Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF
- Conditions
- Heart Failure With Preserved Ejection Fraction
- Registration Number
- NCT05284617
- Lead Sponsor
- Rivus Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 67
Inclusion Criteria:<br><br> 1. Adult male or female, =40 years of age.<br><br> 2. Competent to understand the information given in the Institutional Review Board<br> (IRB) or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) and<br> must sign the form prior to the initiation of any study procedures.<br><br> 3. Body mass index (BMI) =30 kg/m2;<br><br> 4. Signs and symptoms of HF in the judgement of the Investigator, and meets the<br> following disease severity criteria:<br><br> a. KCCQ OSS =80; b. NYHA Classification Class II-III; c. Baseline peak VO2 =18<br> mL/kg/min for females or =20 mL/kg/min for males; d. Respiratory exchange ratio<br> (respiratory quotient) (RER [RQ]) at baseline of >1.0; e. Left ventricular ejection<br> fraction (EF) =50%; f. At least 1 of the following objective criteria for HF: i.<br> Documented hospitalization with HF as primary cause within in last year, or if<br> greater than the past year, then with addition of structural heart disease on<br> echocardiography (increased left atrial volume size or left ventricular hypertrophy,<br> with sex-specific cut-points as per Lang, 2015) as follows:<br><br> - Left ventricular hypertrophy (LVH):<br><br> 1. Men: Either septal wall thickness (cm) either =1.1 or posterior wall<br> thickness =1.1;<br><br> 2. Women: Either septal wall thickness (cm) either = 1.0 or posterior wall<br> thickness =1.0;<br><br> - Left atrial dilation (LAD): AP dimension (cm): =4.0 in men; >3.8 in women; ii.<br> Pulmonary capillary wedge pressure (PCWP) at rest >15 mmHg (or left ventricular<br> end-diastolic pressure [LVEDP] =18 mmHg) or >25 mmHg (or 2.0 mmHg/L/min) with<br> exercise in the last year; iii. E/e' ratio =14 at septal annulus at rest on<br> Doppler and tissue Doppler imaging in the last year; or iv. Currently elevated<br> NT-proBNP defined as >125 pg/mL without atrial fibrillation and >350 pg/mL for<br> subjects with chronic controlled atrial fibrillation.<br><br> 5. Participants should maintain their stable level of physical activity throughout the<br> duration of the study and must agree to not enroll in an exercise training program<br> during the study.<br><br> 6. Participants should maintain their stable diet and no plan to enter into a weight<br> loss program prior to or during the course of the study.<br><br> 7. Euthyroid as assessed by a thyroid profile utilizing thyroid stimulating hormone<br> (TSH) and free thyroxine (T4) testing at screening. Subjects with a stable history<br> of thyroid disease and who have been on stable doses of thyroid medications for a<br> minimum of 4 months can be enrolled.<br><br> 8. Ambulatory (not wheelchair- or scooter-dependent) and able to perform upright<br> exercise testing including a 6 MWT.<br><br> 9. Stable doses of medications (defined as no new medication or change in existing dose<br> of medication =50%) for 30 days prior to screening, with additional specific<br> criteria for the diuretics:<br><br> 1. If treated with a loop or thiazide diuretic, must be on stable regimen, which<br> dose permits a flexible diuretic dosing schedule.<br><br>Exclusion Criteria:<br><br> 1. Life expectancy <1 year due to non-cardiovascular reasons, in the judgement of the<br> Investigator.<br><br> 2. History of malignancy within 5 years (except non-high-grade skin cancers,<br> carcinoma-in-situ, or low-grade prostate cancer).<br><br> 3. Weight change (gain or loss) of =10 pounds either by self-reporting or documented<br> weight loss within the past 90 days.<br><br> 4. Bariatric surgery prior to screening or planned bariatric surgery during the course<br> of the study.<br><br> 5. Treatment with GLP-1 receptor antagonist begun within 1 year of screening.<br><br> 6. Treatment with SGLT2 inhibitors begun within 6 months of screening.<br><br> 7. Intolerance to MRI or with conditions contraindicated for MRI procedures including<br> but not limited to:<br><br> 1. Having surgical clips/metallic implants/shrapnel/internal electric implants; or<br><br> 2. Inability to fit into MRI scanner due to subject habitus or exceeding weight<br> tolerance limit of the scanner (generally, 350 or 400 lbs, dependent on<br> manufacturer); or<br><br> 3. Claustrophobia: history of severe claustrophobia that would lead to inability<br> to conduct MRI.<br><br> 8. Current acute decompensated HF requiring intravenous (IV) diuretics or recent (<1<br> month before screening) hospitalization for HF.<br><br> 9. Primary cardiomyopathy (e.g., constrictive, restrictive, infiltrative, toxic,<br> hypertrophic [congenital], congenital, or any other primary cardiomyopathy, in the<br> judgement of the Investigator.<br><br> 10. Active myocarditis (COVID-induced or otherwise).<br><br> 11. Active collagen vascular disease.<br><br> 12. Current greater than moderate left- or right sided valve disease, in the opinion of<br> the Investigator.<br><br> 13. Planned cardiac surgery or catheter intervention during the time of trial<br> participation.<br><br> 14. Prior documented EF <40% within the last 3 years.<br><br> 15. Tachycardia (>110 beats/minute) at screening.<br><br> 16. Atrial fibrillation or atrial flutter with an uncontrolled heart rate response or<br> with a resting heart rate greater than 110 bpm by ECG at screening. Subjects may<br> rescreen after appropriate adjustment of medication to manage the atrial<br> fibrillation. A maximum of 16 subjects with this condition can be enrolled in this<br> study.<br><br> 17. Untreated, life-threatening dysrhythmia.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Evaluate weight reduction while on HU6 treatment
- Secondary Outcome Measures
Name Time Method