Crigler-Najjar SyndromePhase 1VALENSNCT03223194
Gene Transfer Clinical Study in Crigler-Najjar Syndrome
A Phase 1 study testing AT342 in people with Crigler-Najjar Syndrome, run by Audentes Therapeutics at 4 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Crigler-Najjar Syndrome
- What is being tested?
- AT342
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 8 Sep 2017to 11 Feb 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United States2 sites
Clinic for Special Children
Strasburg, Pennsylvania, 17579
Children's Hospital at Montefiore
The Bronx, New York, 10467
United Kingdom1 site
King's College Hospital NHS Foundation Trust
London, SE9 9RS
About this study
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
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.
Read the detailed 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.
- Conditions
- Crigler-Najjar Syndrome
- Being tested
- AT342
- Keywords
- Crigler-Najjar, CN, AAV8 Delivered Gene Transfer, Adeno Associated Virus
- Medical subject headings
- Crigler-Najjar Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT342Genetic
AT342 is an AAV8 vector containing a functional copy of the UGT1A1 gene.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 1.5 x 10^12 vg/kg of AT342 delivered intravenously one time Receives: Genetic: AT342 |
| Cohort 2 | Experimental | 6.0 x 10^12 vg/kg of AT342 delivered intravenously one time Receives: Genetic: AT342 |
| Cohort 3 | Experimental | 1.5 x 10^13 vg/kg of AT342 delivered intravenously one time Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-emergent adverse events (safety and tolerability)
Adverse events, serious adverse events, and laboratory abnormalities (including immunological parameters)
Measured: Baseline to Week 24
Total serum bilirubin
Change in total serum bilirubin
Measured: 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)
Measured: Baseline to Week 18
Secondary outcomes (2)
Phototherapy
Proportion of subjects with successful weaning off of phototherapy
Measured: Baseline to Week 18
UGT Protein
Change in Liver UGT protein expression, DNA, and RNA levels
Measured: 24 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start8 Sep 2017
- Primary completion11 Feb 2021
- Study completion11 Feb 2021
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crigler-Najjar SyndromeStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Audentes Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Suyash Prasad, M.D., Study director, Audentes Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03223194
- Sponsor's protocol ID
- AT342-02
- Acronym
- VALENS
- Status last verified
- May 2022
- First submitted
- 17 Jul 2017
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03223194
- Acronym / sponsor ID
- VALENS / AT342-02
- Conditions
- Crigler-Najjar Syndrome
- Keywords
- Crigler-Najjar, CN, AAV8 Delivered Gene Transfer, Adeno Associated Virus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Audentes TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 8 Sep 2017 (actual)
- Primary completion
- 11 Feb 2021 (actual)
- Study completion
- 11 Feb 2021 (actual)
- First posted
- 21 Jul 2017 (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 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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Genetic: AT3421.5 x 10^12 vg/kg of AT342 delivered intravenously one time |
| Cohort 2 | Experimental | Genetic: AT3426.0 x 10^12 vg/kg of AT342 delivered intravenously one time |
| Cohort 3 | Experimental | Genetic: AT3421.5 x 10^13 vg/kg of AT342 delivered intravenously one time |
| 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. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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 (9 listed)
- 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.
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 |
|---|---|---|
| AT342AT342 is an AAV8 vector containing a functional copy of the UGT1A1 gene. | Genetic | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Treatment-emergent adverse events (safety and tolerability)
Time frame: Baseline to Week 24
Adverse events, serious adverse events, and laboratory abnormalities (including immunological parameters)
Total serum bilirubin
Time frame: Baseline to Week 12 (on phototherapy) and Baseline to Week 18 (off phototherapy)
Change in total serum bilirubin
Hours of Phototherapy
Time frame: Baseline to Week 18
Change in number of hours of daily phototherapy (daily illumination time)
2 secondary outcomes
Phototherapy
Time frame: Baseline to Week 18
UGT Protein
Time frame: 24 Weeks
Results and safety
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2022.
- Individual participant dataSharing planned: No
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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.
Suyash Prasad, M.D. study director
Audentes Therapeutics
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AT342 in people with Crigler-Najjar Syndrome, run by Audentes Therapeutics at 4 sites in 3 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 3 inclusion and 9 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: stopped early, as of the sponsor's last update on 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Israel, United Kingdom. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
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?
Treatment-emergent adverse events (safety and tolerability) (time frame: Baseline to Week 24). The study lists 3 primary outcomes in all. 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 18 May 2022.