 10% of baseline (pre-REGN5381) SBP
timeFrame: Up to approximately Day 162
measure: Time to return to within 10% of baseline (pre-REGN5381) DBP
timeFrame: Up to approximately Day 162
measure: Time to return to within 10% of baseline (pre-REGN5381) MAP
timeFrame: Up to approximately Day 162
measure: Time to return to within 10% of baseline (pre-REGN5381) PP
timeFrame: Up to approximately Day 162
measure: Time to return to within 10% of baseline (pre-REGN5381) PR
timeFrame: Up to approximately Day 162
measure: Time to return to within 10% of baseline (pre-REGN5381) SV
timeFrame: Up to approximately Day 162
measure: SBP
timeFrame: Through Day 36
measure: DBP
timeFrame: Through Day 36
measure: MAP
timeFrame: Through Day 36
measure: PP
timeFrame: Through Day 36
measure: PR
timeFrame: Through Day 36
measure: Absolute change from baseline in SBP
timeFrame: Through Day 36
measure: Absolute change from baseline in DBP
timeFrame: Through Day 36
measure: Absolute change from baseline in MAP
timeFrame: Through Day 36
measure: Absolute change from baseline in PP
timeFrame: Through Day 36
measure: Absolute change from baseline in PR
timeFrame: Through Day 36
measure: Percent change from baseline in SBP
timeFrame: Through Day 36
measure: Percent change from baseline in DBP
timeFrame: Through Day 36
measure: Percent change from baseline in MAP
timeFrame: Through Day 36
measure: Percent change from baseline in PP
timeFrame: Through Day 36
measure: Percent change from baseline in PR
timeFrame: Through Day 36
measure: Concentrations of total REGN9035
timeFrame: Up to Day 162
measure: Concentrations of total REGN5381 over time
timeFrame: Up to Day 162
measure: Concentrations of total REGN9035 and/or total REGN5381
timeFrame: Up to Day 162
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven Gasthuisberg Campus
city: Berlin
country: Germany
facility: Charite Research Organisation GmbH
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: