A Phase 3 Study of JNT-517 in Participants with Phenylketonuria
EU CTIS ID: 2024-519554-37-00
What this study is testing
To assess the efficacy of JNT-517 at the high dose twice daily (BID) compared with placebo during 6 weeks of double-blind treatment (Period 1)
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Males and females ≥12 years of age at Screening (Participants aged 12 to 17 years of age will not be enrolled in the Czech Republic.)
- If biologically male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 must be highly effective, from Day 1 until at least 30 days after the last study drug administration and must refrain from donating sperm during the course of the study and for 30 days after the last dose of the study drug NOTE: No restrictions are required for biological males who have undergone a documented vasectomy at least 4 months prior to Screening. If the vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants.
- Participants with psychiatric illness must be well-controlled for the last 6 months prior to the Screening visit and if on medication, on stable medications for the last 3 months.
- Capable of giving signed informed consent or parent/legal guardian to provide informed consent and pediatric participant to give assent and be able to comply with study procedures.
- Diagnosis of PKU (ie, phenylalanine hydroxylase [PAH] deficiency) by either molecular testing or biochemical criteria consistent with the applicable regional guidelines.
- Average of at least 3 plasma Phe levels (after ≥4-hour fast) during Screening period of ≥360 µmol/L
You likely can't join if
- Any acute or uncontrolled 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
- Any history of significant liver disease
- Any prior cataract surgery or more than minimal cataracts observed during the Screening ophthalmologic examination. Minimal cataracts are defined as changes similar to lens opacities classification system III (LOCS III), lens grade C1, N1 or P1.
- Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion
- Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 by 2021 Chronic Kidney Disease Epidemiology (CKD-Epi) Collaboration formula (participants aged ≥ 18 years of age) or by Chronic Kidney Disease Under 25 (CKiD U25) formula (participants aged 12 to 17 years of age).
- Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer). For gene therapy or editing trials, participants must have received the intervention >6 months prior to Screening visit and with stable plasma Phe in the past 2 months prior to Screening visit
See the full eligibility criteria
Who can join
- Males and females ≥12 years of age at Screening (Participants aged 12 to 17 years of age will not be enrolled in the Czech Republic.)
- If biologically male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 must be highly effective, from Day 1 until at least 30 days after the last study drug administration and must refrain from donating sperm during the course of the study and for 30 days after the last dose of the study drug NOTE: No restrictions are required for biological males who have undergone a documented vasectomy at least 4 months prior to Screening. If the vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants.
- Participants with psychiatric illness must be well-controlled for the last 6 months prior to the Screening visit and if on medication, on stable medications for the last 3 months.
- Capable of giving signed informed consent or parent/legal guardian to provide informed consent and pediatric participant to give assent and be able to comply with study procedures.
- Diagnosis of PKU (ie, phenylalanine hydroxylase [PAH] deficiency) by either molecular testing or biochemical criteria consistent with the applicable regional guidelines.
- Average of at least 3 plasma Phe levels (after ≥4-hour fast) during Screening period of ≥360 µmol/L
- Not on pegvaliase within 4 weeks prior to Screening
- If on sapropterin or large neutral amino acids, such as PheBloc®, NeoPhe®, and PreKunil® at Screening, must be on a stable dose 4 weeks prior to Screening and for the entire study duration.
- Willing and able to maintain a stable diet in Phe and total protein (intact protein and medical food protein) and able to adjust diet through the duration of the study according to the Dietary Management Guidelines
- Body weight ≥12.5 kg.
- If biologically female of childbearing potential: a. Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1 b. Must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 must be highly effective, from Screening until at least 30 days after the last study drug administration c. If taking estrogen- or progesterone-based oral contraceptives, must agree to use 2 other methods of contraception, where at least 1 must be highly effective, or must agree to sexual abstinence during the study d. Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
- If a biologically female not of childbearing potential or postmenopausal, defined as follows: a. Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy). b. Has had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone (FSH) testing. c. Has not achieved menarche (has not had first menstrual period). If a female achieves menarche during the study, she will need to follow the contraception requirement for females of childbearing potential
- Not on sepiapterin within 2 weeks prior to Screening.
What rules you out
- Any acute or uncontrolled 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
- Any history of significant liver disease
- Any prior cataract surgery or more than minimal cataracts observed during the Screening ophthalmologic examination. Minimal cataracts are defined as changes similar to lens opacities classification system III (LOCS III), lens grade C1, N1 or P1.
- Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion
- Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 by 2021 Chronic Kidney Disease Epidemiology (CKD-Epi) Collaboration formula (participants aged ≥ 18 years of age) or by Chronic Kidney Disease Under 25 (CKiD U25) formula (participants aged 12 to 17 years of age).
- Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer). For gene therapy or editing trials, participants must have received the intervention >6 months prior to Screening visit and with stable plasma Phe in the past 2 months prior to Screening visit
- Alcohol consumption more than 1 alcoholic drink per day starting 5 days prior to dosing and/or unwilling to limit to 1 alcoholic drink per day until after the 6-month study visit.
- History of drug/alcohol abuse in the last year
- QT interval corrected for heart rate using Fridericia’s formula > 450 msec for adult male participants, > 470 msec for adult female participants, or > 450 msec for pediatric participants regardless of biological sex.
- Previous exposure to repinatrabit.
- Unwilling to avoid intentional weight loss throughout the study through methods such as calorie restriction or pharmacotherapy.
- Use of any medications that are inhibitors or inducers of cytochrome P450 isoenzyme 3A4 (CYP3A4) or inhibitors of the transporter P-glycoprotein (P-gp) within 4 weeks prior to randomization and unwilling and/or unable to avoid these medications throughout the treatment duration (Appendix A)
- Use of any medications that are a substrates of breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, MATE2-K, organic anion transporter 3 (OAT3), or CYP3A4 within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration (Appendix A)). CYP3A4 substrates may be allowed if reduction in exposure is not expected to impact safety of the participant after consultation with the Medical Monitor.
- Current, recent, or suspected active viral or bacterial infection within 2 weeks prior to and during the Screening Period
- Unable to tolerate oral medication or have a condition that would interfere with the absorption of JNT-517
- Allergy to JNT-517 or any component of the investigational product
- Any of the following laboratory values at the Screening visit. -Alanine aminotransferase or aspartate aminotransferase values >1.5× the upper limit of normal (ULN) -Total bilirubin ˃ULN unless history of Gilbert Syndrome and then total bilirubin >4 mg/dL is exclusionary -Hemoglobin <10.0 g/dL (<100.0 g/L) -White blood cell count >ULN -Platelets <150 × 109/L (<150,000/mm3).
- Positive for hepatitis B or C or human immunodeficiency virus
- Any history of malignancy of any organ system (other than non-melanoma skin cancer or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
The study team makes the final eligibility decision.
Where it's taking place
- Czechia
- Italy
- Spain
- Netherlands
- Poland
- Germany
- Turkey
- Japan
- Australia
- Canada
- United States
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Czechia; Italy; Spain; Netherlands; Poland; Germany and 6 more locations. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from EU CTIS. The study team decides eligibility, and your own doctor gives medical advice.