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Safety and Tolerability of Single Ascending Intravenous (IV) Doses of REGN5381 in Adult Heart Failure Patients With Elevated Pulmonary Capillary Wedge Pressure

Primary Purpose

Heart Failure

Status
Suspended
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
REGN5381
Placebo
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring New York Heart Association (NYHA) class II/III, Elevated Pulmonary Capillary Wedge Pressure, Reduced Left Ventricular Ejection Fraction

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  1. Body mass index (BMI) between 18 and 35 kg/m2, inclusive, rounded to the nearest whole number
  2. Ambulatory patients with New York Heart Association (NYHA) class II/III heart failure and at least 1 sign and/or symptom of congestion (eg, dyspnea on exertion, worsening edema, orthopnea, etc.)
  3. Left ventricular ejection fraction (LVEF) <50% on echocardiogram (ie, HFrEF patients) within 6 months prior to randomization (only for Group A and Group B)
  4. Left ventricular ejection fraction (LVEF) ≥50% on echocardiogram (ie, HFpEF patients) within 6 months prior to randomization (only for Group C)
  5. NT-proBNP >1000 pg/mL or Brain Natriuretic Peptide (active form) (BNP) >300 pg/mL as described in the protocol within 30 days prior to randomization measured by the local laboratory
  6. Pulmonary capillary wedge pressure (PCWP) ≥15 mmHg ans Right artrail pressure (RAP >5 on right heart catheterization (RHC) the morning of anticipated study drug dose administration
  7. Systolic blood pressure (SBP) ≥100 mmHg at the screening visit and on day -1
  8. Hematocrit >30% at the screening visit and day -1

Key Exclusion Criteria:

  1. Currently taking IV vasodilators and/or inotropes
  2. Taking sacubitril/valsartan (only for Group A and Group C)
  3. Taking a phosphodiesterase (PDE) inhibitor (eg, sildenafil), or a soluble guanylate cyclase stimulator (SGCS; ie, vericiguat) within 2 weeks of the screening visit or planning on taking valsartan/sacubitril, a PDE inhibitor, or a SGCS at any point during the study
  4. More than moderate valvular regurgitation/stenosis on echocardiogram within 6 months prior to randomization
  5. Known infiltrative or hypertrophic cardiomyopathy
  6. Acute coronary syndrome within prior 6 months of randomization
  7. History of cardiac arrest
  8. Cardiac surgery within 3 months of randomization
  9. Pacemaker or defibrillator placement within prior 30 days of randomization
  10. Severe chronic obstructive pulmonary disease (COPD) (defined as Forced Expiratory Volume in 1st second [FEV1] <50% of predicted or Global Initiative for Chronic Obstructive Lung Disease [GOLD] 3 or 4)
  11. Pulmonary arterial hypertension (World Health Organization [WHO] Group 1)
  12. Congenital heart disease (repaired or unrepaired)
  13. Inability to lie flat for cardiac catheterization

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Sites / Locations

  • Universitaire Ziekenhuizen (UZ) Leuven - Campus Gasthuisberg
  • ZOL Genk
  • Gottsegen National Cardiovascular Center
  • Magyar Honvedseg Egeszsegugyi Kozpont
  • ARENSIA Exploratory Medicine at the Republican Clinical Hospital
  • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
  • Bieganski Hospital
  • Klinika Kardiologii
  • Gornoslaskie Centrum Medyczne Szpital W Ochojcu
  • Central Clinical Hospital
  • Arensia Monza Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group A

Group B

Group C

Arm Description

Randomized 3:1; limited to patients with heart failure with reduced ejection fraction (HFrEF) not taking sacubitril/valsartan

Randomized 3:1; limited to patients with HFrEF taking sacubitril/valsartan

Randomized 3:1; limited to patients with HFpEF (not taking sacubitril/valsartan)

Outcomes

Primary Outcome Measures

Incidence and severity of treatment-emergent adverse events (TEAEs)

