ACTIVE_NOT_RECRUITING

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

Conditions

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-08-07
Study Completion:2030-04-02
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05972629

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 65 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Adult males, and females of non-childbearing potential, 18-65 years of age at the time of informed consent.
  2. * Participants must have uncontrolled classical PKU due to PAH deficiency (despite Phe-restricted dietary management or Palynziq) in the judgement of the Investigator.
  3. * 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.
  4. * 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
  5. * Body mass index (BMI) ≤ 35 kg/m2
  6. * Willingness to use effective methods of contraception.
  7. * 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.
  1. * Presence of neutralizing antibodies against the AAV SNY001 capsid
  2. * 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)
  3. * Any significant underlying liver disease or any of the following documented diagnoses, indicative of significant underlying liver disease:
  4. * Portal hypertension; or
  5. * Splenomegaly; or
  6. * Hepatic encephalopathy
  7. * Serum albumin measurement below the lower limit of normal of the laboratory OR AST-to-Platelet Ratio Index \> 1.0
  8. * Serum creatinine \>1.5X ULN
  9. * Hemoglobin A1c \>6.5% or fasting glucose \>126 mg/dL
  10. * Screening laboratory testing demonstrating any of the following:
  11. * HIV; or
  12. * 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
  13. * 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
  14. * Clinically significant, active bacterial, viral, fungal, or parasitic infection (based on Investigator's judgement)

Contacts and Locations

Principal Investigator

Clinical Sciences & Operations
STUDY_DIRECTOR
Sanofi

Study Locations (Sites)

University of California San Francisco - Parnassus Heights- Site Number : 8400007
San Francisco, California, 94143
United States
Children's Hospital Colorado - Aurora- Site Number : 8400015
Aurora, Colorado, 80045
United States
University of Florida College of Medicine- Site Number : 8400010
Gainesville, Florida, 32610
United States
University Hospitals Cleveland Medical Center- Site Number : 8400014
Cleveland, Ohio, 44106
United States
Medical University of South Carolina - Charleston - Jonathan Lucas Street- Site Number : 8400004
Charleston, South Carolina, 29425
United States
The University of Texas Health Science Center- Site Number : 8400002
Houston, Texas, 77401
United States

Collaborators and Investigators

Sponsor: Sanofi

  • Clinical Sciences & Operations, STUDY_DIRECTOR, Sanofi

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-08-07
Study Completion Date2030-04-02

Study Record Updates

Study Start Date2023-08-07
Study Completion Date2030-04-02

Terms related to this study

Additional Relevant MeSH Terms

  • Phenylketonuria