Gene Therapy Clinical Trials
Gene therapy to treat Crigler Najjar syndrome. aims to introduce a correct copy of the UGT1A1 gene into the patient's liver cells. This procedure can be accomplished by the administration of specific "vectors" which carry the genetic material to be delivered. Preclinical studies performed on the animal model of the disease (the Gunn rat) provided evidence that gene therapy may promote the correction of the disease.
Several gene therapy clinical trials are being considered as a therapeutic option for the treatment of Crigler-Najjar patients:
Title: A phase I/II, open label, escalating dose study to evaluate safety and efficacy of an intravenous injection of GNT0003 (Adeno-associated Viral Vector expressing the UGT1A1 transgene) in patients with severe Crigler-Najjar syndrome requiring phototherapy.
Abbreviated trial name: CareCN - CureCN
Purpose: To assess safety, tolerability and efficacy of a single intravenous administration of Adeno-associated Viral Vector expressing the UGT1A1 transgene in patients with severe Crigler-Najjar syndrome requiring phototherapy.
Sponsor: Genethon - Developer: Genethon and Spark Therapeutics
Sponsor:This project has received funds from the European 's Union Horizon 2020 research and innovation programme under the grant agreement number 755225 Cure CN Horizon 2020 Project
EU Clinical Trial Register number: 2017-000506-37
EU Clinical Trial Link: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-000506-37/NL
ClinicalTrials.gov Identifier: NCT03466463
ClinicalTrial.gov Link: https://clinicaltrials.gov/ct2/show/NCT03466463?cond=Crigler-Najjar+Syndrome&rank=1
December 2018: The first patient affected by Crigler-Najjar syndrome administered with gene therapy vector in CURE CN trial sponsored by Genethon. A second patient has been treated. No significant side effects were reported, but the reduction of hyperbilirubinemia in both treated patients was transient.
November 2020: A patient affected by Crigler-Najjar syndrome type I underwent gene therapy treatment with an higher dose of viral vector at the Papa Giovanni XXIII Hospital in Bergamo (Italy) by the Prof. Lorenzo D'Antiga's team. March 2021: A second patient has been treated on March 2021, a third on June 2021.
June 2021: Exciting results achieved so far in AAV-mediated gene therapy trial for Crigler Najjar syndrome by Prof. D'Antiga at the Congress of the European Association for the Study of the Liver. In particular, the treatment was well tolerated in the patients treated so far. The administration of the vector at the highest dose resulted in a significant reduction in unconjugated bilirubin levels, allowing the first treated patient to stop phototherapy. The study is still ongoing
Last Update March 2023: Genethon Given PRIME Status by EMA for Gene Therapy To Treat Crigler-Najjar Syndrome
August 2023: Published on New England Journal of Medicine the results of a phase 1-2 study evaluating the safety and efficacy of a single intravenous infusion of an adeno-associated virus serotype 8 vector encoding UGT1A1 in patients with the Crigler-Najjar syndrome that was being treated with phototherapy.
Link to a press release from Genetic Engineering and Biotechnology News
Title: Clinical Assessment Study in Crigler-Najjar Syndrome
Abbreviated trial name: LUSTRO
ClinicalTrials.gov Identifier: NCT03078881
Purpose: Pre-Phase 1 prospective, non-interventional clinical assessment study to evaluate Crigler-Najjar syndrome subjects requiring daily phototherapy, aged 1 year and older.
Sponsor: Audentes Therapeutics (Astallas)
ClinicalTrials.gov Identifier: NCT03078881
ClinicalTrials.gov Link: https://clinicaltrials.gov/ct2/show/NCT03078881
Title: Gene Transfer Clinical Study in Crigler-Najjar Syndrome (VALENS)
Abbreviated trial name: VALENS
Purpose: Phase 1/2, multinational, open-label, ascending-dose, delayed-treatment concurrent control clinical study to evaluate the safety and preliminary efficacy of adeno-associated viral vector expressing the UGT1A1 transgene in subjects with Crigler-Najjar aged ≥1 year.
Sponsor: Audentes Therapeutics
ClinicalTrials.gov Identifier: NCT03223194
ClinicalTrials.gov Link: https://clinicaltrials.gov/ct2/show/NCT03223194
LAST UPDATE: February 2018: First patient affected by Crigler-Najjar syndrome administered with gene therapy vector in VALENS clinical trial sponsored by Audentes. Later the trial was suspended.
