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Study of GNT0003 and imlifidase in adults with Crigler-Najjar syndrome who require daily phototherapy and have pre-existing AAV8 antibodies

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study focuses on treating patients with Crigler-Najjar syndrome, a severe condition that requires daily light therapy (phototherapy) to control high levels of bilirubin in the blood. The main treatment being tested combines two medications: GNT0003, which is a gene therapy given through an intravenous infusion, and imlifidase, which is given before the gene therapy. GNT0003 contains a modified virus that carries a working copy of the UGT1A1 gene, which is defective in people with this condition.

The purpose of this study is to determine if this combination treatment can help reduce bilirubin levels in adults with Crigler-Najjar syndrome who have existing antibodies against the viral carrier. During the study, participants will receive imlifidase followed by a single dose of GNT0003. Other medications that may be used during the study include sirolimus, prednisolone, and methylprednisolone to help manage the body's response to treatment.

The study will monitor participants for 60 months after treatment to check if the therapy is working and safe. Researchers will measure bilirubin levels in the blood and track how long participants can stay off phototherapy. They will also monitor participants' overall health and quality of life throughout the study period.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial treatment with imlifidase

    You will receive imlifidase through an intravenous (IV) infusion. This medication helps prepare your body for the main treatment.

    During the infusion, your vital signs and overall condition will be monitored.

  2. Step 2

    Main treatment administration

    After the preparation phase, you will receive a single dose of GNT0003 through an IV infusion.

    This medicine contains a modified virus (AAV8) that carries a working copy of the UGT1A1 gene to help treat Crigler-Najjar syndrome.

  3. Step 3

    Initial monitoring period (weeks 1-16)

    You will continue using your regular phototherapy during the first 16 weeks after treatment.

    Regular health checks will include blood tests, physical examinations, and monitoring of vital signs.

    Samples of blood, urine, saliva, and stool will be collected to check how the treatment is working.

  4. Step 4

    Phototherapy reduction phase (after week 16)

    If your condition improves, you may be able to stop phototherapy after week 16.

    Your bilirubin levels will be regularly measured to ensure they remain at safe levels (below 300 µmol/L).

  5. Step 5

    Long-term follow-up

    You will be monitored for 48 weeks after receiving GNT0003 to assess the treatment's effectiveness.

    Additional follow-up will continue for up to 60 months to monitor long-term safety.

    Regular health assessments will include physical examinations, laboratory tests, and quality of life questionnaires.

Who can join the trial?

11 criteria

  • Must be at least 18 years old or of legal age to consent in your location
  • Must have severe Crigler-Najjar syndrome requiring at least 6 hours of phototherapy (light therapy) per day
  • Must have confirmed genetic mutation in the UGT1A1 gene through DNA testing
  • Must have detectable antibodies against AAV8 (a specific type of virus used in gene therapy) in your blood
  • Must have acceptable blood test results, including:
    • Normal or near-normal blood cell counts
    • Normal or near-normal blood clotting tests
    • Kidney function tests within acceptable limits
    • Liver function tests within specified limits
    • Must agree to use reliable birth control methods from the screening visit until at least 48 weeks after receiving the treatment
    • Must be able to understand and sign informed consent documents
    • Must be willing to comply with all study requirements and restrictions

Who cannot join the trial?

15 criteria

  • Presence of pre-existing antibodies (proteins that fight against viruses) that could interfere with the treatment
  • Current participation in other clinical trials or within 30 days before this study
  • History of liver transplantation or currently on liver transplant waiting list
  • Significant liver disease other than Crigler-Najjar Syndrome
  • Active infections or major illness that could affect patient safety
  • Pregnancy or breastfeeding
  • Unable to comply with phototherapy requirements during the study
  • History of allergic reactions to similar treatments
  • Significant kidney problems (as measured by blood tests)
  • Use of medications that could interact with the study treatment
  • Mental conditions that could affect ability to follow study procedures
  • Blood disorders that could affect treatment safety
  • Recent major surgery (within 3 months)
  • History of cancer within the past 5 years
  • Alcohol or drug abuse within the past year
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Investigated drugs

  • GNT0003

    is a gene therapy medication delivered through a single intravenous injection. It uses a modified virus (adeno-associated viral vector) to deliver a working copy of the UGT1A1 gene into the body. This therapy aims to help patients with severe Crigler-Najjar syndrome who need daily phototherapy treatments.

  • Imlifidase

    is a medication given before the gene therapy to prepare the body for treatment. It helps reduce antibodies that might interfere with the gene therapy, specifically in patients who have existing antibodies against the viral vector (AAV8) used in the treatment.

What is already known about the treatment

  • GNT0003

    An investigational gene therapy medication administered through a single intravenous injection, designed to treat Crigler-Najjar syndrome. This therapy uses an adeno-associated viral vector (AAV8) to deliver the UGT1A1 gene to help patients produce the enzyme needed to process bilirubin properly. The treatment is currently being studied in phase 2 clinical trials and is specifically intended for adult patients who require daily phototherapy and have pre-existing antibodies against AAV8.

  • Imlifidase

    A pre-treatment enzyme medication administered intravenously before GNT0003 gene therapy to reduce pre-existing antibodies against the AAV8 viral vector. This enzyme works by breaking down antibodies that might interfere with the gene therapy's effectiveness, thereby potentially improving the success rate of the main treatment. It is being evaluated as part of a combination approach in treating severe Crigler-Najjar syndrome patients.

Investigated diseases

Crigler-Najjar Syndrome - A rare genetic disorder that affects the liver's ability to process bilirubin, a yellow substance produced when red blood cells break down. The condition is characterized by high levels of bilirubin in the blood, which can cause yellowing of the skin and eyes (jaundice). People with this syndrome are born with a defect in the gene that produces the enzyme responsible for converting bilirubin into a form that can be removed from the body. The syndrome exists in two forms, with type I being more severe and present from birth. The condition is inherited in an autosomal recessive pattern, meaning both parents must pass on the defective gene for a child to develop the syndrome.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2023-510405-18-00Protocol codeGNT-018-IDESEstimated enrolment3 patientsSponsorGenethon

sourced from the EU Clinical Trials Register and site verification

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