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

NCT06332807 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NGGT002-P-2301
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

Brief 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. Participants will receive a single administration of NGGT002 and will be followed for safety and efficacy for 5 years.

Conditions

Phenylketonurias

Keywords

PAH; Phenylalanine; Phenylalanine Hydroxylase

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  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

  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

  Baseline to Week 52 and during Year 1 to 5

• Change in Phenylketonuria Quality of Life Questionnaire (PKU-QOL)

  Baseline to Week 52 and during Year 1 to 5

Study Arms (1)

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.

Genetic: NGGT002

Interventions

NGGT002 GENETIC

adeno-associated viral vector with human phenylalanine hydroxylase gene

NGGT002

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NGGT INC.: lead

Study Sites (5)

Children's Hospital of Orange County Hospital

Orange, California, 92868, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55454, United States

RECRUITING

Atlantic Health System

Morristown, New Jersey, 07960, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

University or Texas, Southwestern medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Study Contact

CONTACT

916-337-9683; phedom@nggtbio.com

Jinpeng Zhu

CONTACT

8651283912888; jpzhu@nggtbio.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2024
• First Posted: March 27, 2024
• Study Start: January 10, 2025
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2030
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)