Gene Transfer Clinical Study in Crigler-Najjar Syndrome

Crigler-Najjar Syndrome Clinical Trial

— VALENS  

Official title:

VALENS: A Phase 1/2, Randomized, Open-Label, Ascending-Dose, Delayed-Treatment Concurrent Control Clinical Study to Evaluate the Safety and Preliminary Efficacy of AT342, an AAV8-Delivered Gene Transfer Therapy in Crigler-Najjar Syndrome Subjects Aged 1 Year and Older

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03223194
• Other study ID #: AT342-02
• Status: Terminated
• Phase: Phase 1
• Start date: September 8, 2017
• Est. completion date: February 11, 2021

Study information

• Verified date: May 2022
• Source: Audentes Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2, multinational, open-label, ascending-dose, delayed-treatment concurrent control clinical study to evaluate the safety and preliminary efficacy of AT342 in subjects with Crigler-Najjar aged ≥1 year. Subjects will receive a single dose of AT342 and will be followed for safety and efficacy for 5 years.

Description:

This study will evaluate safety and preliminary efficacy of gene transfer in Crigler Najjar Syndrome. Subjects will receive a single dose of AT342 delivered intravenously. A maximum of 3 dose levels of AT342 are planned for evaluation in this study. Up to four subjects will be enrolled at each dose level including up to 1 subject at each dose level randomized to control with delayed administration of the investigational product. Dose escalation to the next dose level will be considered after evaluation of at least 4 weeks of data from subjects dosed at the current dose level. One of the dose levels will be chosen for dose expansion, and the chosen dose will be administered to all delayed-treatment control subjects. The primary efficacy endpoint measure of change in total serum bilirubin will be assessed at weeks 12 (whilst still on phototherapy) and week 18 (after phototherapy has been weaned) after administration of AT342; and the primary efficacy endpoint measure of change in number of hours of phototherapy will be assessed at week 18 This study will utilize an independent Data Monitoring Committee that will monitor subject safety and provide recommendations to Audentes regarding dose escalation, dose expansion, and safety matters. At study termination, only one (1) pediatric participant was enrolled. This study was intended to be a Phase 1/2 trial but the study never moved forward to Phase 2.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: February 11, 2021
• Est. primary completion date: February 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

Key Inclusion Criteria:

• Subject has a diagnosis of Crigler-Najjar syndrome resulting from a confirmed mutation in the UGT1A1 gene as assessed by a Sponsor-approved testing facility.
• Subject is aged =1 year.
• Subject is prescribed daily phototherapy for a minimum of 6 hours within a 24-hour period (daily illumination time).

Key Exclusion Criteria:

• Subject is currently participating in an interventional study or has received gene or cell therapy.
• Subject has received a whole liver, partial liver, or hepatocyte transplant; or subject has a liver transplant scheduled within the treatment period of this study.
• Subject has significant cholestatic disease at screening.
• Subject is receiving phenobarbital or other known inducer of UGT1A1 within 30 days of screening.
• Subject tests positive for AAV8 neutralizing antibodies with titers above protocol specified threshold.
• Other than as required per protocol, subject has received immune-modulating agents within 3 months before dosing (use of inhaled corticosteroids to manage chronic respiratory conditions is allowed); use of other concomitant medications to manage chronic conditions must have been stable for at least 4 weeks before dosing.
• Subject has any clinically significant laboratory values, in the opinion of the investigator.
• Subject has clinically significant underlying liver disease (other than CN) at screening.
• Subject has a history of, or currently has, a clinically important condition other than CN, in the opinion of the investigator.

Related Conditions & MeSH terms

• Cardiomyopathies
• Crigler-Najjar Syndrome
• Syndrome

Intervention

Genetic:
• AT342
AT342 is an AAV8 vector containing a functional copy of the UGT1A1 gene.

Locations

Country	Name	City	State
Israel	Shaare Zedek Medical Center	Jerusalem
United Kingdom	King's College Hospital NHS Foundation Trust	London
United States	Children's Hospital at Montefiore	Bronx	New York
United States	Clinic for Special Children	Strasburg	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Audentes Therapeutics

Countries where clinical trial is conducted

United States,  Israel,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quality of Life Assessment: Pediatric Quality of Life Inventory (PedsQL)	Change in quality of life assessment	Baseline to Week 18
Other	Caregiver Burden Assessment: Family Impact Module Scores	Change in Burden of Disease score	Baseline to Week 18
Other	Clinical Global Impression of Severity and of Improvement	Change in Investigator assessment of disease severity and improvement	Baseline to Week 18
Primary	Treatment-emergent adverse events (safety and tolerability)	Adverse events, serious adverse events, and laboratory abnormalities (including immunological parameters)	Baseline to Week 24
Primary	Total serum bilirubin	Change in total serum bilirubin	Baseline to Week 12 (on phototherapy) and Baseline to Week 18 (off phototherapy)
Primary	Hours of Phototherapy	Change in number of hours of daily phototherapy (daily illumination time)	Baseline to Week 18
Secondary	Phototherapy	Proportion of subjects with successful weaning off of phototherapy	Baseline to Week 18
Secondary	UGT Protein	Change in Liver UGT protein expression, DNA, and RNA levels	24 Weeks