Heart Failure With Reduced Ejection FractionPhase 1NCT04210375
Study of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF)
A Phase 1 study testing JK07 in people with Heart Failure With Reduced Ejection Fraction, run by Salubris Biotherapeutics Inc at 7 sites in United States.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction
- What is being tested?
- JK07
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 7 sitesUnited States
- Study dates
- 21 Sep 2020to 7 Jul 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 5. 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.
- 8. Capable of providing informed consent and to comply with the protocol.
Who cannot join
- 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.
Show all 25Show fewer
- 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.
- Subjects with values of CPK and/or CK-MB >2.5 times normal institutional limits at screening.
- Any subject who by Investigator's judgement, has a significant hematuria or proteinuria at screening.
- Concurrent treatment with Class Ia or III antiarrhythmic drugs (the medication must have been discontinued more than 2 months before informed consent).
- Positive screening for HIV antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies.
- Known history of or active alcohol abuse (no more than 14 units/week for males or 7 units/week for females) or use of illicit drugs within 1 year prior to randomization (excluding recreational use of marijuana or cannabidiol [CBD]-based products.
- Other medical or psychiatric condition that, in the opinion of the Investigator, would preclude obtaining voluntary consent/assent or would confound the secondary objectives of study.
- A history of pathologically-confirmed malignancy of any type or any pathologically-confirmed pre-malignant condition (e.g. ductal carcinoma in situ, colonic polyp with premalignant diagnosis, or cervical atypia).
- Pregnant or lactating female subjects at screening.
- Subjects with clinically significant or poorly controlled disease including, but not limited to, endocrine (including diabetes and thyroid) disease, neurological or psychiatric (even mild), GI, hematological, urological, immunological, or ophthalmic diseases as determined by the Investigator.
- Subjects who are not non-smokers or light smokers (no more than 5 cigarettes per day) and who cannot abstain from smoking from 2 weeks prior to the administration of IP through the end of the study.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Harvard Medical School/ Massachusetts General Hospital
Boston, Massachusetts, 02114-2696
Cleveland Clinic
Cleveland, Ohio, 44195
University of Texas Southwestern
Dallas, Texas, 75390
Houston Methodist Hospital
Houston, Texas, 77030
Oregon Health Science University Hospital
Portland, Oregon, 97239
Stanford University Medical Center
Stanford, California, 94305
University of Arizona College of Medicine
Tucson, Arizona, 85724-5039
About this study
Official title: A Randomized, Double-Blind, Placebo-controlled, Single-ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF)
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.
Read the detailed description
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 HF subjects 18 to 80 years of age with LVEF ≤40%. Subjects must have been maintained on an optimal HF medical regimen for at least 2 months prior to enrollment and remain on the same treatment regimen throughout the course of the study, per the 2017 ACC/AHA/HFSA) treatment guidelines.
At screening, eligible subjects will undergo a physical examination, 2-dimensional transthoracic echocardiography (2D-TTE), ECG assessment, blood sampling for laboratory parameters, and urine testing. Safety assessments at screening will include hematology, biochemistry, coagulation, liver, and thyroid function.
Subjects will be observed in the hospital on continuous telemetry from the time of hospital admission until shortly before discharge approximately 48 hours later. During this time, they will additionally have safety labs, vital signs, PK and biomarker samples collected, and ECGs and 2D-TTEs performed.
Only a single dose of the investigational product will be administered and only a single hospital admission is planned per subject during the study. Subjects will complete follow-up visits through 180 days after administration of the investigational product.
- Being tested
- JK07, Matching Placebo
- Keywords
- heart failure, HFrEF, neuregulin 1, NRG-1, heregulin, HER3, HER4, ErbB3, ErbB4, reduced ejection fraction
- Medical subject headings
- Heart Failure, Fibromatosis, Gingival, 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JK07Drug
Recombinant fusion protein consisting of a fully humanized immunoglobulin G1 monoclonal antibody and an active polypeptide fragment of the human growth factor NRG-1
Matching PlaceboDrug
Vehicle control
| Study group | Role | What they receive |
|---|---|---|
| JK07 | Active comparator | Single dose of JK07 administered by intravenous infusion over 60 minutes Receives: Drug: JK07 |
| Matching Placebo | Placebo comparator | Single dose of placebo administered by intravenous infusion over 60 minutes Receives: Drug: Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and Severity of Treatment-emergent Adverse Events [Safety and Tolerability]
All safety information is collected and evaluated.
