PhenylketonuriasPhase 1/2NCT06332807
AAV Gene Therapy Clinical Study in Adult Classic PKU (PHEdom)
A Phase 1/2 study testing NGGT002 in people with Phenylketonurias, run by NGGT INC. at 5 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Phenylketonurias
- What is being tested?
- NGGT002
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 5 sitesUnited States
- Study dates
- 10 Jan 2025to 30 Dec 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University or Texas, Southwestern medical Center
Dallas, Texas, 75390
Juana Luevano, 214.645-7411, juana.luevano@utsouthwestern.edu
Markey McNutt, MD, PhD
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55454
Carrie Gibson, 651-274-6024, Carrie.Gibson@fairview.org
Chester Whitley, MD
- Recruiting
Atlantic Health System
Morristown, New Jersey, 07960
Claudia Rohan, 973-829-4581, Claudia.Rohan@atlantichealth.org
Darius Adams, MD
- Recruiting
Children's Hospital of Orange County Hospital
Orange, California, 92868
Julia Becerra, 714-509-4310 ext. 14225, julia.becerra@choc.org
Richard Chang, MD
- Recruiting
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15224
Angela Riemenschneider, 412-692-5232, Angela.Riemenschneider@chp.edu
Gerard Vockley, MD,PhD
About this study
Official title: An Open-Label, Multiple-Center, Phase I/II Dose Escalation Study for the Safety and Efficacy of NGGT002 in Adults With Classic Phenylketonuria
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.
Read the detailed description
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.
- Conditions
- Phenylketonurias
- Being tested
- NGGT002
- Keywords
- PAH, Phenylalanine, Phenylalanine Hydroxylase
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NGGT002Genetic
adeno-associated viral vector with human phenylalanine hydroxylase gene
| Study group | Role | What they receive |
|---|---|---|
| NGGT002 | Experimental | Low dose and high dose group:
Six to twelve patients will be enrolled into two cohorts at two dose levels. The safety of this study can be ensured by selecting the highest dose under the No Observed Adverse Effect Level (NOAEL) doses observed in preclinical toxicology studies. Receives: Genetic: NGGT002 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of Adverse Events (AEs)
Incidence and severity of AEs, including serious AEs (SAEs) as assessed by CTCAE v5.0 of a single administration of NGGT002.
Measured: Baseline to Week 52 and during Year 1 to 5
Change from baseline in clinical laboratory values
Change in chemistry values including liver function tests, hematology and urinalysis.
Measured: Baseline to Week 52 and during Year 1 to 5
Change from baseline in 12-lead electrocardiograms (ECGs), vital signsand physical examinations
Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs and physical examinations.
Measured: Baseline to Week 52 and during Year 1 to 5
Change from baseline in Plasma Phe Concentration
To evaluate the efficacy in change of plasma Phe concentration of IV infusion of NGGT002 in adults with classic PKU at Week 12, Week 28, Week 52 and during Year 1 to 5.
Measured: Baseline to Week 52 and during Year 1 to 5
Secondary outcomes (3)
Incidence of sustained plasma Phe concentration of ≤360 μmol/L (6 mg/dL) at Week 12, Week 28, Week 52 and during Year 1 to 5 post dose
Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L (6 mg/dL) at Week 12, Week 28, Week 52 and during Year 1 to 5 post dose.
Measured: Baseline to Week 52 and during Year 1 to 5
Change from baseline in total protein intake at at Week 28, Week 52 and during Year 1 to 5 post dose
Subject achieving a change from baseline in total protein intake at Week 28, Week 52 and during Year 1 to 5 post dose.
Measured: Baseline to Week 52 and during Year 1 to 5
Change in Phenylketonuria Quality of Life Questionnaire (PKU-QOL)
Change in PKU-QOL at Week 28, Week 52 and during Year 1 to 5 post dose.
Measured: Baseline to Week 52 and during Year 1 to 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2024
- Study start10 Jan 2025
- Primary completion30 Dec 2030 (estimated)
- Study completion30 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NGGT INC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06332807
- Sponsor's protocol ID
- NGGT002-P-2301
- Status last verified
- Aug 2026
- First submitted
- 7 Feb 2024
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multiple-Center, Phase I/II Dose Escalation Study for the Safety and Efficacy of NGGT002 in Adults With Classic Phenylketonuria
- ClinicalTrials.gov ID
- NCT06332807
- Acronym / sponsor ID
- NGGT002-P-2301
- Conditions
- Phenylketonurias
- Keywords
- PAH, Phenylalanine, Phenylalanine Hydroxylase
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- NGGT INC.Industry (pharma, biotech, devices)
- Study start
- 10 Jan 2025 (actual)
- Primary completion
- 30 Dec 2030 (estimated)
- Study completion
- 30 Dec 2030 (estimated)
- First posted
- 27 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NGGT002 | Experimental | Genetic: NGGT002Low dose and high dose group: Six to twelve patients will be enrolled into two cohorts at two dose levels. The safety of this study can be ensured by selecting the highest dose under the No Observed Adverse Effect Level (NOAEL) doses observed in preclinical toxicology studies. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- 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).
Key exclusion criteria (27 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NGGT002adeno-associated viral vector with human phenylalanine hydroxylase gene | Genetic | NGGT002 |
Primary outcome
Incidence and severity of Adverse Events (AEs)
Time frame: Baseline to Week 52 and during Year 1 to 5
Incidence and severity of AEs, including serious AEs (SAEs) as assessed by CTCAE v5.0 of a single administration of NGGT002.
Change from baseline in clinical laboratory values
Time frame: Baseline to Week 52 and during Year 1 to 5
Change in chemistry values including liver function tests, hematology and urinalysis.
Change from baseline in 12-lead electrocardiograms (ECGs), vital signsand physical examinations
Time frame: Baseline to Week 52 and during Year 1 to 5
Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs and physical examinations.
Change from baseline in Plasma Phe Concentration
Time frame: Baseline to Week 52 and during Year 1 to 5
To evaluate the efficacy in change of plasma Phe concentration of IV infusion of NGGT002 in adults with classic PKU at Week 12, Week 28, Week 52 and during Year 1 to 5.
3 secondary outcomes
Incidence of sustained plasma Phe concentration of ≤360 μmol/L (6 mg/dL) at Week 12, Week 28, Week 52 and during Year 1 to 5 post dose
Time frame: Baseline to Week 52 and during Year 1 to 5
Change from baseline in total protein intake at at Week 28, Week 52 and during Year 1 to 5 post dose
Time frame: Baseline to Week 52 and during Year 1 to 5
Change in Phenylketonuria Quality of Life Questionnaire (PKU-QOL)
Time frame: Baseline to Week 52 and during Year 1 to 5
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NGGT002 in people with Phenylketonurias, run by NGGT INC. at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Contact (916-337-9683, phedom@nggtbio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of Adverse Events (AEs) (time frame: Baseline to Week 52 and during Year 1 to 5). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.