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

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ClinicalTrials.gov Identifier: NCT04210375
Recruitment Status : Recruiting
First Posted : December 24, 2019
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
Salubris Biotherapeutics Inc

Tracking Information
First Submitted Date  ICMJE December 17, 2019
First Posted Date  ICMJE December 24, 2019
Last Update Posted Date February 16, 2021
Actual Study Start Date  ICMJE September 21, 2020
Estimated Primary Completion Date September 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 23, 2019)
Incidence and severity of treatment-emergent adverse events [safety and tolerability] [ Time Frame: Screening to 30 days ]
All safety information will be collected and evaluated
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2019)
Pharmacokinetics (area under the concentration versus time curve) of JK07 [ Time Frame: Baseline to 60 days ]
Blood samples will be taken on Days 1-4, and Days 7, 11, 15, 22, 30, and 60
Original Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2019)
Pharmacokinetics of JK07 [ Time Frame: Baseline to 60 days ]
Area under the concentration versus time curve
Current Other Pre-specified Outcome Measures
 (submitted: December 23, 2019)
  • Left ventricular and systemic vascular resistance assessment [ Time Frame: Screening to 180 days ]
    2D-transthoracic echocardiography
  • Biomarkers [ Time Frame: Screening to 180 days ]
    Assessment of potential predictive biomarkers
  • Concentration-QT correlation [ Time Frame: Baseline to Day 3 ]
    Assess the possible relationship between JK07 plasma concentrations and any observed change in QT intervals
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF)
Official Title  ICMJE 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)
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.

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 3 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double-blind, placebo-controlled, single-ascending dose with single active sentinel subject per cohort
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Heart Failure With Reduced Ejection Fraction
Intervention  ICMJE
  • Drug: JK07
    Recombinant fusion protein consisting of a fully human immunoglobulin G1 monoclonal antibody and an active polypeptide fragment of the human growth factor NRG-1
  • Drug: Matching Placebo
    Vehicle control
Study Arms  ICMJE
  • Active Comparator: JK07
    Single dose of JK07 administered by intravenous infusion over 60 minutes
    Intervention: Drug: JK07
  • Placebo Comparator: Matching Placebo
    Single dose of placebo administered by intravenous infusion over 60 minutes
    Intervention: Drug: Matching Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 23, 2019)
63
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 15, 2022
Estimated Primary Completion Date September 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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.
  2. Stable HF defined as no hospitalizations for cardiac-related issues within the previous 3 months prior to the screening visit or between screening and randomization, other than for routine device generator changes.
  3. Subjects with clearly interpretable echocardiographic images and with a screening LVEF ≤ 40% in the absence of ≥ Grade 3 valvular disease on 2D-TTE.
  4. Subjects must be taking clinician-directed appropriate pharmacological therapy for HF as per the 2017 ACC/AHA/HFSA treatment guidelines at stable doses (except for diuretics) for at least 3 months prior to screening. Subjects with implantable cardioverter-defibrillators (ICDs), if the devices are not "pacing", are eligible.
  5. Body mass index ≥18 kg/m2 and ≤40 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.

Exclusion Criteria:

  1. 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.
  2. Any past participation in a study that has investigated the NRG-1 pathway (e.g., Neucardin, Cimaglermin).
  3. 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.
  4. Acute coronary syndrome within 3 months of screening or acute MI within 6 months of screening.
  5. Cardiac surgery, coronary artery revascularization, percutaneous coronary intervention, or valvuloplasty within 3 months prior to screening.
  6. Any subject who has received an indication for coronary revascularization within 3 months prior to screening.
  7. Any major surgical procedure within 1 month prior to screening or planned surgical procedure during the study period.
  8. Sustained systolic blood pressure <100 mm Hg and/or diastolic blood pressure <50 mm Hg.
  9. Sustained resting heart rate >100 beats per minute.
  10. Cerebrovascular accident or hospitalizations for CV (cardiovascular) causes other than routine device generator changes, including HF, chest pain, stroke, transient ischemic attack, or arrhythmias within 3 months prior to randomization.
  11. At screening have an abnormal or clinically significant 12-lead ECG abnormality, ei.; (QRS >120 msec, PR >210 msec, heart rate (HR) <45 bpm, sustained HR >100 bpm) that, in the opinion of the Investigator, would affect efficacy or safety evaluation or place the subject at risk.
  12. 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.
  13. 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.
  14. 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.
  15. 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/PTT) considered by the Principal Investigator as therapeutically appropriate will be allowed.
  16. Subjects with values of CPK and/or CK-MB >2.5 times normal institutional limits at screening.
  17. Any subject who by Investigator's judgement, has a significant hematuria or proteinuria at screening.
  18. Concurrent treatment with Class I or III antiarrhythmic drugs (unless the medication was discontinued more than 3 months before proposed enrollment).
  19. Positive screening for HIV antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies.
  20. 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 other than recreational use of marijuana or cannabis-based products.
  21. 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.
  22. A history of malignancy of any type or any pre-malignant condition (e.g. ductal carcinoma in situ, colonic polyp, or cervical atypia). All subjects are to undergo cancer screening following study enrollment in accordance with American Cancer Society Guidelines.
  23. Pregnant or lactating female subjects at screening.
  24. 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.
  25. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sam Murphy, PhD 617-584-3853 sam.murphy@salubrisbio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04210375
Other Study ID Numbers  ICMJE JK07.1.01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Salubris Biotherapeutics Inc
Study Sponsor  ICMJE Salubris Biotherapeutics Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Wilson Tang, MD The Cleveland Clinic
PRS Account Salubris Biotherapeutics Inc
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP