Evaluating a new gene therapy for adults with phenylketonuria

A Phase 1/Phase 2, Open-label, Dose-escalation, and Dose Expansion Study to Evaluate the Safety, Tolerability, and Efficacy of SAR444836, an Adeno-associated Viral Vector-mediated Gene Transfer of Human Phenylalanine Hydroxylase, in Adult Participants With Phenylketonuria

This study is testing a new gene therapy for adults with phenylketonuria to see if it can lower their blood phenylalanine levels and help them stop following a special diet.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Sanofi (Industry-sponsored)
• Locations: 10 sites (San Francisco, California and 9 other locations)
• Trial ID: NCT05972629 on ClinicalTrials.gov

What this trial studies

This study investigates the safety, tolerability, and efficacy of SAR444836, a gene therapy designed to treat adults with phenylketonuria (PKU) by delivering a functional copy of the phenylalanine hydroxylase (PAH) gene. Participants will receive a single intravenous administration of SAR444836, and the study consists of two parts: a dose escalation phase to determine the optimal dose and a dose expansion phase to further evaluate its effects. The primary focus is on reducing blood phenylalanine levels and potentially allowing participants to eliminate their Phe-restricted diet. Clinical and laboratory assessments will monitor adverse events and the therapy's impact on phenylalanine levels over time.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with uncontrolled classical PKU despite dietary management.

Not a fit: Patients who have well-controlled PKU or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve the quality of life for patients with PKU by reducing their reliance on a strict dietary regimen.

How similar studies have performed: While gene therapies for PKU are still emerging, similar approaches have shown promise in preliminary studies, indicating potential for success.

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.

Where this trial is running

San Francisco, California and 9 other locations

• University of California San Francisco - Parnassus Heights- Site Number : 8400007 — San Francisco, California, United States (Recruiting)
• Children's Hospital Colorado - Aurora- Site Number : 8400015 — Aurora, Colorado, United States (Recruiting)
• University of Florida College of Medicine- Site Number : 8400010 — Gainesville, Florida, United States (Recruiting)
• University Hospitals Cleveland Medical Center- Site Number : 8400014 — Cleveland, Ohio, United States (Recruiting)
• UPMC Children's Hospital of Pittsburgh- Site Number : 8400018 — Pittsburgh, Pennsylvania, United States (Recruiting)
• Medical University of South Carolina - Charleston - Jonathan Lucas Street- Site Number : 8400004 — Charleston, South Carolina, United States (Recruiting)
• Investigational Site Number : 0320002 — Buenos Aires, Argentina (Recruiting)
• Hospital de Clinicas de Porto Alegre- Site Number : 0760001 — Porto Alegre, Rio Grande Do Sul, Brazil (Recruiting)
• Investigational Site Number : 3760001 — Ramat Gan, Israel (Recruiting)
• Investigational Site Number : 7920001 — Ankara, Turkey (Recruiting)

Study contacts

• Study coordinator: Trial Transparency email recommended (Toll free for US & Canada)

Conditions Phenylketonuria