Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects

NCT05247528 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ES_MANP_21-01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 5

Brief Summary

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).

Conditions

Resistant Hypertension; Difficult to Control Hypertension

Outcome Measures

Primary Outcomes (28)

• 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 Outcomes (11)

• Cardiac Metrics: Blood pressures

  From Baseline for Day 1-6

• Serum creatinine

  From Baseline for Day 1-6

• MANP

  From baseline for Day 1 & Day 5

• Immune Response

  From baseline for Day 1, Day 5, Day 12, & Day 21

• Metabolics

  From baseline for Day 1 & Day 5

Study Arms (2)

Placebo Comparator

PLACEBO COMPARATOR

* Subjects randomized to the placebo arm, will receive a single subcutaneous injection each morning daily. * Intervention: Placebo

Drug: Placebo

MANP

EXPERIMENTAL

* Subjects randomized to the experimental arm, will receive a single subcutaneous injection each morning daily. (multiple ascending dose cohorts) * Intervention: Drug: MANP

Drug: MANP

Interventions

MANP DRUG

Novel designer peptide to represent a pGC-A/cGMP therapeutic

MANP

Placebo DRUG

Placebo Comparator

Placebo Comparator

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• E-Star BioTech, LLC: lead
• Mayo Clinic: collaborator
• Integrium: collaborator

Study Sites (5)

USA Clinical Site 03

Anniston, Alabama, 36207, United States

Location

USA Clinical Site 01

Tustin, California, 92780, United States

Location

USA Clinical Site 02

DeLand, Florida, 32738, United States

Location

USA Clinical Site 04

Decatur, Georgia, 30030, United States

Location

USA Clinical Site 05

Owensboro, Kentucky, 42303, United States

Location

Study Officials

• Lucia Gonzalez

  E-Star

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: December 22, 2021
• First Posted: February 21, 2022
• Study Start: December 20, 2021
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: November 29, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share

Locations

US (5)