Safety and Efficacy Study of NGGT002 in Adult Patients With Phenylketonuria
ConditionPhenylketonurias
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-55
SponsorNGGT (Suzhou) Biotechnology Co., Ltd.
About this trial
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 a 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Voluntarily participating in the study and signing the informed consent form;
Gender is not limited; patients must carry biallelic pathogenic or likely pathogenic variants in the PAH gene;
Adult patients aged 18 to 55 years;
In the past 24 months, at least two blood Phe concentrations have been ≥600 μmol/L (10 mg/dL), with at least one of these measurements taken within 6 months prior to the screening period;
Disqualifiers
Presence of anti-AAV8 neutralizing antibodies（≥1:5）
Participants whose disease is well-controlled with existing therapies, such as those currently receiving medications like Sapropterin Dihydrochloride tablets, Pegvaliase-pqpz, etc. (excluding participants who have previously received the above-mentioned drug therapies but did not respond, and have been off treatment for more than 6 weeks);
Alanine Transaminase (ALT) > 1.5×ULN and/or Aspartate Aminotransferase (AST) > 1.5×ULN
Alkaline Phosphatase (ALP) > 1.5×ULN
Trial design
Design model
Single group
Treatments tested in this trial
NGGT002
Geneticadeno-associated viral vector with human phenylalanine hydroxylase gene
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: NGGT002Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline to Week 522
Change from baseline in average Plasma Phe Concentration at Weeks 12, 28 and 52.
To evaluate the efficacy of intravenous infusion of NGGT002 in adults with classic PKU, as assessed by the change from baseline in mean plasma Phe concentration at Weeks 12, 28, and 52.
Time frame
Baseline, Week 12, Week 28, Week 52Secondary outcomes
1
Incidence of participants in each dose cohort with a plasma Phe concentration ≤360 μmol/L (6 mg/dL) at Weeks 12, 28, and 52 following NGGT002 administration.
Participants achieving a sustained plasma Phe concentration ≤360 μmol/L (6 mg/dL) at Week 12, Week 28, Week 52 post dose.
Time frame
Week 12, Week 28, Week 522
Time to first achievement of a plasma Phe concentration ≤360 μmol/L and duration of maintenance of plasma Phe concentration at ≤360 μmol/L in each dose cohort following NGGT002 administration.
Time (weeks) to first achievement of a blood Phe ≤ 360 μmol/L and the duration(weeks) of Phe ≤ 360 μmol/L in each dose group following NGGT002 administration
Time frame
Week 523
Change from baseline in daily Phe intake (mg/day) and total natural protein intake (g/day) at Weeks 28 and 52.
Participants achieving a change from baseline in Phe and nature protein intake at Week 28, Week 52 post dose.
Time frame
Baseline, Week 28, Week 524
Change from baseline in Phenylketonuria Quality of Life Questionnaire (PKU-QOL) score at Weeks 28 and 52.
Change from baseline in PKU-QOL score at Week 28, Week 52 following dosing.
Time frame
Baseline, Week 28, Week 52Sponsors and contacts
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Source ClinicalTrials.gov