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

Launched by SANOFI · Jul 31, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called SAR444836 for adults with a condition known as phenylketonuria (PKU). PKU is a genetic disorder that affects the body’s ability to process a substance called phenylalanine (Phe), which can build up in the blood and cause serious health problems. The goal of this study is to see if a single intravenous (IV) dose of SAR444836 can safely lower the levels of Phe in the blood and potentially allow participants to stop following a strict Phe-restricted diet.

To be eligible for this trial, participants must be adults aged 18 to 65 who have uncontrolled PKU, meaning their Phe levels remain high despite following a special diet. They should also be willing to maintain their current diet during the study. Participants will receive the treatment and then be monitored over approximately two years, with regular visits to check their health and Phe levels. This study aims to help find out if this new treatment can make a difference for people living with PKU.

Gender

ALL

Eligibility criteria

• 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.