Developmental medicine and child neurology · 2024
Reverse transcriptase inhibitors in Aicardi-Goutières syndrome: A crossover clinical trial.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод в очереди
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Crow Yanick J, Briggs Tracy A, Eleftheriou Despina, Parida Amitav, Battison Claire, Giddings Annabel, Kennel Titouan, Parker Richard A, AGS‐RTIs Study Group
Аннотация
AIM: To extend the findings of a previous clinical trial suggesting combined abacavir (ABC), lamivudine (3TC), and zidovudine (AZT) reduces type I interferon (IFN) signalling in Aicardi-Goutières syndrome (AGS).
METHOD: This was an open label, non-placebo-controlled phase II clinical trial (NCT04731103) in patients less than 16 years with any of five AGS genotypes. The effect of ABC or 3TC individually, or of combined ABC + 3TC + AZT, on IFN-stimulated gene (ISG) expression (primary outcome) and IFN-alpha protein (secondary outcome) in blood was assessed.
RESULTS: Thirteen patients were recruited. Compliance was poor in the ABC + 3TC + AZT arm. No statistically significant effects were observed with ABC or 3TC, or with ABC + 3TC + AZT over 6 weeks. A statistically significant reduction of ISG expression was recorded after 3 weeks of ABC + 3TC + AZT, which was not mirrored by changes in IFN-alpha protein.
INTERPRETATION: There is insufficient evidence that ABC or 3TC is either effective or ineffective in reducing type I IFN signalling in AGS over 6 weeks. The effect of ABC + 3TC + AZT at 3 weeks supports data from a previous clinical trial of the effect of ABC + 3TC + AZT in reducing type I IFN signalling, although there was insufficient evidence of an effect at 6 weeks. Time to local research and development (R&D) approval, and to sponsor authorization after R&D approval, severely limited patient recruitment.
METHOD: This was an open label, non-placebo-controlled phase II clinical trial (NCT04731103) in patients less than 16 years with any of five AGS genotypes. The effect of ABC or 3TC individually, or of combined ABC + 3TC + AZT, on IFN-stimulated gene (ISG) expression (primary outcome) and IFN-alpha protein (secondary outcome) in blood was assessed.
RESULTS: Thirteen patients were recruited. Compliance was poor in the ABC + 3TC + AZT arm. No statistically significant effects were observed with ABC or 3TC, or with ABC + 3TC + AZT over 6 weeks. A statistically significant reduction of ISG expression was recorded after 3 weeks of ABC + 3TC + AZT, which was not mirrored by changes in IFN-alpha protein.
INTERPRETATION: There is insufficient evidence that ABC or 3TC is either effective or ineffective in reducing type I IFN signalling in AGS over 6 weeks. The effect of ABC + 3TC + AZT at 3 weeks supports data from a previous clinical trial of the effect of ABC + 3TC + AZT in reducing type I IFN signalling, although there was insufficient evidence of an effect at 6 weeks. Time to local research and development (R&D) approval, and to sponsor authorization after R&D approval, severely limited patient recruitment.