Study of HS135 in Obese Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction

Phase 1b Double-Blind, Placebo-Controlled, MAD Study Assessing the Pharmacokinetics, Safety, Pharmacodynamics, and Efficacy of HS135 in Obese Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction

A Study of HS135 for the Treatment of in Obese Patients with Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction (PH-HFpEF)

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Other: Placebo; Biological: HS135

Detailed Description

Phase 1b, Multicenter, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study Assessing the Pharmacokinetics, Safety, Pharmacodynamics, and Efficacy of HS135 in Obese Patients with Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Site-104
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Site-105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients 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. CardioMEMS™ Heart Failure System implanted during standard of care at least 90 days before Screening.
3. Established diagnosis of HFpEF with Left Ventricular Ejection Fraction (LVEF) at least 45% as measured by echocardiography during Screening.
4. New York Heart Association (NYHA) class II, III or IV heart failure symptoms.
5. BMI ≥ 30 kg/m2.
6. Ability to adhere to study visit schedule and understand and comply with all protocol requirements.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

1. Decompensated heart failure.
2. Admission for an acute coronary syndrome, percutaneous coronary intervention, or cardiac surgery within 30 days prior to Screening.
3. Implantation of cardiac resynchronization therapy (CRT) device within 90 days prior to Screening.
4. Planned cardiovascular revascularization or major cardiac surgery or planned implantation of CRT device.
5. History of heart transplant or on heart transplant list.
6. Uncontrolled systemic hypertension.
7. Patients who have an abnormality in echocardiography or electrocardiogram that in the opinion of the investigator increases the risk of participating in the study.
8. Patients who have full pneumonectomy or a severe chronic pulmonary disorder that in the opinion of the investigator increases the risk of participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subcutaneous Injection	Other: Placebo; Subcutaneous Injection
Experimental: Investigational Product; HS135 Subcutaneous Injection	Biological: HS135; Subcutaneous Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Number of Adverse Events (AEs)	An AE is any untoward medical occurrence in a patient or clinical trial patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The incidence and number of patients who experience an AE will be reported.	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Hematology): White Blood Cell Count	Blood samples will be collected to determine the White Blood Cell Count at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Hematology): Platelet Count	Blood samples will be collected to determine the Platelet Count at designated time points up to 24 weeks.	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Hematology): Red Blood Cell Count	Blood samples will be collected to determine the Red Blood Cell Count at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Hematology): Hemoglobin	Blood samples will be collected to determine concentration of Hemoglobin at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Hematology): Hematocrit	Blood samples will be collected to determine concentration of Hematocrit at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Albumin	Blood samples will be collected to determine concentration of Albumin at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Aspartate aminotransferase (AST)	Blood samples will be collected to determine concentration of AST designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Alanine aminotransferase (ALT)	Blood samples will be collected to determine concentration of ALT designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Alkaline phosphatase (ALP)	Blood samples will be collected to determine concentration of ALP designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Total Bilirubin	Blood samples will be collected to determine concentration of Total Bilirubin at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Calcium	Blood samples will be collected to determine concentration of Calcium at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Creatinine	Blood samples will be collected to determine concentration of Creatinine at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Glucose	Blood samples will be collected to determine concentration of Glucose at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Urea	Blood samples will be collected to determine concentration of Urea at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Total Cholesterol	Blood samples will be collected to determine concentration of Total Cholesterol at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): High-density Lipoprotein-cholesterol (HDL-c)	Blood samples will be collected to determine concentration of HDL-c at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Low-density Lipoprotein-cholesterol (LDL-c)	Blood samples will be collected to determine concentration of LDL-c at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Chloride	Blood samples will be collected to determine concentration of Chloride at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Potassium	Blood samples will be collected to determine concentration of Potassium at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Biochemistry): Sodium	Blood samples will be collected to determine concentration of Sodium at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): Blood (occult)	Urine samples will be collected to determine the presence of Blood (occult) at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): Ketones	Urine samples will be collected to determine the presence of Ketones at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): Leukocyte Esterase	Urine samples will be collected to determine the presence Leukocyte Esterase of at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): Nitrites	Urine samples will be collected to determine the presence of Nitrites at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): Bilirubin	Urine samples will be collected to determine the presence of Bilirubin at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): Glucose	Urine samples will be collected to determine the presence of Glucose at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): Urobilinogen	Urine samples will be collected to determine concentration of Urobilinogen at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): Protein	Urine samples will be collected to determine the presence of Protein at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): pH	Urine samples will be collected to determine the pH at designated time points up to 24 weeks	Up to 24 weeks
Change from Baseline in Clinical Laboratory Parameters (Urinalysis): Specific Gravity	Urine samples will be collected to determine the Specific Gravity at designated time points up to 24 weeks	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in mean pulmonary artery diastolic pressure (mPADP) at designated time points up to 24 weeks	To determine mean pulmonary artery diastolic pressure (mPADP)	Up to 24 weeks
Change from Baseline in mean pulmonary artery pressure (mPAP) at designated time points up to 24 weeks	To determine mean pulmonary artery pressure (mPAP)	Up to 24 weeks
Change from Baseline in mean pulmonary artery systolic pressure (mPASP) at designated time points up to 24 weeks	To determine mean pulmonary artery systolic pressure (mPASP)	Up to 24 weeks
Change in New York Heart Association (NYHA) Class at designated time points up to 24 weeks	To determine change in New York Heart Association (NYHA) Class at Week 24	Up to 24 weeks
Change from Baseline in number of hospitalizations or urgent outpatient visits for heart failure during the treatment period at designated time points at designated time points up to 24 weeks	To determine number of hospitalizations or urgent outpatient visits for heart failure during the treatment period	Up to 24 weeks
Change from Baseline to Week 24 in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at designated time points up to 24 weeks	To determine N-terminal pro-B-type natriuretic peptide (NT-proBNP)	Up to 24 weeks
Change from Baseline in 6-minute walk distance (6MWD) at designated time points up to 24 weeks	To determine 6-minute walk distance (6MWD)	Up to 24 weeks
Change from Baseline in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CS) and Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OS) at designated time points up to 24 weeks	To determine change from Baseline in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CS) and Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OS) at Week 24.	Up to 24 weeks

Collaborators and Investigators

• Sponsor: 35Pharma Inc
• Investigators: Study Director: Monique Champagne, M.Sc., 35Pharma Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2025
• Primary Completion (Actual): July 29, 2025
• Study Completion (Actual): July 29, 2025

Study Registration Dates

• First Submitted: August 9, 2024
• First Submitted That Met QC Criteria: August 29, 2024
• First Posted (Actual): September 3, 2024

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: HS135-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No