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

Primary Purpose

Phenylketonuria

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
JNT-517 Suspension
Placebo Suspension
JNT-517 Tablet
Placebo Tablet
Sponsored by
Jnana Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Phenylketonuria focused on measuring PKU

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Key Inclusion Criteria: Parts A, B, and C: Males and females 18 to 55 years of age. Medically healthy with no clinically significant medical history. Body mass index (BMI) of 18-40 kg/m2 and total body weight >50 kg (110 lbs). Non-smoker for at least 2 weeks prior to dosing and willing to abstain during the study. Part D: Males and females 18 to 65 years of age, inclusive. Diagnosis of PKU with a confirmed genotype. At least 2 plasma Phe levels >600 μM over the past 12 months. BMI of 18-40 kg/m2. All Parts: Females of childbearing potential must agree to use 2 highly effective contraceptive methods. Capable of giving signed informed consent and able to comply with study procedures. Key Exclusion Criteria: All Parts: 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. Positive for hepatitis B or C or human immunodeficiency virus. Any history of malignancy in the last 5 years, excluding non-melanoma skin cancer. Any history of liver disease. Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion. Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer). History of drug/alcohol abuse in the last year. Current, recent, or suspected infection within 4 weeks of Screening of SARS-CoV-2/COVID-19. Received a vaccine for SARS-CoV-2/COVID-19 within 14 days of Screening. Unable to tolerate oral medication. Allergy to JNT-517 or any component of the investigational product. Received >50 mL of blood or plasma within 30 days of Screening or >500 mL of blood or plasma within 60 days of Screening.

Sites / Locations

  • University of Florida College of MedicineRecruiting
  • University of South FloridaRecruiting
  • Rare Disease ResearchRecruiting
  • Ann & Robert H. Lurie Children's Hospital of ChicagoRecruiting
  • Oregon Health & Sciences UniversityRecruiting
  • Children's Hospital of PhiladelphiaRecruiting
  • UPMC Children's Hospital of PittsburghRecruiting
  • UT Southwestern Medical CenterRecruiting
  • Nucleus Network MelbourneRecruiting
  • Westmead HospitalRecruiting
  • Mater Misericordia LtdRecruiting
  • Royal Adelaide HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

JNT-517 SAD (Part A)

JNT-517 MAD (Part B)

JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C)

JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C)

JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C)

JNT-517 PKU (Part D)

Arm Description

Single dose of JNT-517 or placebo in fasted state.

JNT-517 or placebo once or twice daily for 14 days, with first daily dose given after an overnight fast.

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.

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.

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.

JNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C.

Outcomes

Primary Outcome Measures

Number of participants with treatment-emergent adverse events
Reported based on results of 12-lead ECGs, vital signs, clinical laboratory tests, and other medical assessments.

Secondary Outcome Measures

Plasma area under the concentration-time curve (AUC) of JNT-517
Maximum observed plasma concentration (Cmax) of JNT-517
Time to maximum plasma concentration (Tmax) of JNT-517
Plasma terminal half-life (t1/2) of JNT-517
Comparison of Tmax of JNT-517 in fed and fasted states
Part C only
Comparison of Cmax of JNT-517 in fed and fasted states
Part C only
Comparison of AUC of JNT-517 in fed and fasted states
Part C only
Changes in urinary amino acid levels
Part D only. Urine samples will be collected at the indicated timepoints and analyzed for amino acid levels, including Phe.

Full Information

First Posted
February 11, 2023
Last Updated
September 20, 2023
Sponsor
Jnana Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05781399
Brief Title
First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 31, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jnana Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonuria
Keywords
PKU

