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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

Primary Purpose

Phenylketonuria

Status
Recruiting
Phase
Phase 1
Locations
Turkey
Study Type
Interventional
Intervention
SAR444836
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Phenylketonuria

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Adult males, and females of non-child bearing potential, 18-65 years of age at the time of informed consent. Participants who have the diagnosis of PKU due to PAH deficiency One historical plasma Phe value ≥ 600 μmol/L in the preceding 24 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 trial, 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.

Sites / Locations

  • Investigational Site Number: 7920001Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SAR444836

Arm Description

Participants will receive a single dose of SAR444836 on Day 1

Outcomes

Primary Outcome Measures

Incidence of treatment-emergent adverse events (TEAEs)

Secondary Outcome Measures

Proportion of participants with sustained plasma level of Phe<360 μmol/L for ≥4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration
Change from baseline in plasma level of Phe at Week 24 and Week 96 or End of Study following SAR444836 administration
Change from baseline in dietary protein intake at Week 24 and Week 96 or End of Study following SAR444836 administration
Proportion of participants with sustained plasma level of Phe <600 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration
Proportion of participants with sustained plasma level of Phe <120 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration
Change from baseline in plasma Phe: Tyr ratio at Week 24 and Week 96 or End of Study following SAR444836 administration
Number of participants with abnormal laboratory chemistry values
Assessment of the duration of viral vector shedding of SAR444836 in sampling of urine, saliva, and semen at 4-week intervals following SAR444836 administration

Full Information

First Posted
June 23, 2023
Last Updated
August 7, 2023
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT05972629
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 7, 2023 (Actual)
Primary Completion Date
July 2027 (Anticipated)
Study Completion Date
July 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 approximately 102 weeks (approximately 2 years) for each participant and includes a 6-week screening phase and 96-week follow-up period after SAR444836 administration. There will be a total of 41 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 102 weeks due to the administration of SAR444836 to participants in Stage 1A in a serial fashion, or other factors such as delays in scheduling study visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonuria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SAR444836
Arm Type
Experimental
Arm Description
Participants will receive a single dose of SAR444836 on Day 1
Intervention Type
Drug
Intervention Name(s)
SAR444836
Intervention Description
Infusion pump, intravenous infusion (IV)
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events (TEAEs)
Time Frame
From Baseline to Week 96
Secondary Outcome Measure Information:
Title
Proportion of participants with sustained plasma level of Phe<360 μmol/L for ≥4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration
Time Frame
From Baseline to Week 96
Title
Change from baseline in plasma level of Phe at Week 24 and Week 96 or End of Study following SAR444836 administration
Time Frame
From Baseline to Week 96
Title
Change from baseline in dietary protein intake at Week 24 and Week 96 or End of Study following SAR444836 administration
Time Frame
From Baseline to Week 96
Title
Proportion of participants with sustained plasma level of Phe <600 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration
Time Frame
From Baseline to Week 96
Title
Proportion of participants with sustained plasma level of Phe <120 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration
Time Frame
From Baseline to Week 96
Title
Change from baseline in plasma Phe: Tyr ratio at Week 24 and Week 96 or End of Study following SAR444836 administration
Time Frame
From Baseline to Week 96
Title
Number of participants with abnormal laboratory chemistry values
Time Frame
From Baseline to Week 96
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult males, and females of non-child bearing potential, 18-65 years of age at the time of informed consent. Participants who have the diagnosis of PKU due to PAH deficiency One historical plasma Phe value ≥ 600 μmol/L in the preceding 24 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 trial, 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Transparency email recommended (Toll free for US &amp; Canada)
Phone
800-633-1610
Ext
option 6
Email
Contact-US@sanofi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences &amp; Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number: 7920001
City
Ankara
ZIP/Postal Code
06351
Country
Turkey
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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

Learn more about this trial

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

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