Measured: Screening to 30 days
Secondary outcomes (3)
AUC(0-last) of JK07
Area under the concentration (time curve to the last quantifiable concentration) from blood samples taken on Days 1-4, and Days 7, 11, 15, 22, 30, and 60.
Measured: Baseline to 60 days
Cmax of JK07
Maximum concentration from blood samples taken on Days 1-4, and Days 7, 11, 15, 22, 30, and 60.
Measured: Baseline to 60 days
t1/2 of JK07
Half-life from blood samples taken on Days 1-4, and Days 7, 11, 15, 22, 30, and 60.
Measured: Baseline to 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2019
- Study start21 Sep 2020
- Primary completion8 Jun 2023
- Study completion7 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, placebo-controlled, single-ascending dose with single active sentinel subject per cohort
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Salubris Biotherapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wilson Tang, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04210375
- Sponsor's protocol ID
- JK07.1.01
- Status last verified
- Jul 2025
- First submitted
- 17 Dec 2019
- Last updated
- 9 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40737710
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-controlled, Single-ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF)
- ClinicalTrials.gov ID
- NCT04210375
- Acronym / sponsor ID
- JK07.1.01
- Keywords
- heart failure, HFrEF, neuregulin 1, NRG-1, heregulin, HER3, HER4, ErbB3
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Salubris Biotherapeutics IncIndustry (pharma, biotech, devices)
- Study start
- 21 Sep 2020 (actual)
- Primary completion
- 8 Jun 2023 (actual)
- Study completion
- 7 Jul 2023 (actual)
- First posted
- 24 Dec 2019 (actual)
- Results
- Posted 9 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 HF subjects 18 to 80 years of age with LVEF ≤40%. Subjects must have been maintained on an optimal HF medical regimen for at least 2 months prior to enrollment and remain on the same treatment regimen throughout the course of the study, per the 2017 ACC/AHA/HFSA) treatment guidelines.
At screening, eligible subjects will undergo a physical examination, 2-dimensional transthoracic echocardiography (2D-TTE), ECG assessment, blood sampling for laboratory parameters, and urine testing. Safety assessments at screening will include hematology, biochemistry, coagulation, liver, and thyroid function.
Subjects will be observed in the hospital on continuous telemetry from the time of hospital admission until shortly before discharge approximately 48 hours later. During this time, they will additionally have safety labs, vital signs, PK and biomarker samples collected, and ECGs and 2D-TTEs performed.
Only a single dose of the investigational product will be administered and only a single hospital admission is planned per subject during the study. Subjects will complete follow-up visits through 180 days after administration of the investigational product.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, placebo-controlled, single-ascending dose with single active sentinel subject per cohort
| Arm | Type | Receives |
|---|---|---|
| JK07 | Active comparator | Drug: JK07Single dose of JK07 administered by intravenous infusion over 60 minutes |
| Matching Placebo | Placebo comparator | Drug: Matching PlaceboSingle dose of placebo administered by intravenous infusion over 60 minutes |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JK07Recombinant fusion protein consisting of a fully humanized immunoglobulin G1 monoclonal antibody and an active polypeptide fragment of the human growth factor NRG-1 | Drug | JK07 |
| Matching PlaceboVehicle control | Drug | Matching Placebo |
Primary outcome
Incidence and Severity of Treatment-emergent Adverse Events [Safety and Tolerability]
Time frame: Screening to 30 days
All safety information is collected and evaluated.
3 secondary outcomes
AUC(0-last) of JK07
Time frame: Baseline to 60 days
Cmax of JK07
Time frame: Baseline to 60 days
t1/2 of JK07
Time frame: Baseline to 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40737710Tang 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wilson Tang, MD principal investigator
The Cleveland Clinic
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JK07 in people with Heart Failure With Reduced Ejection Fraction, run by Salubris Biotherapeutics Inc at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and Severity of Treatment-emergent Adverse Events [Safety and Tolerability] (time frame: Screening to 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04210375, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2025.