Gene Therapy for Crigler Najjar Syndrome Type I (AlphaCN)

NCT06641154 | Recruiting Phase 1 DMC

• 1 other identifier: GT-UGT1A1-AAV8-02
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Crigler-Najjar Syndrome Type I

Keywords

Crigler-Najjar syndrome type I; gene therapy; GT-UGT1A1-AAV8-02; Adeno Associated Virus; Crigler-Najjar

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  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

  48 weeks

Study Arms (1)

GT-UGT1A1-AAV8-02

EXPERIMENTAL

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

Drug: GT-UGT1A1-AAV8-02

Interventions

GT-UGT1A1-AAV8-02 DRUG

Intravenous infusion, single dose

Also known as: alphaglucuronosyltransferasegene unoparvovec, alphacrigen, OGP-001, AAV-TBG1A1

GT-UGT1A1-AAV8-02

Eligibility Criteria

• Age: 3 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare: lead

Study Sites (2)

Alphaviva LLC

Moscow, Russia

RECRUITING

Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare

Moscow, Russia

RECRUITING

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

Central Study Contacts

Denis V. Rebrikov, Dr., Professor,

CONTACT

+7 (495) 531-44-44; d_rebrikov@oparina4.ru

Study Design

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

Study Record Dates

• First Submitted: October 11, 2024
• First Posted: October 15, 2024
• Study Start: November 6, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029
• Last Updated: January 13, 2025

Record last verified: 2024-11

Locations

RU (2)