Difficult to Control HypertensionPhase 2BOLD-HTNNCT06343298
To Evaluate the Safety and Efficacy of MANP in Subjects With Difficult to Control/ Resistant Hypertension
A Phase 2 study testing MANP in people with Difficult to Control Hypertension, run by E-Star BioTech, LLC at 23 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Difficult to Control Hypertension
- What is being tested?
- MANP
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 23 sitesUnited States
- Study dates
- 17 Nov 2024to 30 Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 2 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 ≥130 mmHg by ABPM prior to randomization (T1).
- Subjects must have a CKD-EPI eGFR ≥ 30 mL/min/1.73m2
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
23 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Lucia Gonzalez contact
23 sites in 1 country
United States23 sites, 22 recruiting
- Recruiting
Cowry Health
Acworth, Georgia, 30101
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Cedar Crosse Research Center
Chicago, Illinois, 60607
BOLD-HTN, bold-HTN@estar.bio
- Active, not recruiting
Prime Research
Coppell, Texas, 75019
- Recruiting
Dallas Renal Group
Dallas, Texas, 75230
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Arrow Clinical Trials
Daytona Beach, Florida, 32117
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Revival Research Institute, LLC
Dearborn, Michigan, 48126
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Revival Research
Denton, Texas, 76210
boldhtn@estar.bio
- Recruiting
Aa Mrc Llc
Flint, Michigan, 48504
Bold-HTN, bold-HTN@estar.bio
- Recruiting
Royal Research Corp
Hollywood, Florida, 33021
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Aavon Clinical research
Houston, Texas, 77074
bold-htn@estar.bio
- Recruiting
Pioneer Research Solutions
Houston, Texas, 77099
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Orange County Research Center
Lake Forest, California, 92630
BOLD-HTN, BSME, bold-HTN@estar.bio
- Recruiting
Lynn Institute of the Ozarks
Little Rock, Arkansas, 72204
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Prime Clinical Research
Mansfield, Texas, 76063
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Evolution Clinical Trials
Miami, Florida, 33122
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Monroe Biomedical Research
Monroe, North Carolina, 28112
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Mt.Sinai
New York, New York, 10029
boldhtn@estar.bio
- Recruiting
Clinical Investigations of Texas
Plano, Texas, 75075
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
Aavon Clinical Trials
Richmond, Texas, 77407
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
SKY CRNG
Ridgeland, Mississippi, 39157
boldhtn@estar.bio
- Recruiting
Revival Research
Sherman, Texas, 75092
BOLD-HTN, bold-HTN@estar.bio
- Recruiting
SKY CRNG
Union City, Georgia, 30291
boldhtn@estar.bio
- Recruiting
Office of Dr. Edward Portnoy MD
Westlake Village, California, 91361
BOLD-HTN, bold-HTN@estar.bio
About this study
Official title: 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.
- Conditions
- Difficult to Control Hypertension
- Being tested
- MANP, Placebo Matched control
- Keywords
- Resistant Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MANPDrug
MANP (modified atrial natriuretic peptide) is a peptide that is being developed for treatment of difficult to control/resistant hypertension.
Placebo Matched controlOther
This is a placebo matched vehicle - Vehicle minus the active ingredient
| Study group | Role | What they receive |
|---|---|---|
| Placebo-matched control | Placebo comparator | Placebo-matched vehicle (vehicle minus the active component) Receives: Other: Placebo Matched control |
| MANP | Active comparator | MANP in vehicle Receives: Drug: MANP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in mean daytime SBP derived from 24-hour ABPM at approximately Day 42.
ABPM
Measured: Approximately 42 days
Incidence and severity of Adverse events through 4- weeks post end of treatment.
Safety
Measured: Approximately 10 weeks
Incidence and severity of Serious Adverse Events through 4- weeks post end of treatment.
Safety
Measured: Approximately 10 weeks
Incidence and severity of Treatment Emergent Adverse Events through 4- weeks post end of treatment.
Safety
Measured: Approximately 10 weeks
Secondary outcomes (4)
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.
Measured: Approximately 42 days
Pharmacokinetics - Cmax
Maximum concentration of MANP in plasma post dose on Day 1 and Last day of Treatment
Measured: 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
Measured: 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
Measured: Approximately 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2024
- Study start17 Nov 2024
- Primary completion1 Jul 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Difficult to Control HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- E-Star BioTech, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Mayo Clinic, PPD Development, LP
- Responsible party
- Sponsor
- Investigators
- David Smith, MD, Study director, E-Star BioTech, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06343298
- Sponsor's protocol ID
- ES_MANP_2001
- Acronym
- BOLD-HTN
- Status last verified
- Sep 2026
- First submitted
- 20 Mar 2024
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that support publications
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06343298
- Acronym / sponsor ID
- BOLD-HTN / ES_MANP_2001
- Conditions
- Difficult to Control Hypertension
- Keywords
- Resistant Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- E-Star BioTech, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Mayo Clinic, PPD Development, LP
- Study start
- 17 Nov 2024 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 2 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo-matched control | Placebo comparator | Other: Placebo Matched controlPlacebo-matched vehicle (vehicle minus the active component) |
| MANP | Active comparator | Drug: MANPMANP in vehicle |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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 2 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 ≥130 mmHg by ABPM prior to randomization (T1).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MANPMANP (modified atrial natriuretic peptide) is a peptide that is being developed for treatment of difficult to control/resistant hypertension. | Drug | MANP |
| Placebo Matched controlThis is a placebo matched vehicle - Vehicle minus the active ingredient | Other | Placebo-matched control |
Primary outcome
Change from baseline in mean daytime SBP derived from 24-hour ABPM at approximately Day 42.
Time frame: Approximately 42 days
ABPM
Incidence and severity of Adverse events through 4- weeks post end of treatment.
Time frame: Approximately 10 weeks
Safety
Incidence and severity of Serious Adverse Events through 4- weeks post end of treatment.
Time frame: Approximately 10 weeks
Safety
Incidence and severity of Treatment Emergent Adverse Events through 4- weeks post end of treatment.
Time frame: Approximately 10 weeks
Safety
4 secondary outcomes
Change in Clinic sitting systolic blood pressure
Time frame: Approximately 42 days
Pharmacokinetics - Cmax
Time frame: Approximately 42 days
Pharmacokinetics - Tmax
Time frame: Approximately 42 Days
Anti-drug Antibody
Time frame: Approximately 10 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Individual participant dataSharing planned: Yes. All IPD that support publications
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lucia Gonzalez contact
David Smith, MD study director
E-Star BioTech, LLC
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MANP in people with Difficult to Control Hypertension, run by E-Star BioTech, LLC at 23 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Seetha R Iyer, MS (212-271-4295, sri@icw.ventures), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in mean daytime SBP derived from 24-hour ABPM at approximately Day 42. (time frame: Approximately 42 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.