Crigler-Najjar Syndrome Type IPhase 1/2NCT06641154
Gene Therapy for Crigler Najjar Syndrome Type I (AlphaCN)
A Phase 1/2 study testing GT-UGT1A1-AAV8-02 in people with Crigler-Najjar Syndrome Type I, run by Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare at 2 sites in Russia.
Trial summary
This is a Phase 1/2, multinational, open-label, study to evaluate the safety and efficacy of an intravenous infusion of GT-UGT1A1-AAV8-02 in patients with Crigler-Najjar type 1 aged ≤10 years and requiring phototherapy. Read more about this study
- Who is it for?
- Ages 3 months to 10 years
- Conditions the study is for
- Crigler-Najjar Syndrome Type I
- What is being tested?
- GT-UGT1A1-AAV8-02
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesRussia
- Study dates
- 6 Nov 2024to 1 Nov 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 3 months to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients with severe Crigler-Najjar syndrome resulting from a molecular confirmation of mutations in the UGT1A1 gene and requiring phototherapy male or female at least 3 months (no more 10 years) at the date of signature of informed consent Patient able to give informed assent and/or consent in writing
Who cannot join
- Patients who underwent liver transplantation Patients with chronic hepatitis B or C Patients infected with Human immunodeficiency virus (HIV) Patients with significant underlying liver disease Patients with significant encephalopathy Participation in any other investigational trial during this trial Patients unable or unwilling to comply with the protocol requirements
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Russia2 sites, 2 recruiting
- Recruiting
Alphaviva LLC
Moscow
Dmitry A. Stukanov, +7(916)161-14-45, alphaviva@mail.ru
- Recruiting
Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare
Moscow
Denis V. Rebrikov, Dr., Professor, +7 (495) 531-44-44
About this study
Official title: A Phase I/II, Open Label, Study to Evaluate Safety and Efficacy of an Intravenous Injection of GT-UGT1A1-AAV8-02 (AAV Vector Expressing the UGT1A1 Transgene) in Patients with Crigler-Najjar Syndrome Type I Requiring Phototherapy
This is a Phase 1/2, multinational, open-label, study to evaluate the safety and efficacy of an intravenous infusion of GT-UGT1A1-AAV8-02 in patients with Crigler-Najjar type 1 aged ≤10 years and requiring phototherapy. Patients will received a single administration of GT-UGT1A1-AAV8-02 and will be followed for safety and efficacy of approximately 60 months (5 years):
- a follow-up of approximately 12 months (48 weeks)
- a long term follow-up of approximately 48 months (4 years), in order to be in line with the latest EMEA Guideline on follow-up of patients administered with gene therapy medicinal products, released on 22 Oct.2009 by the Committee for medicinal products for human use.
Read the detailed description
Inherited enzymopathy of uridine diphosphate glucuronosyltransferase 1A1 (Crigler-Najjar syndrome type I) is an orphan disease, that arises from loss of function UGT1A1 genetic variants. Mutations lead to the enzyme's inability in neutralization of bilirubin conjugates. Clinically this condition is represented by jaundice and severe neurologic disorders, which can lead to death in infancy. Diagnosis of Crigler-Najjar syndrome type I is made through biochemical tests and determination the level of unconjugated bilirubin in blood serum, as well as by molecular genetic methods. There is no specific treatment for the disease, except liver transplantation. In common clinical practice phototherapy and plasmapheresis are applied in order to reduce serum concentration of unconjugated bilirubin and destroy or eliminate it from the body. From the very newborn and further, the lifestyle of young patients is dramatically restricted by the long-lasting exposure to phototherapy.
In Russian Federation there are just a few children annually with such disorder. Under our vision is a girl diagnosed Crigler-Najjar type I, who had either opportunity of liver transplantation and long term immunosuppression or receive a gene therapy within previously promising reports in clinics.
The Crigler-Najar syndrome is a convenient subject of choice for a gene therapy application, because the product of the damaged gene is directly related to a well-studied metabolite in the human body. The norms of bilirubin are known to biochemists, and it is clear how to study it's concentration in plasma. In addition, the level of bilirubin usually correlates well with the levels of liver enzymes, which reflect the condition of the liver and the possible viral load of gene constructs that have liver tropism.
Previously successful applications of gene therapy for this syndrome encouraged us to implement this treatment for the first time on children.