Secondary Outcome Measures

Change from baseline in pulmonary capillary wedge pressure (PCWP)
Change from baseline right atrial pressure (RAP)
Change from baseline cardiac output (CO)
Change from baseline systemic vascular resistance (SVR)
Change from baseline mean pulmonary artery pressure (mPAP)
Change from baseline pulmonary vascular resistance (PVR)
Change from baseline in systolic blood pressure (SBP)
Change from baseline in diastolic blood pressure (DBP)
Change from baseline in mean arterial pressure (MAP)
Change from baseline in pulse rate (PR)
Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)
Concentrations of REGN5381 in serum
Immunogenicity, as measured by anti-drug antibodies (ADA) to REGN5381

Full Information

First Posted
April 25, 2022
Last Updated
June 1, 2023
Sponsor
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05353166
Brief Title
Safety and Tolerability of Single Ascending Intravenous (IV) Doses of REGN5381 in Adult Heart Failure Patients With Elevated Pulmonary Capillary Wedge Pressure
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of REGN5381, an NPR1 Agonist, in Heart Failure Patients With Elevated Pulmonary Capillary Wedge Pressure
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Suspended
Why Stopped
Study pausing criteria were met
Study Start Date
June 30, 2022 (Actual)
Primary Completion Date
December 28, 2023 (Anticipated)
Study Completion Date
December 28, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of the study is to evaluate the safety and tolerability of single doses of REGN5381 in patients with heart failure with evidence of congestion The secondary objectives of the study are to: Evaluate the effects of single doses of REGN5381 on hemodynamic parameters Evaluate the effects of REGN5381 on a clinical biomarker of heart failure severity Characterize the pharmacokinetics (PK) of single doses of REGN5381 Assess the immunogenicity of REGN5381

