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First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria

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ClinicalTrials.gov Identifier: NCT05781399
Recruitment Status : Recruiting
First Posted : March 23, 2023
Last Update Posted : January 12, 2024
Sponsor:
Information provided by (Responsible Party):
Jnana Therapeutics

Tracking Information
First Submitted Date  ICMJE February 11, 2023
First Posted Date  ICMJE March 23, 2023
Last Update Posted Date January 12, 2024
Actual Study Start Date  ICMJE October 31, 2022
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2023)		 Number of participants with treatment-emergent adverse events [ Time Frame: Parts A and C: Screening to Day 8; Part B: Screening to Day 21; Part D: Screening to Day 35 ]
Reported based on results of 12-lead ECGs, vital signs, clinical laboratory tests, and other medical assessments.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2023)
  • Plasma area under the concentration-time curve (AUC) of JNT-517 [ Time Frame: Parts A and C: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D: pre-dose to 4 hrs post-dose on Days 1, 14, 28 ]
  • Maximum observed plasma concentration (Cmax) of JNT-517 [ Time Frame: Parts A and C: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D: pre-dose to 4 hrs post-dose on Days 1, 14, 28 ]
  • Time to maximum plasma concentration (Tmax) of JNT-517 [ Time Frame: Parts A and C: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D: pre-dose to 4 hrs post-dose on Days 1, 14, 28 ]
  • Plasma terminal half-life (t1/2) of JNT-517 [ Time Frame: Parts A and C: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D: pre-dose to 4 hrs post-dose on Days 1, 14, 28 ]
  • Comparison of Tmax of JNT-517 in fed and fasted states [ Time Frame: Pre-dose to 72 hrs post-dose on Day 1 ]
    Part C only
  • Comparison of Cmax of JNT-517 in fed and fasted states [ Time Frame: Pre-dose to 72 hrs post-dose on Day 1 ]
    Part C only
  • Comparison of AUC of JNT-517 in fed and fasted states [ Time Frame: Pre-dose to 72 hrs post-dose on Day 1 ]
    Part C only
  • Changes in urinary amino acid levels [ Time Frame: Screening and Days 1, 7, 14, 21, 28 ]
    Part D only. Urine samples will be collected at the indicated timepoints and analyzed for amino acid levels, including Phe.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria
Official Title  ICMJE A Phase 1, First-In-Human, Multiple Part, Single Ascending and Multiple Dose Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria
Brief Summary

The goal of Parts A and B of this Phase 1, first-in-human, randomized study is to assess the safety, tolerability, and pharmacokinetics (PK) of single (SAD) and multiple (MAD) ascending doses of oral JNT-517 in healthy participants. In Part C, the goal is to evaluate the differences in bioavailability between a tablet and suspension formulation of JNT-517 and the food effect in healthy volunteers. All participants in Part C will receive JNT-517. The goal of Part D is to assess the safety, tolerability, PK, and effect on urinary Phe and other amino acids of JNT-517 in participants with phenylketonuria (PKU). Participants in Part D will receive either JNT-517 or placebo and will be blinded to their treatment assignment.

The study consists of 4 parts:

  • Part A: SAD in healthy participants -randomized, double-blind, placebo-controlled
  • Part B: MAD in healthy participants (14 days)-randomized, double-blind, placebo-controlled
  • Part C: Relative bioavailability of 2 formulations and food effect in healthy participants-randomized, open-label
  • Part D: Phase 1b in participants with PKU (4 weeks)-randomized, double-blind, placebo-controlled

