This is a single group Phase 1/Phase 2, 1-arm, open-label study with SAR444836, an adeno-associated virus (AAV) vector-mediated gene transfer of human phenylalanine hydroxylase (PAH), for the treatment of adult participants with phenylketonuria (PKU) on a chronic, stable diet. The purpose of the study is to evaluate the safety and efficacy of SAR444836 in reducing phenylalanine (Phe) levels and in the elimination of a Phe restricted diet. Participants will receive a one-time intravenous (IV) administration of SAR444836. The study is constituted of 2 separate parts: a dose escalation part, and a dose expansion part where subsequent participants will be administered a safe and effective dose level identified during the dose escalation part. In both study parts, clinical and laboratory assessments will be collected to: a) assess the incidence of adverse events, and b) evaluate the effect of SAR444836 on reductions in blood Phe levels and maintenance of these Phe levels after elimination of a Phe restricted diet. The study duration will be for a minimum duration of 5 years following SAR444836 administration, for each participant and includes a 6-week screening phase, a 96-week treatment follow-up period after SAR444836 administration, followed by an additional 3 years of long-term safety (and efficacy) monitoring. There will be a total of 47 study visits. Many study visits may occur as remote visits and be performed by a qualified in-home service provider. Actual study duration for an individual participant may be longer than 5 years due to the administration of SAR444836 to participants in Stage 1A in a serial fashion, the duration of the screening period, and/or other factors such as delays in scheduling study visits.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Infusion pump, intravenous infusion (IV)
University of California San Francisco- Site Number : 8400007
San Francisco, California, United States
Children's Hospital IMD Clinic- Site Number : 8400015
Aurora, Colorado, United States
University of Florida-Genetics- Site Number : 8400010
Gainesville, Florida, United States
UHCMC- Site Number : 8400014
Cleveland, Ohio, United States
UPMC Children's Hospital of Pittsburgh-4401 Penn Ave- Site Number : 8400018
Pittsburgh, Pennsylvania, United States
Medical University of SC- Site Number : 8400004
Charleston, South Carolina, United States
University of Texas- Site Number : 8400002
Houston, Texas, United States
Investigational Site Number : 0320002
Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina
Hospital de Clinicas de Porto Alegre - HCPA- Site Number : 0760001
Porto Alegre, Rio Grande do Sul, Brazil
Investigational Site Number : 3760001
Tel Litwinsky, Israel
...and 1 more locations
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: From Baseline to Week 260
Proportion of participants with sustained plasma level of Phe<360 μmol/L for ≥4 weeks without dietary Phe restriction at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Change from baseline in plasma level of Phe at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Change from baseline in dietary protein intake at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Proportion of participants with sustained plasma level of Phe <600 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Proportion of participants with sustained plasma level of Phe <120 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Change from baseline in plasma Phe: Tyr ratio at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Number of participants with abnormal laboratory chemistry values
Time frame: From Baseline to Week 96
Assessment of the duration of viral vector shedding of SAR444836 in sampling of urine, saliva, and semen at 4-week intervals following SAR444836 administration
Time frame: From Baseline to Week 96
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