AAV Gene Therapy Clinical Study in Adult Classic PKU (PHEdom)
ConditionPhenylketonurias
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-55
SponsorNGGT INC.
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 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Subjects with PKU that is not due to PAH mutation
Presence of anti-AAV8 neutralizing antibodies
Alanine aminotransferase (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
12 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 52 and during Year 1 to 52
Change from baseline in clinical laboratory values
Change in chemistry values including liver function tests, hematology and urinalysis.
Time frame
Baseline to Week 52 and during Year 1 to 53
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.
Time frame
Baseline to Week 52 and during Year 1 to 54
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.
Time frame
Baseline to Week 52 and during Year 1 to 5Secondary outcomes
1
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.
Time frame
Baseline to Week 52 and during Year 1 to 52
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.
Time frame
Baseline to Week 52 and during Year 1 to 53
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.
Time frame
Baseline to Week 52 and during Year 1 to 5 Source ClinicalTrials.gov