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

NCT ID: NCT06332807

Last Updated: 2025-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-10

Study Completion Date

2030-12-30

Brief Summary

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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

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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

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Phenylketonurias

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NGGT002

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.

Group Type EXPERIMENTAL

NGGT002

Intervention Type GENETIC

adeno-associated viral vector with human phenylalanine hydroxylase gene

Interventions

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NGGT002

adeno-associated viral vector with human phenylalanine hydroxylase gene

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. 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).
3. Adults aged 18-55 at the time of informed consent
4. Subjects intolerant or unresponsive to available medical therapies, such as Kuvan, Playnzip, etc.
5. 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).
6. At least 1 documented measurements of Phe ≥ 600 μmol/L while on usual diet in the preceding 6 months.
7. Subjects are willing to record their diet and follow the instruction of dietitians during the trial.
8. Willingness and capable per Investigator opinion to comply with study procedures and requirements.
9. 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

1. Subjects with PKU that is not due to PAH mutation
2. Presence of anti-AAV8 neutralizing antibodies
3. 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
4. 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.
5. Contraindications to corticosteroid use or possible deterioration of corticosteroid use assessed and determined by the Investigator.
6. 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).
7. 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.
8. All types of past and current malignancy
9. Imaging (liver ultrasound) proved the existence of Liver fibrosis, liver cirrhosis and other serious liver diseases
10. Severe diseases in the cardiovascular, respiratory, digestive tract, endocrine, kidney, blood, nervous, mental and other systems before screening.
11. History of allergy to Albumin (Human)
12. The subjects who have Substance Use Disorder (for example alcohol, heroin, amphetamine, etc)
13. The subjects who have received any gene therapy in the past, regardless of when it was administered.
14. The subjects who have received any investigational treatment and took drugs within 3 months before screening (or 5 half-lives, if longer)
15. Subjects with elevated circulating serum alpha-fetoprotein (AFP)
16. 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.
17. Subjects who are presently on available medications for the treatment of PKU, such as Kuvan, Palynziq, etc.
18. Subjects who weight over 120 Kg
19. Subjects who consume too much natural protein (\>2 g/Kg body weight/day) in their daily diet
20. Breastfeeding subjects will not be included in the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NGGT INC.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Children's Hospital of Orange County Hospital

Orange, California, United States

Site Status RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

Atlantic Health System

Morristown, New Jersey, United States

Site Status RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

University or Texas, Southwestern medical Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Study Contact

Role: CONTACT

916-337-9683

Jinpeng Zhu

Role: CONTACT

8651283912888

Facility Contacts

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Cheryl Willis

Role: primary

714-509-4225 ext. 14225

Carrie Gibson

Role: primary

651-274-6024

Claudia Rohan

Role: primary

973-829-4581

Angela Riemenschneider

Role: primary

412-692-5232

Juana Luevano

Role: primary

214.645-7411

Other Identifiers

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NGGT002-P-2301

Identifier Type: -

Identifier Source: org_study_id

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