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Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF (HFpEF)

Primary Purpose

Heart Failure With Preserved Ejection Fraction

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
HU6
Placebo
Sponsored by
Rivus Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Preserved Ejection Fraction

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adult male or female, ≥40 years of age.
  2. Competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) and must sign the form prior to the initiation of any study procedures.
  3. Body mass index (BMI) ≥30 kg/m2;
  4. Signs and symptoms of HF in the judgement of the Investigator, and meets the following disease severity criteria:

    a. KCCQ OSS ≤80; b. NYHA Classification Class II-III; c. Baseline peak VO2 ≤18 mL/kg/min for females or ≤20 mL/kg/min for males; d. Respiratory exchange ratio (respiratory quotient) (RER [RQ]) at baseline of >1.0; e. Left ventricular ejection fraction (EF) ≥50%; f. At least 1 of the following objective criteria for HF: i. Documented hospitalization with HF as primary cause within in last year, or if greater than the past year, then with addition of structural heart disease on echocardiography (increased left atrial volume size or left ventricular hypertrophy, with sex-specific cut-points as per Lang, 2015) as follows:

    • Left ventricular hypertrophy (LVH):

      1. Men: Either septal wall thickness (cm) either ≥1.1 or posterior wall thickness ≥1.1;
      2. Women: Either septal wall thickness (cm) either ≥ 1.0 or posterior wall thickness ≥1.0;
    • Left atrial dilation (LAD): AP dimension (cm): ≥4.0 in men; >3.8 in women; ii. Pulmonary capillary wedge pressure (PCWP) at rest >15 mmHg (or left ventricular end-diastolic pressure [LVEDP] ≥18 mmHg) or >25 mmHg (or 2.0 mmHg/L/min) with exercise in the last year; iii. E/e' ratio ≥14 at septal annulus at rest on Doppler and tissue Doppler imaging in the last year; or iv. Currently elevated NT-proBNP defined as >125 pg/mL without atrial fibrillation and >350 pg/mL for subjects with chronic controlled atrial fibrillation.
  5. Participants should maintain their stable level of physical activity throughout the duration of the study and must agree to not enroll in an exercise training program during the study.
  6. Participants should maintain their stable diet and no plan to enter into a weight loss program prior to or during the course of the study.
  7. Euthyroid as assessed by a thyroid profile utilizing thyroid stimulating hormone (TSH) and free thyroxine (T4) testing at screening. Subjects with a stable history of thyroid disease and who have been on stable doses of thyroid medications for a minimum of 4 months can be enrolled.
  8. Ambulatory (not wheelchair- or scooter-dependent) and able to perform upright exercise testing including a 6 MWT.
  9. Stable doses of medications (defined as no new medication or change in existing dose of medication ≥50%) for 30 days prior to screening, with additional specific criteria for the diuretics:

    1. If treated with a loop or thiazide diuretic, must be on stable regimen, which dose permits a flexible diuretic dosing schedule.

Exclusion Criteria:

  1. Life expectancy <1 year due to non-cardiovascular reasons, in the judgement of the Investigator.
  2. History of malignancy within 5 years (except non-high-grade skin cancers, carcinoma-in-situ, or low-grade prostate cancer).
  3. Weight change (gain or loss) of ≥10 pounds either by self-reporting or documented weight loss within the past 90 days.
  4. Bariatric surgery prior to screening or planned bariatric surgery during the course of the study.
  5. Treatment with GLP-1 receptor antagonist begun within 1 year of screening.
  6. Treatment with SGLT2 inhibitors begun within 6 months of screening.
  7. Intolerance to MRI or with conditions contraindicated for MRI procedures including but not limited to:

    1. Having surgical clips/metallic implants/shrapnel/internal electric implants; or
    2. Inability to fit into MRI scanner due to subject habitus or exceeding weight tolerance limit of the scanner (generally, 350 or 400 lbs, dependent on manufacturer); or
    3. Claustrophobia: history of severe claustrophobia that would lead to inability to conduct MRI.
  8. Current acute decompensated HF requiring intravenous (IV) diuretics or recent (<1 month before screening) hospitalization for HF.
  9. Primary cardiomyopathy (e.g., constrictive, restrictive, infiltrative, toxic, hypertrophic [congenital], congenital, or any other primary cardiomyopathy, in the judgement of the Investigator.
  10. Active myocarditis (COVID-induced or otherwise).
  11. Active collagen vascular disease.
  12. Current greater than moderate left- or right sided valve disease, in the opinion of the Investigator.
  13. Planned cardiac surgery or catheter intervention during the time of trial participation.
  14. Prior documented EF <40% within the last 3 years.
  15. Tachycardia (>110 beats/minute) at screening.
  16. Atrial fibrillation or atrial flutter with an uncontrolled heart rate response or with a resting heart rate greater than 110 bpm by ECG at screening. Subjects may rescreen after appropriate adjustment of medication to manage the atrial fibrillation. A maximum of 16 subjects with this condition can be enrolled in this study.
  17. Untreated, life-threatening dysrhythmia.

