ClinicalTrials.gov record NCT06332807

AAV Gene Therapy Clinical Study in Adult Classic PKU (PHEdom)

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 6, 2026

An Open-Label, Multiple-Center, Phase I/II Dose Escalation Study for the Safety and Efficacy of NGGT002 in Adults With Classic Phenylketonuria

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 1/2A study that combines safety and dose-finding (phase 1) with a first look at whether the treatment has an effect (phase 2).
Age18 years old to 55 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Phase 1/2 open-label study testing a one-time intravenous dose of NGGT002 gene therapy in adults. It is for adults (18–55) with classic PKU due to severe PAH deficiency. Participants receive one infusion and are followed for safety and blood phenylalanine for up to 5 years.

What it is studying. The study is testing the safety and effects of a single intravenous administration of NGGT002, an AAV8-based gene therapy delivering a working PAH gene, in adults with classic PKU. It measures adverse events, clinical labs (including liver tests), vital signs, and plasma phenylalanine levels over time to assess tolerability and biological effect.

What the researchers hope to learn. To evaluate the safety and tolerability of a single IV dose of NGGT002 and to collect data on how the treatment affects blood phenylalanine levels. Secondary goals include measuring changes in protein intake and PKU-specific quality of life, and monitoring longer-term safety over 1–5 years.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

This is a Phase 1/2, open-label, multiple-center, dose escalation and cohort expansion study to evaluate the safety and efficacy of NGGT002 in adult subjects with classic Phenylketonuria (PKU). NGGT002 is an rAAV8 based vector carrying a functional copy of the human PAH gene. Participants will receive a single administration of NGGT002 and will be followed for safety and efficacy for 5 years.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Genetic
  • NGGT002

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Is willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures; a legally authorized representative may provide written consent and assent may be requested.
  • Male and female subjects with diagnosis of classic PKU, a condition characterized by severe PAH deficiency with confirmed PAH mutations predicted with no residual enzyme activity. A list of PAH mutations for classic PKU based on in vitro PAH activity (Himmelreich et al., 2018) and the genotype-phenotype correlation (Garbade et al., 2019) can be found in BIOPKU genotypes database (http://www.biopku.org/pah).
  • Adults aged 18-55 at the time of informed consent
  • Subjects intolerant or unresponsive to available medical therapies, such as Kuvan, Playnzip, etc.
  • Subjects who have been on medications, such as Kuvan, Palynziq, etc but have come off for medical reasons or the patient's decision at least 28 days prior to signing the consent form (Subjects who have good disease control on these existing therapies will not be included in this study).
  • At least 1 documented measurements of Phe ≥ 600 μmol/L while on usual diet in the preceding 6 months.
  • Subjects are willing to record their diet and follow the instruction of dietitians during the trial.
  • Willingness and capable per Investigator opinion to comply with study procedures and requirements.
  • Women of child bearing potential must be confirmed as negative non pregnant subjects by blood pregnancy test from day -28 to day 0. Subjects must agree to use a highly effective form of contraception from the time of NGGT002 administration until a minimum of 1 year after NGGT002 administration, and for male subjects, a minimum of 3 consecutive semen samples are negative for AAV8 after administration of NGGT002. Highly effective birth control methods include:
  • documented vasectomy or permanent sterilization
  • condom
  • combined (estrogen and progestogen-containing) hormonal contraception (oral, intravaginal or transdermal)
  • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)
  • intrauterine device
  • intrauterine hormone-releasing system
  • sexual abstinence is acceptable only as true abstinence and when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, hypothermal, post-ovulation) is not acceptable as a form of abstinence.

