To Evaluate the Safety and Efficacy of MANP in Subjects With Difficult to Control/ Resistant Hypertension (BOLD-HTN)

October 2, 2025 updated by: E-Star BioTech, LLC

A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE TITRATION, MULTI-CENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF SUBCUTANEOUS MANP WHEN ADMINISTERED ONCE DAILY FOR 42 DAYS IN PARTICIPANTS 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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Lucia Gonzalez

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72204
    • California
      • Beverly Hills, California, United States, 90211
        • Recruiting
        • Amicis Research Center - Beverly Hills
        • Contact:
      • Granada Hills, California, United States, 91344
        • Recruiting
        • Amicis Research Center - Granada Hills
        • Contact:
      • Lake Forest, California, United States, 92630
        • Recruiting
        • Orange County Research Center
        • Contact:
      • Palmdale, California, United States, 93551
        • Recruiting
        • Amicis Research Center - Palmdale
        • Contact:
      • Valencia, California, United States, 91355
      • West Hills, California, United States, 91308
        • Withdrawn
        • Interventional Cardiology Medical Group
      • Westlake Village, California, United States, 91361
    • Florida
      • Biscayne Park, Florida, United States, 33161
      • Daytona Beach, Florida, United States, 32117
      • Hollywood, Florida, United States, 33021
      • Miami, Florida, United States, 33122
    • Georgia
      • Acworth, Georgia, United States, 30101
      • Peachtree Corners, Georgia, United States, 30092
        • Recruiting
        • Alta Pharmaceutical Research Center
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60607
    • Michigan
      • Dearborn, Michigan, United States, 48126
      • Flint, Michigan, United States, 48504
    • North Carolina
      • Monroe, North Carolina, United States, 28112
      • Smithfield, North Carolina, United States, 27577
    • Ohio
      • Marion, Ohio, United States, 43302
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19114
        • Active, not recruiting
        • Tristar Clinical Investigations, P.C.
    • Texas
      • Coppell, Texas, United States, 75019
        • Active, not recruiting
        • Prime Research
      • Dallas, Texas, United States, 75230
      • Houston, Texas, United States, 77099
      • Houston, Texas, United States, 77002
      • Mansfield, Texas, United States, 76063
      • Plano, Texas, United States, 75075
      • Richmond, Texas, United States, 77407
      • Sherman, Texas, United States, 75092

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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.
Time Frame: Approximately 42 days
ABPM
Approximately 42 days
Incidence and severity of Adverse events through 4- weeks post end of treatment.
Time Frame: Approximately 10 weeks
Safety
Approximately 10 weeks
Incidence and severity of Serious Adverse Events through 4- weeks post end of treatment.
Time Frame: Approximately 10 weeks
Safety
Approximately 10 weeks
Incidence and severity of Treatment Emergent Adverse Events through 4- weeks post end of treatment.
Time Frame: Approximately 10 weeks
Safety
Approximately 10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Clinic sitting systolic blood pressure
Time Frame: Approximately 42 days
Achieving mean seated (5 minutes) systolic blood pressure blood pressure control ≤ 130 mmHg at end of treatment visit.
Approximately 42 days
Pharmacokinetics - Cmax
Time Frame: Approximately 42 days
Maximum concentration of MANP in plasma post dose on Day 1 and Last day of Treatment
Approximately 42 days
Pharmacokinetics - Tmax
Time Frame: Approximately 42 Days
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
Time Frame: Approximately 10 weeks
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
Time Frame: Approximately 42 days
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
Time Frame: Approximately 10 weeks
Change from baseline in plasma Glucose at end of treatment and Follow-up
Approximately 10 weeks
Metabolic biomarkers - Insulin
Time Frame: Approximately 10 weeks
Change from baseline in plasma Insulin at end of treatment and Follow-up
Approximately 10 weeks
Metabolic biomarkers - HbA1C
Time Frame: Approximately 10 weeks
Change from baseline in HbA1C at end of treatment and Follow-up
Approximately 10 weeks
Lipid biomarkers - HDL
Time Frame: Approximately 10 weeks
Change from baseline in plasma High density Lipoprotein (HDL) at end of treatment and Follow-up
Approximately 10 weeks
Lipid biomarkers - LDL
Time Frame: Approximately 10 weeks
Change from baseline in plasma Low density Lipoprotein (LDL) at end of treatment and Follow-up
Approximately 10 weeks
Lipid biomarkers - TG
Time Frame: Approximately 10 weeks
Change from baseline in plasma Triglycerides (TG) at end of treatment and Follow-up
Approximately 10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

E-Star BioTech, LLC

Collaborators

Mayo Clinic
PPD Development, LP

Investigators

  • Study Director: David Smith, MD, E-Star BioTech, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 17, 2024

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

September 1, 2026

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 (Estimated)

October 6, 2025

Last Update Submitted That Met QC Criteria

October 2, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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