Sites / Locations

  • National Heart InstituteRecruiting
  • Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical CenterRecruiting
  • New Generation of Medical ResearchRecruiting
  • Broward Research Center
  • Northwestern UniversityRecruiting
  • The University of Chicago Medical CenterRecruiting
  • Johns Hopkins UniversityRecruiting
  • Massachusetts General HospitalRecruiting
  • Mayo ClinicRecruiting
  • Saint Luke's Mid America Heart InstituteRecruiting
  • Weill Cornell MedicineRecruiting
  • Wake ForestRecruiting
  • The Lindner Center for Research and Education at The Christ HospitalRecruiting
  • Medical University of South CarolinaRecruiting
  • University of Texas SouthwesternRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active Treatment: HU6 Planned doses of HU6; N = 31

Placebo Comparator Non-active study drug N = 31

Arm Description

Outcomes

Primary Outcome Measures

Evaluate weight reduction while on HU6 treatment
Assess the rate and amount of body weight loss over the course of HU6 treatment

Secondary Outcome Measures

Full Information

First Posted
March 9, 2022
Last Updated
September 27, 2023
Sponsor
Rivus Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05284617
Brief Title
Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF
Acronym
HFpEF
Official Title
Exploratory Phase 2A, Double-blind, Placebo-Controlled, Dose Escalation Study to Determine the Safety, Tolerability, PD, and PK of HU6 for the Treatment of Subjects With Obese Heart Failure With Preserved Ejection Fraction (HFpEF)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 30, 2022 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
October 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rivus Pharmaceuticals, Inc.