GT-UGT1A1-AAV8-02 (alphaglucuronosyltransferasegene unoparvovec, alphacrigen, OGP-001, AAV-TBG1A1) is comprised of a recombinant adeno-associated virus type 2/8 (rAAV2/8), carrying the normal human UGT1A1 gene. rAAV2/8 does not contain viral genes, but only viral inverted terminal repeats (ITRs), that are essential for genome rescue, replication, packaging, and vector persistence. Instead of viral genes, the vector carries a genetic engineering construct that ensures expression of the human UGT1A1 gene under the control of liver specific promoter of the human thyroxine-binding globulin (TBG) gene.
- Conditions
- Crigler-Najjar Syndrome Type I
- Being tested
- GT-UGT1A1-AAV8-02
- Keywords
- Crigler-Najjar syndrome type I, gene therapy, GT-UGT1A1-AAV8-02, Adeno Associated Virus, Crigler-Najjar
- 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.
GT-UGT1A1-AAV8-02Drug
Also called alphaglucuronosyltransferasegene unoparvovec, alphacrigen, OGP-001, AAV-TBG1A1
Intravenous infusion, single dose
| Study group | Role | What they receive |
|---|---|---|
| GT-UGT1A1-AAV8-02 | Experimental | 2 doses of the IMP assessed in the dose escalation, open-label, phase 1/2 study Receives: Drug: GT-UGT1A1-AAV8-02 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients having received the selected dose of GT-UGT1A1-AAV8-02 with serum bilirubin ≤ 300µmol/L within 48 meeks after GT-UGT1A1-AAV8-02 administration and without phototherapy from week 16
Decrease of total Serum bilirubin level after interruption of daily phototherapy (Efficacy); change in serum total biliirubin from baseline to week 48
Measured: 48 weeks
Incidence of Treatment Emergent Adverse Events or Treatement Serious Adverse Events
Incidence of AE/SAE evaluated by changes in laboratory parameters, vital signs, physical examination, reported from baseline to each visit study. Clinically relevant abnormal findings on Laboratory values, Vital Signs, Physical findings will be reported as Adverse Events.
Incidence and Severity of Adverse Events for each body system will be presented for each dose level and summarized overall.
Measured: 48 weeks
Secondary outcomes (1)
Change in Health-related quality of Life for Children from Baseline to Week 48 after GT-UGT1A1-AAV8-02 administration
Quality of Life outcome measure: change of quality of life from Baseline to Week 48 after GT-UGT1A1-AAV8-02 administration.
PedsQL 4.0 Generic Core Scale for pediatrics: 0-100 scale where higher scores indicate better health-related quality of life
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2024
- Study start6 Nov 2024
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crigler-Najjar Syndrome Type IStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06641154
- Sponsor's protocol ID
- GT-UGT1A1-AAV8-02
- Status last verified
- Nov 2024
- First submitted
- 11 Oct 2024
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open Label, Study to Evaluate Safety and Efficacy of an Intravenous Injection of GT-UGT1A1-AAV8-02 (AAV Vector Expressing the UGT1A1 Transgene) in Patients with Crigler-Najjar Syndrome Type I Requiring Phototherapy
- ClinicalTrials.gov ID
- NCT06641154
- Acronym / sponsor ID
- GT-UGT1A1-AAV8-02
- Conditions
- Crigler-Najjar Syndrome Type I
- Keywords
- Crigler-Najjar syndrome type I, gene therapy, GT-UGT1A1-AAV8-02, Adeno Associated Virus, Crigler-Najjar
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of HealthcareOther government
- Study start
- 6 Nov 2024 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2029 (estimated)
- First posted
- 15 Oct 2024 (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, study to evaluate the safety and efficacy of an intravenous infusion of GT-UGT1A1-AAV8-02 in patients with Crigler-Najjar type 1 aged ≤10 years and requiring phototherapy. Patients will received a single administration of GT-UGT1A1-AAV8-02 and will be followed for safety and efficacy of approximately 60 months (5 years):
- a follow-up of approximately 12 months (48 weeks)
- a long term follow-up of approximately 48 months (4 years), in order to be in line with the latest EMEA Guideline on follow-up of patients administered with gene therapy medicinal products, released on 22 Oct.2009 by the Committee for medicinal products for human use.
Detailed description
Inherited enzymopathy of uridine diphosphate glucuronosyltransferase 1A1 (Crigler-Najjar syndrome type I) is an orphan disease, that arises from loss of function UGT1A1 genetic variants. Mutations lead to the enzyme's inability in neutralization of bilirubin conjugates. Clinically this condition is represented by jaundice and severe neurologic disorders, which can lead to death in infancy. Diagnosis of Crigler-Najjar syndrome type I is made through biochemical tests and determination the level of unconjugated bilirubin in blood serum, as well as by molecular genetic methods. There is no specific treatment for the disease, except liver transplantation. In common clinical practice phototherapy and plasmapheresis are applied in order to reduce serum concentration of unconjugated bilirubin and destroy or eliminate it from the body. From the very newborn and further, the lifestyle of young patients is dramatically restricted by the long-lasting exposure to phototherapy.
