Trial Search Results

Single-Ascending Dose Study of JK07 in Subjects With HFpEF

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.

Stanford is currently not accepting patients for this trial.

Lead Sponsor:

Salubris Biotherapeutics Inc

Stanford Investigator(s):

Intervention(s):

  • Drug: JK07
  • Drug: Matching Placebo

Phase:

Phase 1

Eligibility


Inclusion Criteria:

   1. 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.

   2. Documented prior objective evidence of heart failure as shown by 1 or more of the
   following criteria:

      1. Previous hospitalization for heart failure with documented radiographic evidence
      of pulmonary congestion.

      2. Elevated left ventricular (LV) end-diastolic pressure or pulmonary capillary
      wedge pressure at rest (≥15 mm Hg) or with exercise (≥25 mm Hg).

      3. Elevated level of NT-proBNP (>400 pg/mL) or brain natriuretic peptide (BNP) (>200
      pg/mL).

      4. Echocardiographic evidence of medial E/e' ratio ≥ 15 or Left Atrial Volume (LAV)
      >58 mL in male patients or >52 mL in female patients.

   3. Adequate acoustic windows on screening resting TTE

   4. Documented structural abnormality consistent with HFpEF confirmed at the screening
   visit by clearly interpretable echocardiography assessment.

   5. Meets 1 or more of the following criteria at the initial screening measurement:

      1. A hs-cTnI >99th percentile

      2. 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).

   6. Body mass index (BMI) ≥18 kg/m2 and ≤45 kg/m2

   7. Screening hemoglobin ≥9.0 g/dL, platelets ≥100x109 /mL, absolute neutrophil count
   (ANC) ≥1500/mL.

   8. 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).

   9. 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).

10. Subject is capable of giving signed informed consent.

11. Subject is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

Cardiac-Related

   1. 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.

   2. Any past participation in a study that has investigated the NRG-1 pathway (e.g.,
   Neucardin, cimaglermin).

   3. 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.

   4. Has a history of syncope within the last 6 months or sustained ventricular tachycardia
   with exercise within the past 6 months.

   5. 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.

   6. Has known moderate or severe aortic valve stenosis, hemodynamically significant mitral
   stenosis, or severe mitral or tricuspid regurgitation at informed consent.

   7. 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.

   8. Diagnosed with medically documented acute coronary syndrome within 3 months of
   screening or a medically documented acute myocardial infarction within 6 months of
   screening.

   9. Cardiac surgery, coronary artery revascularization, percutaneous coronary
   intervention, or valvuloplasty within 3 months prior to screening.

10. Any subject who has received an indication for coronary revascularization within 3
   months prior to screening.

11. 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:

      1. Systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP)
      >100 mmHg

      2. Sustained SBP <90 mmHg and/or DBP <40 mmHg and/or symptomatic hypotension

      3. 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

12. Cerebrovascular accident or hospitalizations for cardiovascular (CV) causes other than
   routine percutaneous procedures (such as device, battery, generator changes or
   pacemaker lead insertion/replacement), including HF, chest pain, stroke, transient
   ischemic attack, or arrhythmias within 3 months prior to screening.

13. Symptomatic carotid stenosis or transient ischemic attack or stroke within 60 days
   prior to informed consent.

14. Has a history of resuscitated sudden cardiac arrest or a known history of appropriate
   implantable cardioverter-defibrillator (ICD) discharge for life-threatening
   ventricular arrhythmia. (Note: history of anti-tachycardia pacing (ATP) is allowed.)

15. Subjects 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.

16. History or evidence of clinically significant arrhythmias 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 during screening
   and/or prior to randomization.

   Non-Cardiac Co-Morbidity

17. Clinically significant renal dysfunction as measured by the estimated glomerular
   filtration rate of <45 mL/min/1.73m2 as calculated by local laboratory standards
   (Cockcroft-Gault equation for estimation of creatinine clearance [CrCl] [Cockcroft and
   Gault 1976]) at screening, or a clinically significant change in renal function
   between screening and baseline.

18. Clinically significant liver dysfunction as measured by: alanine aminotransferase
   (ALT) >2.0 × the upper limit of normal (ULN), alkaline phosphatase > 2.0 × ULN,
   aspartate aminotransferase (AST) >2.0 × ULN, or gamma glutamyl transferase (GGT) >2.0
   × ULN or serum bilirubin ≥ 1.5 × ULN at screening, or a clinically significant change
   in liver function between screening and baseline.

19. Subjects with alteration of the coagulation panel (international normalized ratio
   [INR]) and/or prothrombin time (PT) ≥1.5 × the ULN; activated partial thromboplastin
   time (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.

20. Any subject who by Investigator's judgement, has a significant hematuria or
   proteinuria at screening.

21. Concurrent treatment with Class Ia or III antiarrhythmic drugs if the dosage has been
   adjusted within 2 months prior to informed consent.

22. Positive screening for human immunodeficiency virus antibodies, hepatitis B surface
   antigen, or hepatitis C virus antibodies.

23. 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).

24. 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.

25. 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). All subjects are to undergo cancer
   screening following study enrollment in accordance with American Cancer Society
   Guidelines (See Appendix 1).

26. Pregnant or lactating at screening.

27. Subjects with clinically significant or poorly controlled disease including, but not
   limited to, endocrine (including diabetes and thyroid) disease, pulmonary (requires
   home oxygen, inhalants, steroids >10 mg prednisone equivalent or 2x baseline
   physiologic steroid replacement, primary pulmonary hypertension, history of pulmonary
   emboli), neurological or psychiatric (even mild), GI, hematological, urological,
   immunological, ophthalmic, or orthopedic diseases as determined by the Investigator.

28. Any major surgical procedure within 1 month prior to screening or planned surgical
   procedure during the study period.

29. 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.

30. Subjects with orthopedic impairment which would prohibit credible or adequate
   assessment of 6MWT.

Ages Eligible for Study

18 Years - 85 Years

Genders Eligible for Study

All

Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Jennifer Marino
650-725-6911
Not Recruiting