Crigler Najjar syndrome MedDRA version: 20.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: PT Classification code 10011386 Term: Crigler-Najjar syndrome System Organ Class: 10010331 - Congenit
Conditions
Interventions
Product Name: rAAV8-hUGT1A1
Product Code: AT342
Pharmaceutical Form: Solution for infusion
Sponsors
Audentes Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. 2. Subject is aged =1 year. 3. Subject is prescribed daily phototherapy for a minimum of 6 hours within a 24-hour period (daily illumination time). 4. Signed informed consent by the subject's parent(s) or legally authorized representative(s) (LAR) (if applicable). 5. Subject and parent(s)/LAR(s) are willing and able to comply with study visits and study procedures. 6. Sexually active patients must be willing to use an acceptable method of contraception such as double barrier contraception during the study and for at least 3 months after dose of study treatment. 7. Females of childbearing potential must have a negative pregnancy test within 7 days of dosing and be willing to have additional pregnancy tests during the study. Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject is currently participating in an interventional study or has received gene or cell therapy. 2. 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. 3. Subject has significant cholestatic disease. 4. Subject is receiving phenobarbital or other known inducer of UGT1A1 within 30 days of screening. 5. Subject tests positive for AAV8 antibody with titers >1:20 (subjects under the age of 18 months may be retested in cases where antibodies may have been maternally acquired and titers may decline in the first months of life). 6. 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. 7. Subject has any clinically significant laboratory values, in the opinion of the investigator. 8. Subject has clinically significant underlying liver disease (other than CN). 9. Subject has a history of, or currently has, a clinically important condition other than CN, in the opinion of the investigator. 10. Female subject breastfeeding at screening or planning to become pregnant at any time during study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the safety and preliminary efficacy of AT342 in subjects with Crigler Najjar syndrome requiring daily phototherapy.;Secondary Objective: Not applicable; Primary end point(s): - Change in total serum bilirubin - Change in number of hours of phototherapy over a 24-hour period. ; Timepoint(s) of evaluation of this end point: - Change in total serum bilirubin (Week 12 and 18) - Change in number of hours of phototherapy over a 24-hour period. (Week 18) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of subjects with successful weaning off of phototherapy • A composite endpoint based on change in bilirubin levels and hours of phototherapy • UGT protein expression, DNA, and RNA levels from liver biopsy ; Timepoint(s) of evaluation of this end point: • Proportion of subjects with successful weaning off of phototherapy (at 24 weeks) • A composite endpoint based on change in bilirubin levels and hours of phototherapy (at 18 weeks) • UGT protein expression, DNA, and RNA levels from liver biopsy (at 24 weeks) | — |
Countries
United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Audentes Therapeutics Inc.
Outcome results
None listed