Clinical trial NCT06343298: To Evaluate the Safety and Efficacy of MANP in Subjects With Difficult to Control/ Resistant Hypertension
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Difficult to Control Hypertension
Keywords: Resistant Hypertension
Lead sponsor: E-Star BioTech, LLC
Sponsor class: INDUSTRY
Collaborators: name: Mayo Clinic
name: PPD Development, LP
First posted: 2024-04-02
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in mean daytime SBP derived from 24-hour ABPM at approximately Day 42.
timeFrame: Approximately 42 days
measure: Incidence and severity of Adverse events through 4- weeks post end of treatment.
timeFrame: Approximately 10 weeks
measure: Incidence and severity of Serious Adverse Events through 4- weeks post end of treatment.
timeFrame: Approximately 10 weeks
measure: Incidence and severity of Treatment Emergent Adverse Events through 4- weeks post end of treatment.
timeFrame: Approximately 10 weeks
Secondary outcomes:
measure: Change in Clinic sitting systolic blood pressure
timeFrame: Approximately 42 days
measure: Pharmacokinetics - Cmax
timeFrame: Approximately 42 days
measure: Pharmacokinetics - Tmax
timeFrame: Approximately 42 Days
measure: Anti-drug Antibody
timeFrame: Approximately 10 weeks
Other outcomes:
measure: Differential Outcomes in African-American Subject versus Non-African American Subjects
timeFrame: Approximately 42 days
measure: Metabolic biomarkers - Glucose
timeFrame: Approximately 10 weeks
measure: Metabolic biomarkers - Insulin
timeFrame: Approximately 10 weeks
measure: Metabolic biomarkers - HbA1C
timeFrame: Approximately 10 weeks
measure: Lipid biomarkers - HDL
timeFrame: Approximately 10 weeks
measure: Lipid biomarkers - LDL
timeFrame: Approximately 10 weeks
measure: Lipid biomarkers - TG
timeFrame: Approximately 10 weeks
Locations:
city: Beverly Hills
country: United States
facility: Amicis Research Center - Beverly Hills
state: California
city: Granada Hills
country: United States
facility: Amicis Research Center - Granada Hills
state: California
city: Lake Forest
country: United States
facility: Orange County Research Center
state: California
city: Palmdale
country: United States
facility: Amicis Research Center - Palmdale
state: California
city: Valencia
country: United States
facility: Amicis Research Site - Valencia
state: California
city: West Hills
country: United States
facility: Interventional Cardiology Medical Group
state: California
city: Westlake Village
country: United States
facility: Office of Dr. Edward Portnoy MD
state: California
city: Daytona Beach
country: United States
facility: Arrow Clinical Trials
state: Florida
city: Hollywood
country: United States
facility: Royal Research Corp
state: Florida
city: Miami
country: United States
facility: Evolution Clinical Trials
state: Florida
city: Peachtree Corners
country: United States
facility: Alta Pharmaceutical Research Center
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Dearborn
country: United States
facility: Revival Research Institute, LLC
state: Michigan
city: Flint
country: United States
facility: Aa Mrc Llc
state: Michigan
city: Monroe
country: United States
facility: Monroe Biomedical Research
state: North Carolina
city: Marion
country: United States
facility: K&R Research LLC
state: Ohio
city: Philadelphia
country: United States
facility: Tristar Clinical Investigations, P.C.
state: Pennsylvania
city: Coppell
country: United States
facility: Prime Revival Research
state: Texas
city: Houston
country: United States
facility: East Texas Cardiology
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Sherman
country: United States
facility: Revival Research
state: Texas
Study officials:
affiliation: E-Star BioTech, LLC
name: David Smith, MD
role: STUDY_DIRECTOR
References: