A Phase 1/Phase 2 Open-label Study to Evaluate the Safety, Tolerability, and Efficacy of a Single Intravenous Administration of SAR444836 in Adult Participants With Phenylketonuria

Inclusion criteria

• Adult males, and females of non-childbearing potential, 18-65 years of age at the time of informed consent.
• Participants must have uncontrolled classical PKU due to PAH deficiency (despite Phe-restricted dietary management or Palynziq) in the judgement of the Investigator.
• Two historical plasma Phe values ≥ 600 μmol/L in the preceding 12 months while on Phe restricted diet therapy. Two plasma Phe values ≥ 600 μmol/L drawn at least 72 hours apart during the screening period while on Phe restricted diet therapy in the absence of an acute illness.
• Participant has the ability and willingness to maintain their present diet for the duration of the Post-treatment Follow-up Phase (through Week 96), unless otherwise directed as per protocol
• Body mass index (BMI) ≤ 35 kg/m2
• Willingness to use effective methods of contraception.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria

• Presence of neutralizing antibodies against the AAV SNY001 capsid
• Abnormal liver function laboratory testing evidenced by alanine aminotransferase (ALT)>1.5X upper limit normal (ULN), aspartate transaminase (AST)>1.5X ULN, alkaline phosphatase >1.5X ULN, Total and direct bilirubin >1.5X ULN (bilirubin levels above the laboratory's normal range are acceptable in individuals with a documented history or laboratory evidence of Gilbert's Disease)
• Any significant underlying liver disease or any of the following documented diagnoses, indicative of significant underlying liver disease:

• Portal hypertension; or
• Splenomegaly; or
• Hepatic encephalopathy
• Serum albumin measurement below the lower limit of normal of the laboratory OR AST-to-Platelet Ratio Index > 1.0
• Serum creatinine >1.5X ULN
• Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
• Screening laboratory testing demonstrating any of the following:

• HIV; or
• active or prior hepatitis B virus (HBV) infection defined as positive test for hepatitis B surface antigen (HBsAg) or positive test for hepatitis B core antibody (total HBcAb) or detectable HBV DNA; or
• active hepatitis C virus (HCV) infection defined as positive test for hepatitis C antibody followed by detectable HCV RNA or if a participant is presently receiving (or has received within 6 months prior to screening) anti-viral therapy for hepatitis C
• Clinically significant, active bacterial, viral, fungal, or parasitic infection (based on Investigator's judgement)

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.