Exclusion criteria

  • Subjects with PKU that is not due to PAH mutation
  • Presence of anti-AAV8 neutralizing antibodies
  • Prior to dosing, subjects exceed the limit of any of the following liver function and hematology tests in two consecutive blood laboratory tests:
  • Alanine aminotransferase (ALT) >1.5×ULN and/or aspartate aminotransferase (AST) >1.5×ULN
  • Alkaline phosphatase (ALP) >1.5×ULN
  • Total bilirubin (TBil) >1.5×ULN, direct bilirubin >1.5×ULN
  • International normalized ratio (INR) > 1.5
  • Blood creatinine (Scr) >1.5×ULN
  • Hematology values outside of the normal range (Hemoglobin <110 g/L (male), <100 g/L (female), white blood cell <3.0×10\^9/L, neutrophil <1.5×10\^9/L, platelet <100×10\^9/L)
  • Hemoglobin A1c >6% or fasting glucose >6.1 mmol/L
  • At the time of screening, abnormal vital signs (i.e. Temperature<36.3°C or >37.4°C; Blood pressure<100/60 mmHg or >130/80 mmHg; heart rate <60/min or>100/min; respiratory rate <12/min or >18/min; oxygen saturation<95%), physical examination, laboratory tests, or other related results that have clinical significance, and the researchers believe they are unsuitable for enrollment.
  • Contraindications to corticosteroid use or possible deterioration of corticosteroid use assessed and determined by the Investigator.
  • Active infection with hepatitis A virus (HAV ribonucleic acid [RNA] positive), active or occult hepatitis B virus infection (positive HBV-DNA or anti-HBc positive with negative hBsAg, HBV surface antigen), active infection with hepatitis C virus (HCV RNA positive), infection with the human immunodeficiency virus (HIV) as measured by antibodies to HIV-1 and HIV-2, active or latent infection with tuberculosis (TB) measured by Quantiferon Gold, infection with syphilis by rapid plasma regainn (RPR) and/or serum syphilis antibody, treponema pallidum particle agglutination (TPPA).
  • Subjects with history of liver disease such as clinically significant steatosis, fibrosis, non-alcoholic steatohepatitis (NASH) and cirrhosis, biliary disease within 6 months of informed consent; except for Gilbert's syndrome.
  • All types of past and current malignancy
  • Imaging (liver ultrasound) proved the existence of Liver fibrosis, liver cirrhosis and other serious liver diseases
  • Severe diseases in the cardiovascular, respiratory, digestive tract, endocrine, kidney, blood, nervous, mental and other systems before screening.
  • History of allergy to Albumin (Human)
  • The subjects who have Substance Use Disorder (for example alcohol, heroin, amphetamine, etc)
  • The subjects who have received any gene therapy in the past, regardless of when it was administered.
  • The subjects who have received any investigational treatment and took drugs within 3 months before screening (or 5 half-lives, if longer)
  • Subjects with elevated circulating serum alpha-fetoprotein (AFP)
  • Other conditions that the Investigators deemed inappropriate for enrollment, such as PKU severe comorbidities and conditions (i.e. renal insufficiency or kidney failure, osteoporosis, anemia, acid reflux or gastro-esophageal ulcer, major depression, epilepsy, etc.), which may be deteriorated with the potential risks of NGGT002.
  • Subjects who are presently on available medications for the treatment of PKU, such as Kuvan, Palynziq, etc.
  • Subjects who weight over 120 Kg
  • Subjects who consume too much natural protein (>2 g/Kg body weight/day) in their daily diet
  • Breastfeeding subjects will not be included in the study

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Detailed description from the registry

This study will evaluate the safety and efficacy of NGGT002 gene therapy with two dose cohorts in adult subjects with diagnosis of classic PKU, a condition characterized by severe PAH deficiency with no residual enzyme activity. NGGT002 will be administered through intravenous infusion. In Part 1 of the study, subjects will receive NGGT002 at the low dose. Dosing of the first 3 subjects will be staggered. Following evaluation of data from the first 3 subjects, a decision can be made to either escalate to the high dose level or expand the low dose cohort with additional 3 subjects. Upon completion of Part 1 study, based on the evaluation of and safety and efficacy, the study may be stopped or proceed to Part 2. In Part 2, the same process will be conducted with 3 -6 subjects dosed at the high dose.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants receive a single intravenous infusion of NGGT002 (one dose, low or high dose) and then have regular follow-up visits for safety and efficacy for up to 5 years. Visits include blood tests (including liver tests and plasma Phe), ECGs, physical exams, and questionnaires; participants must record their diet and follow dietitian guidance. Women will have pregnancy tests and must use specified contraception; men will provide semen samples for AAV8 testing until required negative results. The study includes close medical monitoring for adverse events throughout follow-up.

How the study is structured. Open-label, non-randomized Phase 1/2 dose-escalation with a single treatment group. There are two dose cohorts (low and high); initial subjects in each cohort are dosed in a staggered manner with possible cohort expansion. Each participant receives one IV infusion of NGGT002 and is followed for safety and efficacy assessments for up to 5 years. No masking is used.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on phenylketonuria

Clinical trials38 trials listed for phenylketonuriaEvery trial the registry lists for phenylketonuria, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in phenylketonuria researchLatest monthly update: September 2026. Includes: Diet supply gaps. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Jan 10, 2025
Primary completion
Dec 30, 2030 (estimated)
Study completion
Dec 30, 2030 (estimated)
Target enrollment
12 participants (estimated)
Last updated on registry
Aug 18, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
NGGT INC.

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (5)

Terms used on this page · explanations by MedicalUpdates.ai

open-label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
dose escalation
Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
cohort
A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
legally authorized representative
A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
assent
A child's or dependent adult's agreement to take part, given alongside the formal consent of a parent or legal representative.
ULN
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
enrollment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
Contraindications
A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
corticosteroid
Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
before screening
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
investigational
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
5 half-lives
The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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