4. Oversight

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

5. Study Description

Brief Summary
This is a Phase 2A, randomized, parallel-group, placebo-controlled, double-blind, within subject dose escalation trial with 3 dose levels of HU6 and placebo. Subjects will be randomized (1:1) either to HU6 or placebo. Two dose levels will be administered in sequential order (150 mg daily followed by 300 mg daily), each for 20 days, to reach the third and highest dose of 450 mg daily if safety and tolerability are demonstrated at the lower 2 preceding doses. Administration of the 450 mg high dose will continue for a total of 94 days, with a safety follow-up visit within ~14 days of the last dose.
Detailed Description
This is a Phase 2A, randomized, parallel-group, placebo-controlled, double-blind, within subject dose escalation trial with 3 dose levels of HU6 and placebo. Subjects will be randomized (1:1) either to HU6 or placebo. Two dose levels will be administered in sequential order (150 mg daily followed by 300 mg daily), each for 20 days, to reach the third and highest dose of 450 mg daily if safety and tolerability are demonstrated at the lower 2 preceding doses. Administration of the 450 mg high dose will continue for a total of 94 days, with a safety follow-up visit within ~14 days of the last dose. Subjects will be screened over a 40-day period to determine their eligibility based on specific history, physical, laboratory, and imaging evaluations as per the Schedule of Assessments. While a single screening clinical site visit is indicated, an additional visit may be necessary to complete the screening procedures due to scheduling issues. A number of these assessments will serve as the baseline prior to drug administration. A central laboratory will be used for all assessments, including MRI, DEXA, clinical blood/plasma measures, transthoracic echocardiography, and CPET.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Preserved Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This is a Phase 2A, randomized, parallel-group, placebo-controlled, double-blind, within subject dose escalation trial with 3 dose levels of HU6 and placebo. Subjects will be randomized (1:1) either to HU6 or placebo.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Treatment: HU6 Planned doses of HU6; N = 31
Arm Type
Experimental
Arm Title
Placebo Comparator Non-active study drug N = 31
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
HU6
Intervention Description
HU6 is being evaluated for its efficacy in improving cardiovascular function in obese subjects with HF with preserved ejection fraction (HFpEF).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Evaluate weight reduction while on HU6 treatment
Description
Assess the rate and amount of body weight loss over the course of HU6 treatment
Time Frame
5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult male or female, ≥40 years of age. Competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) and must sign the form prior to the initiation of any study procedures. Body mass index (BMI) ≥30 kg/m2; Signs and symptoms of HF in the judgement of the Investigator, and meets the following disease severity criteria: a. KCCQ OSS ≤80; b. NYHA Classification Class II-III; c. Baseline peak VO2 ≤18 mL/kg/min for females or ≤20 mL/kg/min for males; d. Respiratory exchange ratio (respiratory quotient) (RER [RQ]) at baseline of >1.0; e. Left ventricular ejection fraction (EF) ≥50%; f. At least 1 of the following objective criteria for HF: i. Documented hospitalization with HF as primary cause within in last year, or if greater than the past year, then with addition of structural heart disease on echocardiography (increased left atrial volume size or left ventricular hypertrophy, with sex-specific cut-points as per Lang, 2015) as follows: Left ventricular hypertrophy (LVH): Men: Either septal wall thickness (cm) either ≥1.1 or posterior wall thickness ≥1.1; Women: Either septal wall thickness (cm) either ≥ 1.0 or posterior wall thickness ≥1.0; Left atrial dilation (LAD): AP dimension (cm): ≥4.0 in men; >3.8 in women; ii. Pulmonary capillary wedge pressure (PCWP) at rest >15 mmHg (or left ventricular end-diastolic pressure [LVEDP] ≥18 mmHg) or >25 mmHg (or 2.0 mmHg/L/min) with exercise in the last year; iii. E/e' ratio ≥14 at septal annulus at rest on Doppler and tissue Doppler imaging in the last year; or iv. Currently elevated NT-proBNP defined as >125 pg/mL without atrial fibrillation and >350 pg/mL for subjects with chronic controlled atrial fibrillation. Participants should maintain their stable level of physical activity throughout the duration of the study and must agree to not enroll in an exercise training program during the study. Participants should maintain their stable diet and no plan to enter into a weight loss program prior to or during the course of the study. Euthyroid as assessed by a thyroid profile utilizing thyroid stimulating hormone (TSH) and free thyroxine (T4) testing at screening. Subjects with a stable history of thyroid disease and who have been on stable doses of thyroid medications for a minimum of 4 months can be enrolled. Ambulatory (not wheelchair- or scooter-dependent) and able to perform upright exercise testing including a 6 MWT. Stable doses of medications (defined as no new medication or change in existing dose of medication ≥50%) for 30 days prior to screening, with additional specific criteria for the diuretics: If treated with a loop or thiazide diuretic, must be on stable regimen, which dose permits a flexible diuretic dosing schedule. Exclusion Criteria: Life expectancy <1 year due to non-cardiovascular reasons, in the judgement of the Investigator. History of malignancy within 5 years (except non-high-grade skin cancers, carcinoma-in-situ, or low-grade prostate cancer). Weight change (gain or loss) of ≥10 pounds either by self-reporting or documented weight loss within the past 90 days. Bariatric surgery prior to screening or planned bariatric surgery during the course of the study. Treatment with GLP-1 receptor antagonist begun within 1 year of screening. Treatment with SGLT2 inhibitors begun within 6 months of screening. Intolerance to MRI or with conditions contraindicated for MRI procedures including but not limited to: Having surgical clips/metallic implants/shrapnel/internal electric implants; or Inability to fit into MRI scanner due to subject habitus or exceeding weight tolerance limit of the scanner (generally, 350 or 400 lbs, dependent on manufacturer); or Claustrophobia: history of severe claustrophobia that would lead to inability to conduct MRI. Current acute decompensated HF requiring intravenous (IV) diuretics or recent (<1 month before screening) hospitalization for HF. Primary cardiomyopathy (e.g., constrictive, restrictive, infiltrative, toxic, hypertrophic [congenital], congenital, or any other primary cardiomyopathy, in the judgement of the Investigator. Active myocarditis (COVID-induced or otherwise). Active collagen vascular disease. Current greater than moderate left- or right sided valve disease, in the opinion of the Investigator. Planned cardiac surgery or catheter intervention during the time of trial participation. Prior documented EF <40% within the last 3 years. Tachycardia (>110 beats/minute) at screening. Atrial fibrillation or atrial flutter with an uncontrolled heart rate response or with a resting heart rate greater than 110 bpm by ECG at screening. Subjects may rescreen after appropriate adjustment of medication to manage the atrial fibrillation. A maximum of 16 subjects with this condition can be enrolled in this study. Untreated, life-threatening dysrhythmia.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Boeke
Phone
3037158332
Email
sboeke@rivuspharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Janice Durden
Phone
8435683621
Email
jdurden@rivuspharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shaharyar Khan, PhD
Organizational Affiliation
Rivus Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
National Heart Institute
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesus Castanon
Email
jcastanon@nationalheartinstitute.org
Facility Name
Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olga Barillas
Email
Olga@lundquist.org
Facility Name
New Generation of Medical Research
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33002
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yadilys Perez
Phone
786-803-8417
Email
yadyp@ngmresearch.com
Facility Name
Broward Research Center
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33029
Country
United States
Individual Site Status
Withdrawn
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucia Davis
Email
'lucia.davis@northwestern.edu
Facility Name
The University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Veronica Herzog
Email
Vervherzog@bsd.uchicago.edu
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MJ Lee
Phone
410-502-7310
Email
mlee299@jhmi.edu
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandra Minasian
Email
Aminasian2@mgh.harvard.edu
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Braun
Email
braun.amanda@mayo.edu
Facility Name
Saint Luke's Mid America Heart Institute
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alyssa Boyce-White
Email
aboyce-white@saint-lukes.org
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10012
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Goldstein
Email
cag4020@med.cornell.edu
Facility Name
Wake Forest
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ben Nelson
Phone
336-716-6789
Email
mbnelson@wakehealth.edu
Facility Name
The Lindner Center for Research and Education at The Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Voorhorst
Email
Anne.Voorhorst@thechristhospital.com
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29403
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Renee Baxley
Email
baxleyr@musc.edu
Facility Name
University of Texas Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ayushi Vashisht,
Phone
214-648-9636
Email
ayushi.vashisht@utsouthwestern.edu

12. IPD Sharing Statement

Learn more about this trial

Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF

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