Study of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF)

NCT04210375 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: JK07.1.01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 7

Brief Summary

This is a Phase 1, randomized, double-blind, placebo-controlled, single-ascending dose study to assess the safety, tolerability, immunogenicity, PK, and exploratory efficacy of JK07 in subjects 18 to 80 years of age with HFrEF ≤40%. Initially 5 cohorts are planned with the option to expand the study to a total of 7 cohorts. The size of the cohorts will range from 5 to 9 subjects. Each cohort will include one single active unblinded sentinel subject receiving a single IV dose of JK07 prior to randomized single dose administration of JK07 or placebo \[3:1\] in the remainder of the cohort.

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

heart failure; HFrEF; neuregulin 1; NRG-1; heregulin; HER3; HER4; ErbB3; ErbB4; reduced ejection fraction

Outcome Measures

Primary Outcomes (1)

• Incidence and Severity of Treatment-emergent Adverse Events [Safety and Tolerability]

  All safety information is collected and evaluated.

  Screening to 30 days

Secondary Outcomes (3)

• AUC(0-last) of JK07

  Baseline to 60 days

• Cmax of JK07

  Baseline to 60 days

• t1/2 of JK07

  Baseline to 60 days

Other Outcomes (1)

• Left Ventricular Ejection Fraction (LVEF)

  Screening to 180 days

Study Arms (2)

JK07

ACTIVE COMPARATOR

Single dose of JK07 administered by intravenous infusion over 60 minutes

Drug: JK07

Matching Placebo

PLACEBO COMPARATOR

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

You may qualify if:

• Adults 18 and 80 years with stable NYHA Class II or III HF diagnosis (ischemic or non-ischemic confirmed by medical history) at least 6 months prior to enrollment as confirmed by medical history.
• Stable HF defined as no hospitalizations for cardiac-related issues within the previous 2 months prior to the screening visit or between screening and randomization, other than for routine percutaneous procedures such as device, battery, generator changes or pacemaker lead insertion/ replacement.
• Subjects with clearly interpretable echocardiographic images and with a screening LVEF ≤ 40% in the absence of ≥ Grade 3 valvular disease on 2D-TTE.
• Subjects must be taking clinician-directed appropriate pharmacological therapy for HF as per the 2017 ACC/AHA/HFSA treatment guidelines at stable doses and at investigator determined discretion (except for diuretics) for at least 2 months prior to informed consent.
• Subjects with implantable cardioverter-defibrillators (ICDs) are allowed at the discretion of the investigator, but only if both the following criteria are met: (a) paced beats cannot exceed 15% of beats as quantified by screening e-Patch, and (b) if a non-paced baseline ECG can be obtained on day 1 prior to study drug administration.
• \. Body mass index ≥18 kg/m2 and ≤45 kg/m2. 6. Screening hemoglobin ≥9.0 g/dL, platelets ≥100 K/mL, ANC ≥1500/mL. 7. Able and willing to use adequate contraception until the end of the study.
• \. Capable of providing informed consent and to comply with the protocol.

You may not qualify if:

• Participating in any other study, have received any other investigational drug within 30 days prior to screening or 5-half-lives 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).
• Heart failure due to hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricula dysplasia (ARVD), stress-induced ("Takotsubo") cardiomyopathy, chemotherapy-induced cardiomyopathy, peripartum cardiomyopathy, infiltrative or inflammatory cardiomyopathies, and primary valvular disease.
• Medically documented acute coronary syndrome within 3 months of screening or a medically documented acute MI 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 major surgical procedure within 1 month prior to screening or planned surgical procedure during the study period.
• Sustained systolic blood pressure \<90 mm Hg and/or diastolic blood pressure \<50 mm Hg.
• Sustained resting heart rate \>100 beats per minute sustained for \>15 minutes except in sustained atrial fibrillation when a heart rate of up to 110 beats per minute is acceptable.
• Cerebrovascular accident or hospitalizations for CV (cardiovascular) causes other than routine percutaneous procedures such as device, battery, generator changes or pacemaker lead insertion/ replacement or device generator changes, including HF, chest pain, stroke, transient ischemic attack, or arrhythmias within 3 months prior to randomization.
• At screening have an abnormal or clinically significant 12-lead ECG abnormality that, in the opinion of the Investigator, would affect efficacy or safety evaluation or place the subject at risk.
• History or evidence of clinically significant arrhythmia uncontrolled by drug therapy or use of an implantable defibrillator, long QT syndrome, or evidence of QT prolongation with QTcF \>450 ms for males or QTcF \>470 ms for females prior to randomization.
• Clinically significant renal dysfunction as measured by the estimated GFR \<45 mL/min/1.73m2 at screening, or a clinically significant change in renal function between screening and baseline.
• Clinically significant liver dysfunction as measured by: ALT \>2.0 × ULN, alkaline phosphatase \> 2.0 × ULN, AST \>2.0 × the ULN, or GGT \>2.0 × the ULN or serum bilirubin ≥ 1.2 × the ULN at screening, or a clinically significant change in liver function between screening and baseline.
• Subjects with alteration of the coagulation panel (INR) and/or PT ≥ 1.5 × the ULN; aPTT ≥ 1.5 × ULN, or serum albumin ≤ 3 gm/dL. For subjects on warfarin or other anticoagulants, an INR (or PT) considered by the Principal Investigator as therapeutically appropriate will be allowed.

Sponsors & Collaborators

• Salubris Biotherapeutics Inc: lead

Study Sites (7)

University of Arizona College of Medicine

Tucson, Arizona, 85724-5039, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Harvard Medical School/ Massachusetts General Hospital

Boston, Massachusetts, 02114-2696, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health Science University Hospital

Portland, Oregon, 97239, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Tang WHW, Steiner J, Kassi M, Wheeler MT, Spahillari A, Sweitzer NK, Grodin JL, Solomon N, Singhal S, McEwen AMG, Murphy SL. Single Ascending-Dose Study of Selective ErbB4 Agonist JK07 in Heart Failure With Reduced Ejection Fraction. JACC Basic Transl Sci. 2025 Sep;10(9):101352. doi: 10.1016/j.jacbts.2025.101352. Epub 2025 Jul 29.

  PMID: 40737710 DERIVED

MeSH Terms

Conditions

Heart Failure; Fibromatosis, Gingival, 2

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

This was a Phase 1, single ascending dose study intended to support the continued exploration of JK07 as a HF treatment. As such, these results provide only a very early picture of the potential safety profile and pharmacodynamics of JK07.

Results Point of Contact

• Title: SVP, Clinical Development
• Organization: Salubris Biotherapeutics, Inc

amanda.mcewen@salubrisbio.com

16176459160

Study Officials

• Wilson Tang, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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

Model Details: Double-blind, placebo-controlled, single-ascending dose with single active sentinel subject per cohort

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 24, 2019
• Study Start: September 21, 2020
• Primary Completion: June 8, 2023
• Study Completion: July 7, 2023
• Last Updated: July 9, 2025
• Results First Posted: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)