Gene Transfer Clinical Study in Crigler-Najjar Syndrome

NCT03223194 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: AT342-02
• Study Type: interventional
• Target: 1
• Locations: 3 countries
• Sites: 4

Brief 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.

Conditions

Crigler-Najjar Syndrome

Keywords

Crigler-Najjar; CN; AAV8 Delivered Gene Transfer; Adeno Associated Virus

Outcome Measures

Primary Outcomes (3)

• Treatment-emergent adverse events (safety and tolerability)

  Adverse events, serious adverse events, and laboratory abnormalities (including immunological parameters)

  Baseline to Week 24

• Total serum bilirubin

  Change in total serum bilirubin

  Baseline to Week 12 (on phototherapy) and Baseline to Week 18 (off phototherapy)

• Hours of Phototherapy

  Change in number of hours of daily phototherapy (daily illumination time)

  Baseline to Week 18

Secondary Outcomes (2)

• Phototherapy

  Baseline to Week 18

• UGT Protein

  24 Weeks

Other Outcomes (3)

• Quality of Life Assessment: Pediatric Quality of Life Inventory (PedsQL)

  Baseline to Week 18

• Caregiver Burden Assessment: Family Impact Module Scores

  Baseline to Week 18

• Clinical Global Impression of Severity and of Improvement

  Baseline to Week 18

Study Arms (4)

Cohort 1

EXPERIMENTAL

1.5 x 10\^12 vg/kg of AT342 delivered intravenously one time

Genetic: AT342

Cohort 2

EXPERIMENTAL

6.0 x 10\^12 vg/kg of AT342 delivered intravenously one time

Genetic: AT342

Cohort 3

EXPERIMENTAL

1.5 x 10\^13 vg/kg of AT342 delivered intravenously one time

Genetic: AT342

Delayed-Treatment Control

NO INTERVENTION

Control subjects will generally have the same assessments as treated subjects. Once the optimal dose is selected, control subjects will undergo pre-treatment baseline procedures to confirm that they are eligible to receive treatment with AT342. Once eligible control subjects are dosed with AT342, they will initiate the same post-dose procedures as subjects who received AT342.

Interventions

AT342 GENETIC

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

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Audentes Therapeutics: lead

Study Sites (4)

Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Clinic for Special Children

Strasburg, Pennsylvania, 17579, United States

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

King's College Hospital NHS Foundation Trust

London, SE9 9RS, United Kingdom

Location

MeSH Terms

Conditions

Crigler-Najjar Syndrome

Condition Hierarchy (Ancestors)

Hyperbilirubinemia, Hereditary; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Suyash Prasad, M.D.

  Audentes Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Up to four subjects will be enrolled at each dose level including up to1 subject at each dose level randomized to control with delayed initiation of treatment. One of the dose levels will be chosen for dose expansion and all control subjects will then be treated at the chosen dose level.

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 21, 2017
• Study Start: September 8, 2017
• Primary Completion: February 11, 2021
• Study Completion: February 11, 2021
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); IL (1); GB (1)