Single-Ascending Dose Study of JK07 in Subjects With HFpEF

NCT05322616 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: JK07.1.02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 7

Brief Summary

A phase 1, randomized, double-blind, placebo-controlled single-ascending dose study to assess JK07 in adult subjects with heart failure with preserved ejection fraction.

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

heart failure; HFpHF; neuregulin-1

Outcome Measures

Primary Outcomes (1)

• Safety Assessment

  Incidence and severity of treatment-emergent adverse events (safety and tolerability) by assessment of physical exams, injection site, vital signs and clinical laboratory tests.

  Screening to Day 28

Other Outcomes (4)

• Natriuretic peptide

  Screening to Day 180

• Quality of Life - Kansas City Cardiomyopathy Questionnaire (KCCQ)

  Screening to Day 180

• 6-Minute Walking Test (6MWT)

  Screening to Day 180

Study Arms (2)

JK07

ACTIVE COMPARATOR

Single dose of intravenous JK07 administered by intravenous infusion over 60 minutes.

Drug: JK07

Matching Placebo

PLACEBO COMPARATOR

Single dose of vehicle control administered by intravenous infusion over 60 minutes

Drug: Matching Placebo

Interventions

JK07 DRUG

Recombinant fusion protein consisting of a fully humanized immunoglobulin G1 monoclonal antibody and an active polypeptide fragment of the human growth factor NRG-1

JK07

Matching Placebo DRUG

Vehicle control

Matching Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stable New Yok Heart Association (NYHA) Class II or III HF diagnosis, evident at least 6 months prior to enrollment as confirmed by medical history.
• Documented prior objective evidence of heart failure as shown by 1 or more of the following criteria:
• Previous hospitalization for heart failure with documented radiographic evidence of pulmonary congestion.
• Elevated left ventricular (LV) end-diastolic pressure or pulmonary capillary wedge pressure at rest (≥15 mm Hg) or with exercise (≥25 mm Hg).
• Elevated level of NT-proBNP (\>400 pg/mL) or brain natriuretic peptide (BNP) (\>200 pg/mL).
• Echocardiographic evidence of medial E/e' ratio ≥ 15 or Left Atrial Volume (LAV) \>58 mL in male patients or \>52 mL in female patients.
• Adequate acoustic windows on screening resting TTE
• Documented structural abnormality consistent with HFpEF confirmed at the screening visit by clearly interpretable echocardiography assessment.
• Meets 1 or more of the following criteria at the initial screening measurement:
• A hs-cTnI \>99th percentile
• NT-proBNP \>300 pg/mL (if not in atrial fibrillation or atrial flutter) or \>600 pg/mL (if in atrial fibrillation or atrial flutter), or if the screened participant is either of African descent or has a body mass index ≥30.0 kg/m2, a screening NT-proBNP \>240 pg/mL (if not in atrial fibrillation or atrial flutter) or \>480 pg/mL (if in atrial fibrillation or atrial flutter).
• Body mass index (BMI) ≥18 kg/m2 and ≤45 kg/m2
• Screening hemoglobin ≥9.0 g/dL, platelets ≥100x109 /mL, absolute neutrophil count (ANC) ≥1500/mL.
• Sexually mature biological male subjects must agree to use a medically accepted method of contraception throughout the study and be willing and able to continue contraception until the end of the study (6-month time point).
• Biological females of childbearing potential must present with a negative blood pregnancy test, must not be lactating, and must agree to employ adequate birth control measures for the duration of the study and be willing and able to continue contraception until the end of the study (6-month time point).

You may not qualify if:

• Cardiac-Related
• Participating in any other study and have received any other investigational drug within 30 days prior to screening or 5-half-lives, whichever is longer, or any other investigational implanted device within 30 days prior to screening, or are taking part in a nonmedication study which, in the opinion of the Investigator, would interfere with study compliance or outcome assessments.
• Any past participation in a study that has investigated the NRG-1 pathway (e.g., Neucardin, cimaglermin).
• Has a prior diagnosis of hypertrophic cardiomyopathy or a known infiltrative or storage disorder causing HFpEF and/or cardiac hypertrophy, such as amyloidosis, Fabry disease, or Noonan syndrome with LV hypertrophy or a positive serum immunofixation result.
• Has a history of syncope within the last 6 months or sustained ventricular tachycardia with exercise within the past 6 months.
• Has persistent or permanent atrial fibrillation and is not therapeutically anticoagulated for at least the 4 weeks prior to the initial screening visit or is not adequately rate controlled within 6 months prior to informed consent according to investigator discretion.
• Has known moderate or severe aortic valve stenosis, hemodynamically significant mitral stenosis, or severe mitral or tricuspid regurgitation at informed consent.
• Has severe chronic obstructive pulmonary disease, or other severe pulmonary disease, requiring home oxygen, chronic nebulizer therapy, chronic oral steroid therapy or hospitalized for pulmonary decompensation within 12 months of informed consent.
• Diagnosed with medically documented acute coronary syndrome within 3 months of screening or a medically documented acute myocardial infarction within 6 months of screening.
• Cardiac surgery, coronary artery revascularization, percutaneous coronary intervention, or valvuloplasty within 3 months prior to screening.
• Any subject who has received an indication for coronary revascularization within 3 months prior to screening.
• Any of the following confirmed by duplicate seated determinations on at least 3 consecutive readings (in clinic/office) following informed consent and prior to randomization:
• Systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) \>100 mmHg
• Sustained SBP \<90 mmHg and/or DBP \<40 mmHg and/or symptomatic hypotension
• Sustained resting heart rate (HR) \<50 or ≥100 bpm or \>110 bpm if chronic AF at Screening (Visit 1) or prior to randomization for \>15 minutes in two episodes separated by one hour of observation

Sponsors & Collaborators

• Salubris Biotherapeutics Inc: lead

Study Sites (7)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Harvard Medical School/Massachusetts General Hospital

Boston, Massachusetts, 02114-2696, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health and Science University Hospital

Portland, Oregon, 97239, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Heart Failure; Fibromatosis, Gingival, 2

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Wilson Tang, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matched placebo-solution
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled, Single- Ascending Dose

Study Record Dates

• First Submitted: March 14, 2022
• First Posted: April 12, 2022
• Study Start: October 21, 2022
• Primary Completion: May 26, 2023
• Study Completion: May 26, 2023
• Last Updated: May 31, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)