Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluate the Safety, Tolerability and PK of HF1K16 in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05386823
Recruitment Status : Terminated (The sponsor terminated the study for commercial reasons)
First Posted : May 23, 2022
Last Update Posted : May 23, 2022
Sponsor:
Information provided by (Responsible Party):
HighField Biopharmaceuticals Corporation

Brief Summary:
HF1K16 is an investigational pegylated liposome formulation of tretinoin for injection for the induction of remission in patients with acute promyelocytic leukemia (APL) and for the treatment of solid tumors through targeting myeloid derived suppressor cells (MDSCs). This phase 1 Trial is a Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects to Evaluate the Safety, Tolerability and Pharmacokinetics of HF1K16.

Condition or disease Intervention/treatment Phase
Healthy Drug: HF1K16 Drug: Placebo Phase 1

Detailed Description:

Tretinoin is a naturally occurring vitamin A metabolite that participates in many biological processes. It is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells achieving complete remission (CR). In addition, ATRA and similar retinoids were also discovered to have significant immune-modulating activities towards Myeloid derived suppressor cells (MDSCs) that contribute greatly to cancer growth and progression. Preclinical efficacies of ATRA to induce MDSC differentiation into dendritic cells (DCs) and downregulate their inhibitory effects on cytotoxic T cell activities against cancer have been demonstrated.

HF1K16 is a pegylated liposome formulation of tretinoin developed for improved PK behavior, higher therapeutic index, and more specific targeted mechanism towards MDSCs. The objectives of this study are to assess the safety and tolerability of HF1K16. The ATRA pharmacokinetic parameters will be determined with correlations to the liposome doses administered.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study Following Intravenous Administration of HF1K16 in Healthy Subjects to Evaluate the Safety, Tolerability and Pharmacokinetics of HF1K16
Actual Study Start Date : March 27, 2021
Actual Primary Completion Date : July 30, 2021
Actual Study Completion Date : August 8, 2021

Arm Intervention/treatment
Experimental: HF1K16

Up 32 subjects, comprised of up to 4 cohorts of 8 subjects each, will receive a single IV dose of study drug. Six of the 8 subjects in each cohort will receive HF1K16 and 2 subjects will receive placebo in a blinded manner Cohort 1: up to 3 mg/m2 of HF1K16 or placebo

  • Cohort 2: up to 6 mg/m2 of HF1K16 or placebo
  • Cohort 3: up to 10 mg/m2 of HF1K16 or placebo
  • Cohort 4: up to 13 mg/m2 of HF1K16 or placebo
Drug: HF1K16
A range of doses of HF1K16 will be tested based on the assessment of safety, tolerability and pharmacokinetics.
Other Name: ATRA Injection

Placebo Comparator: Placebo

Up 32 subjects, comprised of up to 4 cohorts of 8 subjects each, will receive a single IV dose of study drug. Six of the 8 subjects in each cohort will receive HF1K16 and 2 subjects will receive placebo in a blinded manner Cohort 1: up to 3 mg/m2 of HF1K16 or placebo

  • Cohort 2: up to 6 mg/m2 of HF1K16 or placebo
  • Cohort 3: up to 10 mg/m2 of HF1K16 or placebo
  • Cohort 4: up to 13 mg/m2 of HF1K16 or placebo
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. To evaluate the safety and tolerability of HF1K16 by AE [ Time Frame: up to 8 days after treatment ]
    Incidence of Adverse Events

  2. To evaluate the safety and tolerability of HF1K16 by ECG from ventricular rate [ Time Frame: up to 8 days after treatment ]
    changes of ventricular rate in bpm per minute

  3. To evaluate the safety and tolerability of HF1K16 by respiration rate of vital signs [ Time Frame: Up to 8 Days ]
    Changes from baseline for respiration rate in breaths per minute

  4. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Red blood cell count [ Time Frame: within 21 days after administration ]
    Changes from baseline for Red blood cell count in 10^12 /L in whole blood

  5. To evaluate the safety and tolerability of HF1K16 by ECG from QRS Duration [ Time Frame: up to 8 days after treatment ]
    Changes from baseline for QRS duration in msec before and after using HF1K16

  6. To evaluate the safety and tolerability of HF1K16 by ECG from QT Interval [ Time Frame: up to 8 days after treatment ]
    Changes from baseline for QT interval in msec before and after using HF1K16.

