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

NCT06343298 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ES_MANP_2001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 29

Brief Summary

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.

Conditions

Difficult to Control Hypertension

Keywords

Resistant Hypertension

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• Change in Clinic sitting systolic blood pressure

  Approximately 42 days

• Pharmacokinetics - Cmax

  Approximately 42 days

• Pharmacokinetics - Tmax

  Approximately 42 Days

• Anti-drug Antibody

  Approximately 10 weeks

Other Outcomes (7)

• Differential Outcomes in African-American Subject versus Non-African American Subjects

  Approximately 42 days

• Metabolic biomarkers - Glucose

  Approximately 10 weeks

• Metabolic biomarkers - Insulin

  Approximately 10 weeks

Study Arms (2)

Placebo-matched control

PLACEBO COMPARATOR

Placebo-matched vehicle (vehicle minus the active component)

Other: Placebo Matched control

MANP

ACTIVE COMPARATOR

MANP in vehicle

Drug: MANP

Interventions

MANP DRUG

MANP (modified atrial natriuretic peptide) is a peptide that is being developed for treatment of difficult to control/resistant hypertension.

MANP

Placebo Matched control OTHER

This is a placebo matched vehicle - Vehicle minus the active ingredient

Placebo-matched control

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• E-Star BioTech, LLC: lead
• Mayo Clinic: collaborator
• PPD Development, LP: collaborator

Study Sites (29)

Lynn Institute of the Ozarks

Little Rock, Arkansas, 72204, United States

RECRUITING

Amicis Research Center - Beverly Hills

Beverly Hills, California, 90211, United States

RECRUITING

Amicis Research Center - Granada Hills

Granada Hills, California, 91344, United States

RECRUITING

Orange County Research Center

Lake Forest, California, 92630, United States

RECRUITING

Amicis Research Center - Palmdale

Palmdale, California, 93551, United States

RECRUITING

Amicis Research Site - Valencia

Valencia, California, 91355, United States

RECRUITING

Interventional Cardiology Medical Group

West Hills, California, 91308, United States

WITHDRAWN

Office of Dr. Edward Portnoy MD

Westlake Village, California, 91361, United States

RECRUITING

SM Research Center

Biscayne Park, Florida, 33161, United States

RECRUITING

Arrow Clinical Trials

Daytona Beach, Florida, 32117, United States

RECRUITING

Royal Research Corp

Hollywood, Florida, 33021, United States

RECRUITING

Evolution Clinical Trials

Miami, Florida, 33122, United States

RECRUITING

Cowry Health

Acworth, Georgia, 30101, United States

RECRUITING

Alta Pharmaceutical Research Center

Peachtree Corners, Georgia, 30092, United States

RECRUITING

Cedar Crosse Research Center

Chicago, Illinois, 60607, United States

RECRUITING

Revival Research Institute, LLC

Dearborn, Michigan, 48126, United States

RECRUITING

Aa Mrc Llc

Flint, Michigan, 48504, United States

RECRUITING

Monroe Biomedical Research

Monroe, North Carolina, 28112, United States

RECRUITING

Superior Clinical Research

Smithfield, North Carolina, 27577, United States

RECRUITING

K&R Research LLC

Marion, Ohio, 43302, United States

RECRUITING

Tristar Clinical Investigations, P.C.

Philadelphia, Pennsylvania, 19114, United States

ACTIVE NOT RECRUITING

Prime Research

Coppell, Texas, 75019, United States

ACTIVE NOT RECRUITING

Dallas Renal Group

Dallas, Texas, 75230, United States

RECRUITING

East Texas Cardiology

Houston, Texas, 77002, United States

RECRUITING

Pioneer Research Solutions

Houston, Texas, 77099, United States

RECRUITING

Prime Clinical Research

Mansfield, Texas, 76063, United States

RECRUITING

Clinical Investigations of Texas

Plano, Texas, 75075, United States

RECRUITING

Aavon Clinical Trials

Richmond, Texas, 77407, United States

RECRUITING

Revival Research

Sherman, Texas, 75092, United States

RECRUITING

Study Officials

• David Smith, MD

  E-Star BioTech, LLC

  STUDY DIRECTOR

Central Study Contacts

Seetha R Iyer, MS

CONTACT

212-271-4295; sri@icw.ventures

Lucia Gonzalez

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: April 2, 2024
• Study Start: November 17, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: As needed for publication support
• Access Criteria: IPD will be shared with approved collaborators

Locations

US (29)