Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects (DTC/RHS)

A Phase 1B, Multiple Ascending Dose Trial Examining The Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects

A randomized, double-blind, placebo-controlled multiple ascending dose study in hypertensive subjects on stable doses of at least three hypertensive drugs for at least 6 weeks prior to Screening. The study will consist of screening, PK-unit admittance, and safety follow up periods.

Subjects will be randomized at a 6:2 ratio of either MANP or placebo and will be stratified by race in each dosage cohort. The entire first Cohort will be given the lowest dosage with subsequent cohorts progressing sequentially to the higher doses depending on safety and tolerability of the previous cohort.

Endpoints not related to the safety reviews will be analyzed after the last patient last visit (LPLV).

Study Overview

• Status: Completed
• Conditions: Resistant Hypertension; Difficult to Control Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: MANP

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • USA Clinical Site 03
  • California
    • Tustin, California, United States, 92780
      • USA Clinical Site 01
  • Florida
    • DeLand, Florida, United States, 32738
      • USA Clinical Site 02
  • Georgia
    • Decatur, Georgia, United States, 30030
      • USA Clinical Site 04
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • USA Clinical Site 05

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• DTC/RH diagnosed with clinic SBP ≥140 mmHg or DBP ≥ 90 mmHg (or SBP ≥ 130 mmHg or DBP ≥ 80 mmHg for diabetics) while on at least three standard-of-care antihypertensive medications (which must include a diuretic).
• MDRD eGFR ≥ 30 mL/min.
• Men and women between the ages of 18 - 80.
• BMI within the range of 18-40 kg/m2.
• Women of childbearing potential must not be pregnant and agree to avoid becoming pregnant while receiving study treatment and for 14 days after the last study visit.

Exclusion Criteria:

• HbA1c ≥ 8% at Screening.
• Use of other investigational drugs within 30 days of screening or foreseen use during the study.
• Inability to comply with study requirements as judged by the Investigator.
• Pregnant and/or breastfeeding.
• Any disease or condition (medical or surgical) which, in the opinion of the investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk.

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 Comparator; Subjects randomized to the placebo arm, will receive a single subcutaneous injection each morning daily.; Intervention: Placebo	Drug: Placebo; Placebo Comparator
Experimental: MANP; Subjects randomized to the experimental arm, will receive a single subcutaneous injection each morning daily. (multiple ascending dose cohorts); Intervention: Drug: MANP	Drug: MANP; Novel designer peptide to represent a pGC-A/cGMP therapeutic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number and percent of participants with one or more Treatment Emergent Adverse Events (TEAEs) or any serious adverse events (SAEs).	through study completion, an average of 2 months.
Blood Pressure	Change in SBP and DBP	From baseline to Days 1-6, Day 12, and 21.
Hematology Hematocrit	Change in Percent Hematocrit	From baseline to Day 21.
Physical Examination: Body Parts	Change in investigator assessment of the condition of body parts (head, throat, abdomen, and extremities)	From baseline to Day 21
ECG: QT interval	Change in 12-Lead ECG QT Interval	From baseline to Days 1-6 and Day 21.
Temperature	Change in Temperature	From baseline to Days 1-6, Day 12, and 21.
Pulse Rate	Change in Pulse Rate	From baseline to Days 1-6, Day 12, and 21.
Hematology: Hemoglobin	Change in g/dL Hemoglobin	From baseline to Day 21
Hematology: Mean Corpuscular Hemoglobin	Change in the mean corpuscular hemoglobin.	From baseline to Day 21
Hematology: Platelets	Change in platelet count	From baseline to Day 21
Hematology: RBC distribution	Change in red blood cell distribution width	From baseline to Day 21
Hematology: RBC	Change in red blood cell count	From baseline to Day 21
Hematology: WBC	Change in white blood cell count	From baseline to Day 21
Chemistry: Sodium	Change in Sodium concentration.	From baseline to Day 21
Chemistry: Potassium	Change in Potassium concentration.	From baseline to Day 21
Chemistry: Chloride	Change in Chloride concentration	From baseline to Day 21
Chemistry: Bicarbonate	Change in Bicarbonate concentration	From baseline to Day 21
Chemistry: Alanine aminotransferase	Change in ALT (IU/L)	From baseline to Day 21
Chemistry: Aspartate aminotransferase	Change in AST (IU/L)	From baseline to Day 21
Chemistry: Alkaline phosphatase	Change in Alkaline phosphatase (IU/L)	From baseline to Day 21
Chemistry: Bilirubin	Change in Total bilirubin (mg/dL)	From baseline to Day 21
Chemistry: Blood urea nitrogen	Change in BUN (mg/dL)	From baseline to Day 21
Chemistry: Creatinine	Change in Creatinine (mg/dL)	From baseline to Day 21
Chemistry: Glucose	Change in Glucose (mg/dL)	From baseline to Day 21
Chemistry: HbA1c	Change in percent HbA1c	From baseline to Day 21
Physical Examination: Organs	Change in investigator assessment of the condition of organs (skin, eyes, ears, nose, thyroid, lungs, liver, spleen, and lymph nodes)	From baseline to Day 21
Abbreviated Neurological Examination	Change in investigator assessment of neurological condition	From baseline to Day 21
ECG: QTc interval	Change in 12-Lead ECG QTc (Fridericia's) Interval	From baseline to Days 1-6 and Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Metrics: Blood pressures	Change in SBP and DBP	From Baseline for Day 1-6
Serum creatinine	Change in Serum creatinine	From Baseline for Day 1-6
MANP	Change in amount of Plasma MANP both in plasma.	From baseline for Day 1 & Day 5
Immune Response	Change in amount of anti-MANP and anti-ANP	From baseline for Day 1, Day 5, Day 12, & Day 21
Metabolics	Change in amount of non-esterified insulin and glucose.	From baseline for Day 1 & Day 5
eGFR,	Change in eGFR,	From Baseline for Day 1-6
Urine flow rate	Change in urine flow rate	From Baseline for Day 1-6
Urinary Sodium Excretion	Change in amount of urinary sodium excretion	From Baseline for Day 1-6
cGMP	Change in amount of cGMP both in plasma and urine	from baseline for Day 1 & Day 5
Aldosterone	Change in amount of aldosterone both in plasma and urine	from baseline for Day 1 & Day 5
Cardiac Metrics:	Heart Rate	From Baseline for Day 1-6

Collaborators and Investigators

• Sponsor: E-Star BioTech, LLC
• Collaborators: Mayo Clinic; Integrium
• Investigators: Study Director: Lucia Gonzalez, E-Star

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2021
• Primary Completion (Actual): October 31, 2022
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: ES_MANP_21-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All IPD that underlie results in a publication

Drug and device information, study documents

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