HS235 Study in Obese Participants With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (HFpEF)

35Pharma Inc

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Heart Failure With Preserved Ejection Fraction; Pulmonary Hypertension

Treatments: Other: Placebo; Biological: HS235

Study type: Interventional

Funder types: Industry

Identifiers

NCT07123779

HS235-003

Details and patient eligibility

About

Study of HS235 in Obese Participants with Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction

Full description

A Phase 1b/2, Multicenter, Double-Blind, Placebo-Controlled, Multiple Dose Study Assessing the Pharmacokinetics, Safety, Pharmacodynamics, and Efficacy of HS235 in Obese Participants with Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction

Enrollment: 126 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants are eligible to be included in the study only if they meet at least all the following criteria:

1. Male or female, ≥ 18 years of age.

2. [Sub-population A only - using a remote PAP sensor]- Ambulatory PAP monitoring (e.g., CardioMEMS™ HF System or Cordella™ HF System) implanted in the course of standard of care at least 90 days before Screening.

   Hemodynamic evidence of PH with:

   1. mPAP ≥ 25 mm Hg, as measured in supine position by the averaged 7-day values (weekly average) 2 weeks and 1 week before Randomization AND,
   2. dPAP ≥ 15 mm Hg, as measured in supine position by the averaged 7-day values (weekly average) 2 weeks and 1 week before Randomization.

3. [Sub-population B only - without a remote PAP sensor]

   Hemodynamic evidence of PH based on the presence of all the following RHC parameters obtained during the Screening period, prior to randomization:

   1. PVR ≥ 240 dyn*sec/cm5 or ≥ 3 WU, and
   2. mPAP > 20 mmHg, and
   3. PAWP > 15 mmHg but < 30 mmHg, and
   4. dPAP ≥ 15 mmHg.

4. Established diagnosis of HFpEF with left ventricular ejection fraction (LVEF) ≥ 45 % as measured by echocardiography during Screening and and no documented LVEF < 45% during the 2 years preceding Screening..

5. New York Heart Association (NYHA) class II or III heart failure symptoms.

6. Stable diuretic regimen during the screening period.

7. Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) < 90 at screening.

8. 6-minute walking distance (6MWD) ≥ 100 m at screening.

9. Body mass index ≥ 30 to ≤ 50 kg/m2 and Body weight ≤140 kg.

10. Ability to adhere to study visit schedule and understand and comply with all protocol requirements.

Exclusion criteria

1. Hospitalization for any worsening medical condition or major surgery within 4 weeks prior to screening.
2. Occurrence of an acute coronary syndrome, percutaneous coronary intervention, or cardiac surgery within 90 days prior to Screening.
3. Implantation of a cardiac resynchronization therapy (CRT) device within 90 days before screening.
4. Planned cardiovascular revascularization or planned implantation of CRT device.
5. History of heart transplant or on heart transplant list.
6. History of serious or life-threatening cardiac arrhythmia within 90 days prior to screening.
7. Systemic hypotension or uncontrolled systemic hypertension.
8. History of Pericardial constriction or hypertrophic cardiomyopathy.
9. History of significant valvular stenosis or regurgitation.
10. Participants with a pneumonectomy or more than moderate Chronic Obstructive Pulmonary Disease (COPD) or mild interstitial lung disease (ILD) or mild obstructive sleep apnea (OSA).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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126 participants in 2 patient groups, including a placebo group

Investigational Product

Experimental group

Description:

HS235 Subcutaneous Injection

Treatment:

Biological: HS235

Placebo

Placebo Comparator group

Description:

Subcutaneous Injection

Treatment:

Other: Placebo