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
New York Heart Association (NYHA) class II/III, Elevated Pulmonary Capillary Wedge Pressure, Reduced Left Ventricular Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
149 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Description
Randomized 3:1; limited to patients with heart failure with reduced ejection fraction (HFrEF) not taking sacubitril/valsartan
Arm Title
Group B
Arm Type
Experimental
Arm Description
Randomized 3:1; limited to patients with HFrEF taking sacubitril/valsartan
Arm Title
Group C
Arm Type
Experimental
Arm Description
Randomized 3:1; limited to patients with HFpEF (not taking sacubitril/valsartan)
Intervention Type
Drug
Intervention Name(s)
REGN5381
Intervention Description
Single dose administered via IV infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Single dose administered via IV infusion
Primary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame
Through the end-of-study (EOS) visit up to 78 days post-dose
Secondary Outcome Measure Information:
Title
Change from baseline in pulmonary capillary wedge pressure (PCWP)
Time Frame
Over 6 hours post-dose administration
Title
Change from baseline right atrial pressure (RAP)
Time Frame
Over 6 hours post-dose administration
Title
Change from baseline cardiac output (CO)
Time Frame
Over 6 hours post-dose administration
Title
Change from baseline systemic vascular resistance (SVR)
Time Frame
Over 6 hours post-dose administration
Title
Change from baseline mean pulmonary artery pressure (mPAP)
Time Frame
Over 6 hours post-dose administration
Title
Change from baseline pulmonary vascular resistance (PVR)
Time Frame
Over 6 hours post-dose administration
Title
Change from baseline in systolic blood pressure (SBP)
Time Frame
Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 78 days post-dose
Title
Change from baseline in diastolic blood pressure (DBP)
Time Frame
Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 78 days post-dose
Title
Change from baseline in mean arterial pressure (MAP)
Time Frame
Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 78 days post-dose
Title
Change from baseline in pulse rate (PR)
Time Frame
Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 78 days post-dose
Title
Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)
Time Frame
To 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 78 days post-dose
Title
Concentrations of REGN5381 in serum
Time Frame
Through the EOS visit, up to 78 days post-dose
Title
Immunogenicity, as measured by anti-drug antibodies (ADA) to REGN5381
Time Frame
Through the EOS visit, up to 78 days post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Body mass index (BMI) between 18 and 35 kg/m2, inclusive, rounded to the nearest whole number Ambulatory patients with New York Heart Association (NYHA) class II/III heart failure and at least 1 sign and/or symptom of congestion (eg, dyspnea on exertion, worsening edema, orthopnea, etc.) Left ventricular ejection fraction (LVEF) <50% on echocardiogram (ie, HFrEF patients) within 6 months prior to randomization (only for Group A and Group B) Left ventricular ejection fraction (LVEF) ≥50% on echocardiogram (ie, HFpEF patients) within 6 months prior to randomization (only for Group C) NT-proBNP >1000 pg/mL or Brain Natriuretic Peptide (active form) (BNP) >300 pg/mL as described in the protocol within 30 days prior to randomization measured by the local laboratory Pulmonary capillary wedge pressure (PCWP) ≥15 mmHg ans Right artrail pressure (RAP >5 on right heart catheterization (RHC) the morning of anticipated study drug dose administration Systolic blood pressure (SBP) ≥100 mmHg at the screening visit and on day -1 Hematocrit >30% at the screening visit and day -1 Key Exclusion Criteria: Currently taking IV vasodilators and/or inotropes Taking sacubitril/valsartan (only for Group A and Group C) Taking a phosphodiesterase (PDE) inhibitor (eg, sildenafil), or a soluble guanylate cyclase stimulator (SGCS; ie, vericiguat) within 2 weeks of the screening visit or planning on taking valsartan/sacubitril, a PDE inhibitor, or a SGCS at any point during the study More than moderate valvular regurgitation/stenosis on echocardiogram within 6 months prior to randomization Known infiltrative or hypertrophic cardiomyopathy Acute coronary syndrome within prior 6 months of randomization History of cardiac arrest Cardiac surgery within 3 months of randomization Pacemaker or defibrillator placement within prior 30 days of randomization Severe chronic obstructive pulmonary disease (COPD) (defined as Forced Expiratory Volume in 1st second [FEV1] <50% of predicted or Global Initiative for Chronic Obstructive Lung Disease [GOLD] 3 or 4) Pulmonary arterial hypertension (World Health Organization [WHO] Group 1) Congenital heart disease (repaired or unrepaired) Inability to lie flat for cardiac catheterization Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Universitaire Ziekenhuizen (UZ) Leuven - Campus Gasthuisberg
City
Leuven
State/Province
Flemish Brabant
ZIP/Postal Code
3000
Country
Belgium
Facility Name
ZOL Genk
City
Genk
State/Province
Limburg
ZIP/Postal Code
3600
Country
Belgium
Facility Name
Gottsegen National Cardiovascular Center
City
Budapest
State/Province
Pest
ZIP/Postal Code
1096
Country
Hungary
Facility Name
Magyar Honvedseg Egeszsegugyi Kozpont
City
Budapest
State/Province
Pest
ZIP/Postal Code
1134
Country
Hungary
Facility Name
ARENSIA Exploratory Medicine at the Republican Clinical Hospital
City
Chișinău
ZIP/Postal Code
2025
Country
Moldova, Republic of
Facility Name
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
City
Wrocław
State/Province
Dolny Śląsk
ZIP/Postal Code
50-556
Country
Poland
Facility Name
Bieganski Hospital
City
Lodz
State/Province
Lodz Voivodeship
ZIP/Postal Code
91-347
Country
Poland
Facility Name
Klinika Kardiologii
City
Białystok
State/Province
Podlasie
ZIP/Postal Code
15-276
Country
Poland
Facility Name
Gornoslaskie Centrum Medyczne Szpital W Ochojcu
City
Katowice
ZIP/Postal Code
40-635
Country
Poland
Facility Name
Central Clinical Hospital
City
Lodz
ZIP/Postal Code
92-213
Country
Poland
Facility Name
Arensia Monza Medical Center
City
Bucharest
ZIP/Postal Code
011658
Country
Romania

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
IPD Sharing Time Frame
When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
IPD Sharing Access Criteria
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
IPD Sharing URL
https://vivli.org/

Learn more about this trial

Safety and Tolerability of Single Ascending Intravenous (IV) Doses of REGN5381 in Adult Heart Failure Patients With Elevated Pulmonary Capillary Wedge Pressure

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