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

NCT ID: NCT05972629

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-07
• Study Completion Date: 2030-04-02

Brief Summary

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.

Conditions

Phenylketonuria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SAR444836

Participants will receive a single dose of SAR444836 on Day 1

Group Type: EXPERIMENTAL

SAR444836

Intervention Type: DRUG

Infusion pump, intravenous infusion (IV)

Interventions

SAR444836

Infusion pump, intravenous infusion (IV)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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

Investigational Site Number : 7920001

Ankara, , Turkey (Türkiye)

Countries

United States; Argentina; Brazil; Israel; Turkey (Türkiye)

Related Links

https://sanofi.trialsummaries.com/Study/StudyDetails?id=25223&tenant=MT_SNY_9011

DFI17545 Plain Language Results Summary

Other Identifiers

U1111-1271-1293

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-501200-98

Identifier Type: REGISTRY

Identifier Source: secondary_id

DFI17545

Identifier Type: -

Identifier Source: org_study_id