In Russian Federation there are just a few children annually with such disorder. Under our vision is a girl diagnosed Crigler-Najjar type I, who had either opportunity of liver transplantation and long term immunosuppression or receive a gene therapy within previously promising reports in clinics.
The Crigler-Najar syndrome is a convenient subject of choice for a gene therapy application, because the product of the damaged gene is directly related to a well-studied metabolite in the human body. The norms of bilirubin are known to biochemists, and it is clear how to study it's concentration in plasma. In addition, the level of bilirubin usually correlates well with the levels of liver enzymes, which reflect the condition of the liver and the possible viral load of gene constructs that have liver tropism.
Previously successful applications of gene therapy for this syndrome encouraged us to implement this treatment for the first time on children.
GT-UGT1A1-AAV8-02 (alphaglucuronosyltransferasegene unoparvovec, alphacrigen, OGP-001, AAV-TBG1A1) is comprised of a recombinant adeno-associated virus type 2/8 (rAAV2/8), carrying the normal human UGT1A1 gene. rAAV2/8 does not contain viral genes, but only viral inverted terminal repeats (ITRs), that are essential for genome rescue, replication, packaging, and vector persistence. Instead of viral genes, the vector carries a genetic engineering construct that ensures expression of the human UGT1A1 gene under the control of liver specific promoter of the human thyroxine-binding globulin (TBG) gene.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GT-UGT1A1-AAV8-02 | Experimental | Drug: GT-UGT1A1-AAV8-022 doses of the IMP assessed in the dose escalation, open-label, phase 1/2 study |
Who may qualify
- Ages
- 3 months to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Patients with severe Crigler-Najjar syndrome resulting from a molecular confirmation of mutations in the UGT1A1 gene and requiring phototherapy male or female at least 3 months (no more 10 years) at the date of signature of informed consent Patient able to give informed assent and/or consent in writing
Key exclusion criteria (1 listed)
- Patients who underwent liver transplantation Patients with chronic hepatitis B or C Patients infected with Human immunodeficiency virus (HIV) Patients with significant underlying liver disease Patients with significant encephalopathy Participation in any other investigational trial during this trial Patients unable or unwilling to comply with the protocol requirements
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 |
|---|---|---|
| GT-UGT1A1-AAV8-02Also: alphaglucuronosyltransferasegene unoparvovec, alphacrigen, OGP-001, AAV-TBG1A1Intravenous infusion, single dose | Drug | GT-UGT1A1-AAV8-02 |
Primary outcome
Proportion of patients having received the selected dose of GT-UGT1A1-AAV8-02 with serum bilirubin ≤ 300µmol/L within 48 meeks after GT-UGT1A1-AAV8-02 administration and without phototherapy from week 16
Time frame: 48 weeks
Decrease of total Serum bilirubin level after interruption of daily phototherapy (Efficacy); change in serum total biliirubin from baseline to week 48
Incidence of Treatment Emergent Adverse Events or Treatement Serious Adverse Events
Time frame: 48 weeks
Incidence of AE/SAE evaluated by changes in laboratory parameters, vital signs, physical examination, reported from baseline to each visit study. Clinically relevant abnormal findings on Laboratory values, Vital Signs, Physical findings will be reported as Adverse Events. Incidence and Severity of Adverse Events for each body system will be presented for each dose level and summarized overall.
1 secondary outcome
Change in Health-related quality of Life for Children from Baseline to Week 48 after GT-UGT1A1-AAV8-02 administration
Time frame: 48 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Crigler-Najjar Syndrome Type I
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GT-UGT1A1-AAV8-02 in people with Crigler-Najjar Syndrome Type I, run by Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare at 2 sites in Russia.
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 1 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Russia. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Denis V. Rebrikov, Dr., Professor, (+7 (495) 531-44-44, d_rebrikov@oparina4.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients having received the selected dose of GT-UGT1A1-AAV8-02 with serum bilirubin ≤ 300µmol/L within 48 meeks after GT-UGT1A1-AAV8-02 administration and without phototherapy from week 16 (time frame: 48 weeks). The study lists 2 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 13 Jan 2025.