Abstract
Aim 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).
Methods Open label, non-placebo-controlled phase II clinical trial (NCT04731103) in patients <16 years with any of five AGS genotypes. Assessment 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.
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 six weeks. A statistically significant reduction of ISG expression was recorded after three 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 six weeks. The effect of ABC+3TC+AZT at three 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 six weeks. Time to local R&D approval, and to Sponsor authorisation following R&D approval, severely limited patient recruitment.
Methods Open label, non-placebo-controlled phase II clinical trial (NCT04731103) in patients <16 years with any of five AGS genotypes. Assessment 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.
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 six weeks. A statistically significant reduction of ISG expression was recorded after three 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 six weeks. The effect of ABC+3TC+AZT at three 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 six weeks. Time to local R&D approval, and to Sponsor authorisation following R&D approval, severely limited patient recruitment.
| Original language | English |
|---|---|
| Journal | Developmental Medicine & Child Neurology (DMCN) |
| DOIs | |
| Publication status | Published - 4 Dec 2024 |