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Parts A, B, and D are blinded. Part C is open-label.
Allocation
Randomized
Enrollment
112 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
JNT-517 SAD (Part A)
Arm Type
Experimental
Arm Description
Single dose of JNT-517 or placebo in fasted state.
Arm Title
JNT-517 MAD (Part B)
Arm Type
Experimental
Arm Description
JNT-517 or placebo once or twice daily for 14 days, with first daily dose given after an overnight fast.
Arm Title
JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C)
Arm Type
Experimental
Arm Description
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.
Arm Title
JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C)
Arm Type
Experimental
Arm Description
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.
Arm Title
JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C)
Arm Type
Experimental
Arm Description
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.
Arm Title
JNT-517 PKU (Part D)
Arm Type
Experimental
Arm Description
JNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C.
Intervention Type
Drug
Intervention Name(s)
JNT-517 Suspension
Intervention Description
JNT-517 in on-site compounded suspension
Intervention Type
Drug
Intervention Name(s)
Placebo Suspension
Intervention Description
On-site compounded placebo suspension
Intervention Type
Drug
Intervention Name(s)
JNT-517 Tablet
Intervention Description
JNT-517 tablets, 25 mg and 75 mg
Intervention Type
Drug
Intervention Name(s)
Placebo Tablet
Intervention Description
Matching film-coated placebo tablet
Primary Outcome Measure Information:
Title
Number of participants with treatment-emergent adverse events
Description
Reported based on results of 12-lead ECGs, vital signs, clinical laboratory tests, and other medical assessments.
Time Frame
Parts A and C: Screening to Day 8; Part B: Screening to Day 21; Part D: Screening to Day 35
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
Comparison of Tmax of JNT-517 in fed and fasted states
Description
Part C only
Time Frame
Pre-dose to 72 hrs post-dose on Day 1
Title
Comparison of Cmax of JNT-517 in fed and fasted states
Description
Part C only
Time Frame
Pre-dose to 72 hrs post-dose on Day 1
Title
Comparison of AUC of JNT-517 in fed and fasted states
Description
Part C only
Time Frame
Pre-dose to 72 hrs post-dose on Day 1
Title
Changes in urinary amino acid levels
Description
Part D only. Urine samples will be collected at the indicated timepoints and analyzed for amino acid levels, including Phe.
Time Frame
Screening and Days 1, 7, 14, 21, 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria: Parts A, B, and C: Males and females 18 to 55 years of age. Medically healthy with no clinically significant medical history. Body mass index (BMI) of 18-40 kg/m2 and total body weight >50 kg (110 lbs). Non-smoker for at least 2 weeks prior to dosing and willing to abstain during the study. Part D: Males and females 18 to 65 years of age, inclusive. Diagnosis of PKU with a confirmed genotype. At least 2 plasma Phe levels >600 μM over the past 12 months. BMI of 18-40 kg/m2. All Parts: Females of childbearing potential must agree to use 2 highly effective contraceptive methods. Capable of giving signed informed consent and able to comply with study procedures. Key Exclusion Criteria: All Parts: 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. Positive for hepatitis B or C or human immunodeficiency virus. Any history of malignancy in the last 5 years, excluding non-melanoma skin cancer. Any history of liver disease. Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion. Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer). History of drug/alcohol abuse in the last year. Current, recent, or suspected infection within 4 weeks of Screening of SARS-CoV-2/COVID-19. Received a vaccine for SARS-CoV-2/COVID-19 within 14 days of Screening. Unable to tolerate oral medication. Allergy to JNT-517 or any component of the investigational product. Received >50 mL of blood or plasma within 30 days of Screening or >500 mL of blood or plasma within 60 days of Screening.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toby Vaughn
Phone
1-513-505-0770
Email
tvaughn@jnanatx.com
First Name & Middle Initial & Last Name or Official Title & Degree
John Throup, PhD
Email
clinicaltrials@jnanatx.com
Facility Information:
Facility Name
University of Florida College of Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roberto Zori, MD
Phone
352-273-7763
Email
zorirt@peds.ufl.edu
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33620
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amarillas Sanchez-Valle, MD
Phone
813-417-5095
Email
gmresearch@usf.edu
Facility Name
Rare Disease Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valery Sevillanos
Phone
470-666-1884
Email
valery.sevillanos@rarediseaseresearch.com
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Phillip Luu
Phone
312-227-6128
Email
pluu@luriechildrens.org
Facility Name
Oregon Health & Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elaine Sim, MS,RD,LD
Phone
503-494-0232
Email
sim@ohsu.edu
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Phillip
Phone
973-847-3056
Email
phillipL@chop.edu
Facility Name
UPMC Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nyesha S Rainey, CRC
Phone
412-692-8049
Email
brooksns@upmc.edu
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juana Luevano
Phone
214-645-7411
Email
juana.luevano@utsouthwestern.edu
Facility Name
Nucleus Network Melbourne
City
Melbourne
State/Province
Melbourne VIC
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ofer Gonen, MD
Phone
+61 3 8593 9800
Email
o.gonen@nucleusnetwork.com
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pamela Cheung
Phone
+61 2 8890 3626
Email
pamela.cheung@health.nsw.gov.au
Facility Name
Mater Misericordia Ltd
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yvonne M Gautam
Phone
+61 7 3163 3484
Email
yvonne.gautam@mater.uq.edu.au
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathy Heyman
Phone
+61 8 7074 4404
Email
kathy.heyman@sa.gov.au

12. IPD Sharing Statement

Learn more about this trial

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

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