PhenylketonuriaPhase 1/2NCT05972629
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
A Phase 1/2 study testing SAR444836 in people with Phenylketonuria, run by Sanofi at 11 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- SAR444836
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 11 sitesin 5 countries
- Study dates
- 7 Aug 2023to 2 Apr 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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.
Trial locations and contacts
11 sites in 5 countries.
11 sites in 5 countries
United States7 sites
Children's Hospital IMD Clinic- Site Number : 8400015
Aurora, Colorado, 80045
Medical University of SC- Site Number : 8400004
Charleston, South Carolina, 29425
UHCMC- Site Number : 8400014
Cleveland, Ohio, 44106
University of Florida-Genetics- Site Number : 8400010
Gainesville, Florida, 32610
University of Texas- Site Number : 8400002
Houston, Texas, 77030
UPMC Children's Hospital of Pittsburgh-4401 Penn Ave- Site Number : 8400018
Pittsburgh, Pennsylvania, 15224-1334
University of California San Francisco- Site Number : 8400007
San Francisco, California, 94143
Argentina1 site
Investigational Site Number : 0320002
Ciudad Autonoma Buenos Aires, Buenos Aires, 1199
Brazil1 site
Hospital de Clinicas de Porto Alegre - HCPA- Site Number : 0760001
Porto Alegre, Rio Grande do Sul, 90035903
Turkey (Türkiye)1 site
Investigational Site Number : 7920001
Ankara, 06560
About this study
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
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.
Read more
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
- Being tested
- SAR444836
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAR444836Drug
Infusion pump, intravenous infusion (IV)
| Study group | Role | What they receive |
|---|---|---|
| SAR444836 | Experimental | Participants will receive a single dose of SAR444836 on Day 1 Receives: Drug: SAR444836 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events (TEAEs)
Measured: From Baseline to Week 260
Secondary outcomes (8)
Proportion of participants with sustained plasma level of Phe<360 μmol/L for ≥4 weeks without dietary Phe restriction at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Measured: From Baseline to Week 96
Change from baseline in plasma level of Phe at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Measured: From Baseline to Week 96
Change from baseline in dietary protein intake at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Measured: From Baseline to Week 96
Proportion of participants with sustained plasma level of Phe <600 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Measured: From Baseline to Week 96
Proportion of participants with sustained plasma level of Phe <120 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Measured: From Baseline to Week 96
Change from baseline in plasma Phe: Tyr ratio at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Measured: From Baseline to Week 96
Number of participants with abnormal laboratory chemistry values
Measured: From Baseline to Week 96
Assessment of the duration of viral vector shedding of SAR444836 in sampling of urine, saliva, and semen at 4-week intervals following SAR444836 administration
Measured: From Baseline to Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2023
- Study start7 Aug 2023
- Primary completion2 Apr 2030 (estimated)
- Study completion2 Apr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05972629
- Sponsor's protocol ID
- DFI17545
- Other IDs
- U1111-1271-1293, 2022-501200-98
- Status last verified
- Sep 2025
- First submitted
- 23 Jun 2023
- Last updated
- 23 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05972629
- Acronym / sponsor ID
- DFI17545
- Conditions
- Phenylketonuria
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2023 (actual)
- Primary completion
- 2 Apr 2030 (estimated)
- Study completion
- 2 Apr 2030 (estimated)
- First posted
- 2 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SAR444836 | Experimental | Drug: SAR444836Participants will receive a single dose of SAR444836 on Day 1 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAR444836Infusion pump, intravenous infusion (IV) | Drug | SAR444836 |
Primary outcome
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: From Baseline to Week 260
8 secondary outcomes
Proportion of participants with sustained plasma level of Phe<360 μmol/L for ≥4 weeks without dietary Phe restriction at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Change from baseline in plasma level of Phe at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Change from baseline in dietary protein intake at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Proportion of participants with sustained plasma level of Phe <600 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Proportion of participants with sustained plasma level of Phe <120 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Change from baseline in plasma Phe: Tyr ratio at Week 24, 48, and Week 96 or Early Termination Visit following SAR444836 administration
Time frame: From Baseline to Week 96
Number of participants with abnormal laboratory chemistry values
Time frame: From Baseline to Week 96
Assessment of the duration of viral vector shedding of SAR444836 in sampling of urine, saliva, and semen at 4-week intervals following SAR444836 administration
Time frame: From Baseline to Week 96
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2025.
- DFI17545 Plain Language Results SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Related trials for Phenylketonuria
RecruitingPhase 3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
Phenylketonuria
RecruitingPhase 2
A Study of MZE782 in Adults With PKU
Phenylketonuria (PKU)
Recruiting
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
Carrier of Phenylketonuria, Healthy
RecruitingPhase 3
A Study of JNT-517 in Participants With Phenylketonuria (PKU)
Phenylketonuria
Not yet recruiting
Market Research of a Slow Release Protein Substitute for the Dietary Management of PKU
Phenylketonuria (PKU) and Hyperphenylalaninemia, Brain Diseases, Metabolic, Inborn
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
11 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SAR444836 in people with Phenylketonuria, run by Sanofi at 11 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Argentina, Brazil, Israel, Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-emergent adverse events (TEAEs) (time frame: From Baseline to Week 260). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2025.