What side effects are associated with this type of intervention?

Common treatments for Phenylketonuria (PKU) that modulate phenylalanine metabolism, such as sapropterin dihydrochloride (BH4) and pegvaliase, often have side effects including headache, gastrointestinal issues (nausea, vomiting, diarrhea), and allergic reactions. Pegvaliase, in particular, can cause severe hypersensitivity reactions, including anaphylaxis. The trial for JNT-517, a potential new treatment, aims to assess its safety and tolerability, with a focus on monitoring similar adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Phenylketonuria (PKU) that modulate phenylalanine metabolism. Sapropterin dihydrochloride (Kuvan) is a synthetic form of the cofactor for phenylalanine hydroxylase, which helps reduce blood phenylalanine levels in some patients with PKU. Another approved treatment is pegvaliase-pqpz (Palynziq), an enzyme substitution therapy that breaks down phenylalanine. These treatments aim to manage phenylalanine levels in patients with PKU, similar to the investigational drug JNT-517, which is being studied for its potential effects on phenylalanine metabolism.

What other types of research exist?

Promising novel alternatives to JNT-517 for Phenylketonuria patients include Pegvaliase (an enzyme substitution therapy that breaks down phenylalanine) and gene therapy approaches targeting the PAH gene. Both are in advanced stages of research and show potential for effective management of PKU.

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JNT-517 for Phenylketonuria

Phase 1

Recruiting

Research Sponsored by Jnana Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

All Parts: Females of childbearing potential must agree to use 2 highly effective contraceptive methods

Parts A, B, and C: Body mass index (BMI) of 18-40 kg/m2 and total body weight >50 kg (110 lbs)

Must not have

All Parts: Any history of malignancy in the last 5 years, excluding non-melanoma skin cancer

All Parts: Current, recent, or suspected infection within 4 weeks of Screening of SARS-CoV-2/COVID-19

Timeline

Screening 3 weeks

Treatment Varies

Follow Up screening and days 1, 7, 14, 21, 28

Summary

This trial tests a new oral medication, JNT-517, for safety and tolerance. It involves healthy participants and people with phenylketonuria (PKU). Researchers aim to see if JNT-517 can safely reduce certain amino acids in people with PKU.

Who is the study for?

This trial is for healthy adults aged 18-55, and those with phenylketonuria (PKU) aged 18-65. Healthy participants must not smoke and have a BMI of 18-40 kg/m2. Women should agree to use two forms of contraception. PKU patients need a confirmed diagnosis and at least two plasma Phe levels >600 μM in the past year.

What is being tested?

The study tests JNT-517's safety, tolerability, dosage effects, and impact on urinary Phe in healthy individuals and those with PKU across four parts: single & multiple dose studies, bioavailability comparison between tablet/suspension forms with food effect analysis in healthy volunteers, and a placebo-controlled test in PKU patients.

What are the potential side effects?

Potential side effects are not detailed here but will be monitored throughout the trial phases focusing on any adverse reactions from taking JNT-517 or placebo as well as its overall tolerability during different dosing regimens.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I agree to use two effective birth control methods if I can have children.

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My BMI is between 18-40 and I weigh more than 110 lbs.

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I have been diagnosed with PKU and my genetic test confirms it.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not had any cancer except for non-melanoma skin cancer in the last 5 years.

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I haven't had COVID-19 or suspected COVID-19 in the last 4 weeks.

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I have a history of liver disease.

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I cannot take medicine by mouth.

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I am positive for hepatitis B, C, or HIV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ screening and days 1, 7, 14, 21, 28

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~screening and days 1, 7, 14, 21, 28

This trial's timeline: 3 weeks for screening, Varies for treatment, and screening and days 1, 7, 14, 21, 28 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of participants with treatment-emergent adverse events

Secondary study objectives

Changes in urinary amino acid levels

Comparison of AUC of JNT-517 in fed and fasted states

Comparison of Cmax of JNT-517 in fed and fasted states

+1 more

Trial Design

6Treatment groups

Experimental Treatment

Group I: JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C)Experimental Treatment2 Interventions

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.

Group II: JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C)Experimental Treatment2 Interventions

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.

Group III: JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C)Experimental Treatment2 Interventions

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.

Group IV: JNT-517 SAD (Part A)Experimental Treatment2 Interventions

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

Group V: JNT-517 PKU (Part D)Experimental Treatment2 Interventions

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

Group VI: JNT-517 MAD (Part B)Experimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo Tablet

2016

Completed Phase 3

~3600

Placebo Suspension

2014

Completed Phase 1

~110

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Phenylketonuria (PKU) treatments primarily focus on reducing phenylalanine levels in the blood to prevent neurotoxic effects. The most common treatments include a strict low-phenylalanine diet and the use of medical foods or supplements that provide essential nutrients without phenylalanine. Additionally, enzyme substitution therapy with phenylalanine ammonia-lyase (PAL) can help break down phenylalanine. Emerging treatments like JNT-517 potentially modulate phenylalanine metabolism, offering a pharmacological approach to manage phenylalanine levels more effectively. These treatments are vital for PKU patients to prevent cognitive impairment and other neurological issues associated with high phenylalanine levels.

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