Gene Therapy for Crigler Najjar Syndrome Type I (AlphaCN)

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-06

Study Completion Date

2029-11-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Gene Therapy for Severe Crigler Najjar Syndrome

NCT03466463

Crigler-Najjar Syndrome

RECRUITING NA

Efficacy and Safety of GNT0003 Following Imlifidase Pre-treatment in Severe Crigler-Najjar Syndrome

NCT06518005

Crigler-Najjar Syndrome

RECRUITING PHASE2

Gene Transfer Clinical Study in Crigler-Najjar Syndrome

NCT03223194

Crigler-Najjar Syndrome

TERMINATED PHASE1

Gene Replacement Therapy for Treatment of Paediatric Patients With CTNNB1 Neurodevelopmental Syndrome

NCT07270549

CTNNB1 Neurodevelopmental Syndrome

RECRUITING PHASE1/PHASE2

Gene Therapy For Children With Variant Late Infantile Neuronal Ceroid Lipofuscinosis 6 (vLINCL6) Disease

NCT02725580

Variant Late-Infantile Neuronal Ceroid Lipofuscinosis

COMPLETED PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Crigler-Najjar Syndrome Type I

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

GT-UGT1A1-AAV8-02

2 doses of the IMP assessed in the dose escalation, open-label, phase 1/2 study

Group Type EXPERIMENTAL

GT-UGT1A1-AAV8-02

Intervention Type DRUG

Intravenous infusion, single dose

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

GT-UGT1A1-AAV8-02

Intravenous infusion, single dose

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

alphaglucuronosyltransferasegene unoparvovec alphacrigen OGP-001 AAV-TBG1A1

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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

Exclusion Criteria

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

Minimum Eligible Age

3 Months

Maximum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No