  7. To evaluate the safety and tolerability of HF1K16 by ECG from QTc Interval [ Time Frame: up to 8 days after treatment ]
    Changes from baseline for QTc interval in msec before and after using HF1K16.

  8. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Red blood cell count in whole blood [ Time Frame: within 21 days after administration ]
    Changes from baseline for Red blood cell count in 10^12 /L in whole blood

  9. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Changes from White blood cell count in whole blood [ Time Frame: within 21 days after administration ]
    Changes from baseline for white blood cell count in 10^9 /L in whole blood

  10. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Neutrophil count in whole blood [ Time Frame: within 21 days after administration ]
    Changes from baseline for neutrophil count in 10^9/L in whole blood

  11. To evaluate the safety and tolerability of HF1K16 by Hemoglobin concentration in whole blood [ Time Frame: within 21 days after administration ]
    Changes from baseline for hemoglobin concentration in g/dL

  12. To evaluate the safety and tolerability of HF1K16 by Prothrombin time [ Time Frame: within 21 days after administration ]
    Changes from baseline for Prothrombin time in s

  13. To evaluate the safety and tolerability of HF1K16 by International standardized ratio [ Time Frame: within 21 days after administration ]
    Changes from baseline for international standardized ratio

  14. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from International sensitivity index [ Time Frame: within 21 days after administration ]
    Changes from baseline for international sensitivity index

  15. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Activated partial thromboplastin time [ Time Frame: within 21 days after administration ]
    Changes from baseline for activated partial thromboplastin time in s

  16. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Total bilirubin concentration [ Time Frame: within 21 days after administration ]
    Changes from baseline for total bilirubin concentration in μmol/L

  17. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from ALT concentration [ Time Frame: within 21 days after administration ]
    Changes from baseline for ALT concentration in U/L

  18. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from AST concentration [ Time Frame: within 21 days after administration ]
    Changes from baseline for AST concentration in U/L

  19. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Total protein concentration [ Time Frame: within 21 days after administration ]
    Changes from baseline for total protein concentration in g/L

  20. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Urea concentration [ Time Frame: within 21 days after administration ]
    Changes from baseline for urea concentration in mmol/L

  21. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Creatinine concentration [ Time Frame: within 21 days after administration ]
    Changes from baseline for creatinine concentration in μmol/L

  22. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Total cholesterol concentration [ Time Frame: within 21 days after administration ]
    Changes from baseline for total cholesterol concentration in mmol/L

  23. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from Triglycerides concentration [ Time Frame: within 21 days after administration ]
    Changes from baseline for triglycerides concentration in mmol/L

  24. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from HDL-C [ Time Frame: within 21 days after administration ]
    Changes from baseline for HDL-C in mmol/L

  25. To evaluate the safety and tolerability of HF1K16 by Laboratory Examination from LDL-C [ Time Frame: within 21 days after administration ]
    Changes from baseline for LDL-C in mmol/L

  26. To evaluate the safety and tolerability of HF1K16 by heart rate of vital signs [ Time Frame: Up to 8 Days ]
    Changes from baseline for heart rate in beats per minute

  27. To evaluate the safety and tolerability of HF1K16 by blood pressure of vital signs [ Time Frame: Up to 8 Days ]
    Changes from baseline for blood pressure in mmHg

  28. To evaluate the safety and tolerability of HF1K16 by body temperature of vital signs [ Time Frame: Up to 8 Days ]
    Changes from baseline for body temperature in Celsius degree


Secondary Outcome Measures :
  1. To characterize the pharmacokinetics with MRT [ Time Frame: Up to 48 hours postdose ]
    Mean Residence Time(MRT) of HF1K16

  2. To characterize the pharmacokinetics with Maximum plasma concentration [ Time Frame: Up to 48 hours postdose ]
    maximum plasma concentration (Cmax) of HF1K16

  3. To characterize the pharmacokinetics of with AUC0-inf [ Time Frame: Up to 48 hours postdose ]
    Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of HF1K16

  4. To characterize the pharmacokinetics with with AUC0-48 [ Time Frame: Up to 48 hours postdose ]
    Area under the plasma concentration-time curve from time 0 to 48hr(AUC00-48hr) of HF1K16

  5. To characterize the pharmacokinetics with Tmax [ Time Frame: Up to 48 hours postdose ]
    Time of maximum concentration (Tmax) of HF1K16

  6. To characterize the pharmacokinetics with T1/2 [ Time Frame: Up to 48 hours postdose ]
    Elimination half-life (T1/2) of HF1K16