In each part, participants will complete a Screening Period, a Treatment Period, and a Follow-up Period for safety.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
The study will be conducted in 4 parts: Parts A, B, C, and D. This study will be seamless, meaning various study parts could begin while other parts are still ongoing, but dose escalation will occur only after satisfactory review of safety and tolerability data from a minimum of 6 participants completing through Day 3, and available PK data.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Parts A, B, and D are blinded. Part C is open-label.
Primary Purpose: Treatment
Condition  ICMJE Phenylketonuria
Intervention  ICMJE
  • Drug: JNT-517 Suspension
    JNT-517 in on-site compounded suspension
  • Drug: Placebo Suspension
    On-site compounded placebo suspension
  • Drug: JNT-517 Tablet
    JNT-517 tablets, 25 mg and 75 mg
  • Drug: Placebo Tablet
    Matching film-coated placebo tablet
Study Arms  ICMJE
  • Experimental: JNT-517 SAD (Part A)
    Single dose of JNT-517 or placebo in fasted state.
    Interventions:
    • Drug: JNT-517 Suspension
    • Drug: Placebo Suspension
  • Experimental: JNT-517 MAD (Part B)
    JNT-517 or placebo once or twice daily for 14 days, with first daily dose given after an overnight fast.
    Interventions:
    • Drug: JNT-517 Suspension
    • Drug: Placebo Suspension
  • Experimental: JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C)
    Single dose of JNT-517 suspension, JNT-517 tablet in a fasted state, and JNT-517 tablet in a fed state in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.
    Interventions:
    • Drug: JNT-517 Suspension
    • Drug: JNT-517 Tablet
  • Experimental: JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C)
    Single dose of JNT-517 tablet in a fasted state, JNT-517 tablet in a fed state, and JNT-517 suspension in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.
    Interventions:
    • Drug: JNT-517 Suspension
    • Drug: JNT-517 Tablet
  • Experimental: JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C)
    Single dose of JNT-517 tablet in a fed state, JNT-517 suspension, and JNT-517 tablet in a fasted state in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.
    Interventions:
    • Drug: JNT-517 Suspension
    • Drug: JNT-517 Tablet
  • Experimental: JNT-517 PKU (Part D)
    JNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C.
    Interventions:
    • Drug: JNT-517 Tablet
    • Drug: Placebo Tablet
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: March 10, 2023)		 112
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2025
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

Parts A, B, and C:

  1. Males and females 18 to 55 years of age.
  2. Medically healthy with no clinically significant medical history.
  3. Body mass index (BMI) of 18-40 kg/m2 and total body weight >50 kg (110 lbs).

  4. Non-smoker for at least 2 weeks prior to dosing and willing to abstain during the study.

    Part D:

  5. Males and females 18 to 65 years of age, inclusive.
  6. Diagnosis of PKU with a confirmed genotype.
  7. At least 2 plasma Phe levels >600 μM over the past 12 months.

  8. BMI of 18-40 kg/m2.

    All Parts:

  9. Females of childbearing potential must agree to use 2 highly effective contraceptive methods.
  10. Capable of giving signed informed consent and able to comply with study procedures.

Key Exclusion Criteria:

All Parts:

  1. Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
  2. Positive for hepatitis B or C or human immunodeficiency virus.
  3. Any history of malignancy in the last 5 years, excluding non-melanoma skin cancer.
  4. Any history of liver disease.
  5. Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
  6. Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer).
  7. History of drug/alcohol abuse in the last year.
  8. Current, recent, or suspected infection within 4 weeks of Screening of SARS-CoV-2/COVID-19.
  9. Received a vaccine for SARS-CoV-2/COVID-19 within 14 days of Screening.
  10. Unable to tolerate oral medication.
  11. Allergy to JNT-517 or any component of the investigational product.
  12. Received >50 mL of blood or plasma within 30 days of Screening or >500 mL of blood or plasma within 60 days of Screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Toby Vaughn 1-513-505-0770 tvaughn@jnanatx.com
Contact: John Throup, PhD clinicaltrials@jnanatx.com
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05781399
Other Study ID Numbers  ICMJE JNT517-101
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 Not Provided
Current Responsible Party Jnana Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Jnana Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Jnana Therapeutics
Verification Date January 2024

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