The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
Phenylketonuria Drug: JNT-517 Suspension Drug: Placebo Suspension Drug: JNT-517 Tablet Drug: Placebo Tablet Phase 1

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
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
Official Title: 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
Actual Study Start Date : October 31, 2022
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Phenylketonuria

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: JNT-517 SAD (Part A)
Single dose of JNT-517 or placebo in fasted state.
 Drug: JNT-517 Suspension
JNT-517 in on-site compounded suspension

Drug: Placebo Suspension
On-site compounded 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.
 Drug: JNT-517 Suspension
JNT-517 in on-site compounded suspension

Drug: Placebo Suspension
On-site compounded 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.
 Drug: JNT-517 Suspension
JNT-517 in on-site compounded suspension

Drug: JNT-517 Tablet
JNT-517 tablets, 25 mg and 75 mg
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.
 Drug: JNT-517 Suspension
JNT-517 in on-site compounded suspension

Drug: JNT-517 Tablet
JNT-517 tablets, 25 mg and 75 mg
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.
 Drug: JNT-517 Suspension
JNT-517 in on-site compounded suspension

Drug: JNT-517 Tablet
JNT-517 tablets, 25 mg and 75 mg
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.
 Drug: JNT-517 Tablet
JNT-517 tablets, 25 mg and 75 mg

Drug: Placebo Tablet
Matching film-coated placebo tablet


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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

  6. 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

  7. 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

  8. 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT05781399


Contacts
Layout table for location contacts
Contact: Toby Vaughn 1-513-505-0770 tvaughn@jnanatx.com
Contact: John Throup, PhD clinicaltrials@jnanatx.com

Locations
Layout table for location information
United States, Florida
University of Florida College of Medicine Recruiting
Gainesville, Florida, United States, 32610
Contact: Roberto Zori, MD    352-273-7763    zorirt@peds.ufl.edu   
University of South Florida Recruiting
Tampa, Florida, United States, 33620
Contact: Amarillas Sanchez-Valle, MD    813-417-5095    gmresearch@usf.edu   
United States, Georgia
Rare Disease Research Recruiting
Atlanta, Georgia, United States, 30329
Contact: Valery Sevillanos    470-666-1884    valery.sevillanos@rarediseaseresearch.com   
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Phillip Luu    312-227-6128    pluu@luriechildrens.org   
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: William B Rizzo, MD    402-559-2560    wrizzo@unmc.edu   
United States, Oregon
Oregon Health & Sciences University Recruiting
Portland, Oregon, United States, 97239
Contact: Elaine Sim, MS,RD,LD    503-494-0232    sim@ohsu.edu   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jennifer Phillip    973-847-3056    phillipL@chop.edu   
UPMC Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Nyesha S Rainey, CRC    412-692-8049    brooksns@upmc.edu   
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Juana Luevano    214-645-7411    juana.luevano@utsouthwestern.edu   
University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Emily Garcia    713-500-0220    Emaily.garcia@uth.tmc.edu   
United States, Utah
Utah Health - The University of Utah Hospital Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Carrie Bailey, BS CCRC    801-587-3605    ped_mgr@lists.hsc.utah.edu   
Australia, Melbourne VIC
Nucleus Network Melbourne Recruiting
Melbourne, Melbourne VIC, Australia, 3004
Contact: Ofer Gonen, MD    +61 3 8593 9800    o.gonen@nucleusnetwork.com   
Australia, New South Wales
Westmead Hospital Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Pamela Cheung    +61 2 8890 3626    pamela.cheung@health.nsw.gov.au   
Australia, Queensland
Mater Misericordia Ltd Recruiting
South Brisbane, Queensland, Australia, 4101
Contact: Yvonne M Gautam    +61 7 3163 3484    yvonne.gautam@mater.uq.edu.au   
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Kathy Heyman    +61 8 7074 4404    kathy.heyman@sa.gov.au   
Sponsors and Collaborators
Jnana Therapeutics
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Jnana Therapeutics
ClinicalTrials.gov Identifier: NCT05781399    
Other Study ID Numbers: JNT517-101
First Posted: March 23, 2023    Key Record Dates
Last Update Posted: January 12, 2024
Last Verified: January 2024

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jnana Therapeutics:
PKU
Additional relevant MeSH terms:
Layout table for MeSH terms
Phenylketonurias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
 Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases