A Phase 2 interventional study of Imlifidase and GNT0003 in Crigler-Najjar Syndrome, sponsored by Genethon. Recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-03.
Sponsored by Genethon · Phase 2, Interventional, and Treatment
Clinical trial rationale:
CNS is an ultra-rare (\<1/1 million newborns), autosomal recessive disorder of bilirubin conjugation caused by mutation in the gene coding for uridine 5'-diphosphate glucuronosyltransferase (UGT1A1), that causes the accumulation of neurotoxic unconjugated bilirubin (UCB).
Reduction of UCB is managed with phenobarbital in mild CNS, and daily phototherapy in severe CNS.
There is no authorized curative medical treatment for CNS. Liver transplantation is currently the only curative treatment for severe CNS.
GNT0003 is a genetically modified recombinant (r) viral vector composed of the AAV8 viral capsid carrying the UGT1A1 transgene which aims to correct the dysfunction of the mutated gene by achieving durable expression of a functional copy of the affected gene.
Imlifidase (IgG-degrading enzyme) has demonstrated its efficacy in highly sensitized adult kidney transplant patients.
To give participants with pre-existing anti-AAV8 antibodies access to gene therapy treatments, this trial aims to demonstrate the safety and efficacy of GNT0003 following imlifidase pre-treatment in adult participants with severe CNS requiring daily phototherapy and presenting with pre-existing anti-AAV8 antibodies.
Primary objective: to assess efficacy of a single intravenous administration of GNT0003 following imlifidase pre-treatment in participants with severe CNS requiring phototherapy and pre-existing AAV8 antibodies
Secondary objective: to collect data on safety and tolerability of GNT0003 and imlifidase, efficacy of imlifidase, pharmacokinetic and pharmacodynamic profile of GNT0003, and Quality of Life.
The trial will include 3 parts:
A follow-up period:
This trial will be conducted in accordance with the International Conference on Harmonization Guideline for Good Clinical Practice and the Declaration of Helsinki. Participants must be consented using the approved Informed Consent Form before any procedures specified in the protocol are performed.
Genethon is the lead sponsor of 15 studies on the registry; 5 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Main Inclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Each participant will be treated with imlifidase
Drug: Imlifidase
Each participant will be treated with GNT0003
Drug: GNT0003
Imlifidase: single administration (dose is confidential), Lyophilized powder for concentrate for solution for infusion
GNT0003: single administration 5E+12 VG/kg, Sterile concentrate for solution for infusion
Proportion of participants with serum total bilirubin ≤ 300 μmol/L, 48 weeks after GNT0003 infusion and without phototherapy from Week 16
Decrease of serum total bilirubin level after interruption of daily phototherapy; change in serum total bilirubin from baseline to week 48.
Time frame: 48 weeks post GNT0003 administration
Incidence of significant clinical and/or laboratoy abnormalities, of all treatment-emergent adverse events, serious adverse events, adverse events of special interrests, adverse drug reactions, malignancies
Incidence and severity for each body system and laboratory parameter will be presented and summarized overall
Time frame: 48 weeks; 60 months
Change in Health-related quality of Life form baseline to week 48 post GNT0003 administration
Scale 36-Item Short From Survey (SF-36 Health Survey); from 0 (negative) to 100 (positive)
Time frame: 48 weks
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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Studies of the drug tested here: Imlifidase
Crigler-Najjar Syndrome
Genethon