  7. To characterize the pharmacokinetics with CL/F [ Time Frame: Up to 48 hours postdose ]
    Descriptive statistics of CL/F (Apparent total body clearance of drug from plasma after dose of HF1K16)

  8. To characterize the pharmacokinetics with VzF [ Time Frame: Up to 48 hours postdose ]
    Descriptive statistics of Vz/F (Apparent volume of distribution during the terminal phase after dose of HF1K16)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Capable of giving informed consent and complying with study procedures;
  2. Between the ages of 18 and 55 years, inclusive;
  3. Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive and body weight not less than 50 kg;
  4. Female subjects must have a negative pregnancy test result at screening and at admission;
  5. Female subjects are:

    1. Surgically sterile for at least 3 months prior to screening by one of the following means:

      • Bilateral tubal ligation
      • Bilateral salpingectomy (with or without oophorectomy)
      • Surgical hysterectomy
      • Bilateral oophorectomy (with or without hysterectomy)
    2. Postmenopausal, defined as the following:

      • Last menstrual period greater than 12 months prior to screening, and
      • Postmenopausal status confirmed by serum follicle stimulating hormone (FSH) and estradiol levels at screening;
  6. Male subjects must agree to utilize a highly effective method of contraception (condom plus spermicide) during heterosexual intercourse from the time of clinic admission until 12 weeks following the end of study visit, and refrain from donating sperm for this same period;
  7. Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, 12-lead ECG, and vital signs;
  8. Have clinical laboratory renal (eGFR, creatinine) and liver (AST, ALT, Total bilirubin) function within normal range and other clinical laboratory results within normal range or outside normal range assessed as clinically non-significant by the Investigator at screening and admission;
  9. Non-smoker and has not been exposed to any products containing nicotine in the last 6 months;
  10. Willing and able to adhere to study restrictions and to be confined at the Clinical Research Unit

Exclusion Criteria:

  1. Clinically significant reported history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator;
  2. Known or suspected malignancy;
  3. Reported history of pancreatitis or gall stones;
  4. Reported history of unexplained syncope, symptomatic hypotension or hypoglycemia;
  5. Reported family history of long QTc syndrome or a QTc of > 450 ms at screening;
  6. Reported history of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance;
  7. Poor venous access;
  8. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (anti-HCV) at screening;
  9. Donated or lost >500 mL of blood in the previous 3 months prior to screening;
  10. Taken an investigational drug or participated in a clinical trial within 30 days (or 5 half-lives) prior to first dose of study drug, whichever is longer;
  11. Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug;
  12. Taken any prescription or non-prescription drugs and herbal medication known to be CYP450 inducers, inhibitors, and substrates within 14 days prior to screening (See Appendix B);
  13. Taken daily Vitamin A supplement within 3 months prior to screening;
  14. Major surgery or hospitalization within 6 months prior to screening that in the Investigators opinion would put the subject or study conduct at risk;
  15. A history of prescription drug abuse, or illicit drug use within 9 months prior to screening;
  16. A history of alcohol abuse according to medical history (≥ 2 drinks per day for male and ≥ 1 drink per day for female) within 9 months prior to screening;
  17. A positive screen for alcohol, drugs of abuse at screening or admission;
  18. An unwillingness or inability to comply with food and beverage restrictions during study participation;
  19. Use of over-the-counter (OTC) medication within 7 days, and/or herbal medications (including herbal teas, garlic extracts) within 7 days prior to first dose of study drug;
  20. Have a history of allergic reactions (either spontaneous or following drug administration) to ATRA or to any of the excipients or related compounds, including vitamin A;
  21. Any condition or finding that in the Investigators opinion would put the subject or study conduct at risk if the subject were to participate in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05386823


Locations
Layout table for location information
United States, New Jersey
Frontage Clinical Services, Inc.
Secaucus, New Jersey, United States, 07094
Sponsors and Collaborators
HighField Biopharmaceuticals Corporation
Investigators
Layout table for investigator information
Principal Investigator: Gregory Tracey Secaucus, New Jersey, United States
Layout table for additonal information
Responsible Party: HighField Biopharmaceuticals Corporation
ClinicalTrials.gov Identifier: NCT05386823    
Other Study ID Numbers: HF1K16-101
First Posted: May 23, 2022    Key Record Dates
Last Update Posted: May 23, 2022
Last Verified: May 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No