To Evaluate the Safety and Efficacy of MANP in Subjects With Difficult to Control/ Resistant Hypertension

A Phase 2 Double-blind, Placebo-Controlled Dose Titration Study to Evaluate the Safety and Efficacy of SQ MANP When Administered Daily for Approximately 42 Days in Subjects With Difficult to Control Hypertension/ Resistant Hypertension

This is a Phase 2 dose-titration study designed to evaluate the safety and efficacy of MANP subcutaneous injection compared to placebo in reducing baseline daytime systolic blood pressure (SBP), derived from 24-hour ambulatory blood pressure monitoring (ABPM), in subjects with hypertension who are taking 3 or more antihypertensive medications with different mechanisms of action.

Study Overview

• Status: Not yet recruiting
• Conditions: Difficult to Control Hypertension
• Intervention / Treatment: Other: Placebo Matched control; Drug: MANP

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Seetha R Iyer, MS; Phone Number: 212-271-4295; Email: sri@icw.ventures
• Study Contact Backup: Name: Lucia Gonzalez

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Subjects will be eligible for enrollment in the study only if they meet ALL the following criteria at time of Screening:

• Male or female subjects aged 18 - 80 years, inclusive, at the screening visit.
• Female subjects must not be of childbearing potential
• Subjects must be taking appropriate doses of 3 or more antihypertensive drugs with different mechanisms of action. One of which must be a diuretic and the other must be an ACEi or ARB at atleast 50% of the maximum recommended dose for hypertension.
• Subjects must have a seated (5 minutes) systolic blood pressure ≥ 140 mmHg and SBP ≥135 mmHg by ABPM prior to randomization (T1).
• Subjects must have a CKD-EPI eGFR ≥ 30 mL/min/1.73m2
• A subset of the subjects with an eGFR between 20-30 ml/min/1.73m2 will be included, not to exceed 10% of the total study subjects.
• Subjects must have a BMI between 18 - 40 kg/m2.
• Subjects who engage in sexual intercourse in which their partner could become pregnant must agree to use a barrier method of birth control (i.e., vaginal/penile condom) with spermicide for the duration of the study and for 90 days after the last dose of study drug or be at least 6 weeks post-vasectomy with confirmation by post-vasectomy semen analysis. In addition, subjects may not donate sperm for the duration of the study and for 90 days after the last dose of study drug.

Exclusion Criteria:

Subjects meeting ANY of the following criteria at time of Screening will be excluded from enrollment:

• Subjects with an average sitting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥ 110 mmHg at Screening (SV), or prior to randomization at T1.
• Subjects with a history of secondary hypertension, including but not limited to coarctation of the aorta, primary hyperaldosteronism, renal artery stenosis, Cushing's disease, pheochromocytoma, and polycystic kidney disease. If the subject has not previously been evaluated for secondary hypertension, investigators are responsible for evaluating all potential secondary causes of hypertension in accordance with current practices and clinical guidelines before entering the patient into the study.
• Subjects with an HbA1c ≥ 8% at screening (SV)
• Subjects who have experienced myocardial infarction, unstable angina, or a cerebrovascular accident (CVA) within 6 months of the Screening Visit; or sick sinus syndrome or second- or third-degree atrioventricular block, or recurrent atrial tachyarrhythmia, recurrent ventricular tachycardia, or symptomatic bradycardia.
• Subjects who have an implanted cardioverter defibrillator (ICD) that has been fired for any arrhythmia within 3 months of Screening (SV) or implanted pacemakers.
• Subjects with congestive heart failure (New York Heart Association [NYHA] class II-IV)
• Subjects with hemodynamically significant valvular heart disease
• Subjects undergoing hemodialysis or peritoneal dialysis, or history of renal transplant.
• Subjects who have diagnosis or recurrence of malignancy within the past 3 years
• Subjects with a documented history of sleep apnea, with a prescription for CPAP therapy.
• Women of childbearing potential
• Subjects who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo-matched control; Placebo-matched vehicle (vehicle minus the active component)	Other: Placebo Matched control; This is a placebo matched vehicle - Vehicle minus the active ingredient
Active Comparator: MANP; MANP in vehicle	Drug: MANP; MANP (modified atrial natriuretic peptide) is a peptide that is being developed for treatment of difficult to control/resistant hypertension.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean daytime SBP derived from 24-hour ABPM at approximately Day 42.	ABPM	Approximately 42 days
Incidence and severity of Adverse events through 4- weeks post end of treatment.	Safety	Approximately 10 weeks
Incidence and severity of Serious Adverse Events through 4- weeks post end of treatment.	Safety	Approximately 10 weeks
Incidence and severity of Treatment Emergent Adverse Events through 4- weeks post end of treatment.	Safety	Approximately 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinic sitting systolic blood pressure	Achieving mean seated (5 minutes) systolic blood pressure blood pressure control ≤ 130 mmHg at end of treatment visit.	Approximately 42 days
Pharmacokinetics - Cmax	Maximum concentration of MANP in plasma post dose on Day 1 and Last day of Treatment	Approximately 42 days
Pharmacokinetics - Tmax	Time required to achieve maximum concentration of MANP in plasma post dose on Day 1 and Last day of Treatment	Approximately 42 Days
Anti-drug Antibody	Change in Anti-drug antibodies against MANP and ANP at Days 21 and 42 post treatment and at follow up visits 1 and 2 compared to baseline	Approximately 10 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential Outcomes in African-American Subject versus Non-African American Subjects	Change mean daytime SBP from ABPM, from baseline compared to end of treatment visit in African American population and the non-African American population at each dose level.	Approximately 42 days
Metabolic biomarkers - Glucose	Change from baseline in plasma Glucose at end of treatment and Follow-up	Approximately 10 weeks
Metabolic biomarkers - Insulin	Change from baseline in plasma Insulin at end of treatment and Follow-up	Approximately 10 weeks
Metabolic biomarkers - HbA1C	Change from baseline in HbA1C at end of treatment and Follow-up	Approximately 10 weeks
Lipid biomarkers - HDL	Change from baseline in plasma High density Lipoprotein (HDL) at end of treatment and Follow-up	Approximately 10 weeks
Lipid biomarkers - LDL	Change from baseline in plasma Low density Lipoprotein (LDL) at end of treatment and Follow-up	Approximately 10 weeks
Lipid biomarkers - TG	Change from baseline in plasma Triglycerides (TG) at end of treatment and Follow-up	Approximately 10 weeks

Collaborators and Investigators

• Sponsor: E-Star BioTech, LLC
• Collaborators: Mayo Clinic; PPD
• Investigators: Principal Investigator: George Bakris, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Resistant Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: ES_MANP_2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that support publications
• IPD Sharing Time Frame: As needed for publication support
• IPD Sharing Access Criteria: IPD will be shared with approved collaborators
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No