NCT04731103: AGS-RTI

Inhibition of Reverse Transcription in Aicardi-Goutières Syndrome

Completed Phase 2 Last updated 9 May 2024

What this trial tests

Phase 2 trial testing Abacavir (ABC) in Aicardi-Goutières Syndrome in 13 participants. Completed in 11 March 2024.

Timeline

24 August 2022

Primary endpoint
11 March 2024

11 March 2024

Quick facts

Lead sponsor	University of Edinburgh
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	13
Start date	24 August 2022
Primary completion	11 March 2024
Estimated completion	11 March 2024
Sites	1 location across United Kingdom

Drugs / interventions tested

• Abacavir (ABC) — full drug profile →
• Lamivudine (3TC) — full drug profile →
• Abacavir (ABC)+Lamivudine (3TC)+Zidovudine (AZT) — full drug profile →

Conditions studied

• Aicardi-Goutières Syndrome — all drugs for Aicardi-Goutières Syndrome →

Sponsor

University of Edinburgh

Who can join

Adults 3 Months to 15, any sex, with Aicardi-Goutières Syndrome. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Aicardi-Goutières syndrome (AGS) is a disease of children, particularly affecting the brain and the skin. There is a close link between AGS and increased amounts of a chemical called interferon. Normally humans only produce interferon when they are infected with a virus. In AGS, there is no viral infection. Instead, the cells in the cells of affected patients are confused into thinking that their own genetic material is coming from a virus. As a result they produce interferon all the time, which acts as a poison that damages the cells. The Investigators wish to treat AGS patients with drugs called reverse transcriptase inhibitors (RTIs), used to fight the HIV-1 virus that causes AIDS. The investigators will monitor the effect of treatment on interferon levels, and look at other markers which might give us clues to how the drugs are working. The trial is funded by the Medical Research Council, and involves experts based in Edinburgh, Birmingham, Manchester and Great Ormond Street Hospital.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. The type I interferonopathies: 10 years on.
   Crow YJ, Stetson DB. · · 2022 · cited 334× · PMID 34671122 · DOI 10.1038/s41577-021-00633-9
2. The brain microvasculature is a primary mediator of interferon-α neurotoxicity in human cerebral interferonopathies.
   Viengkhou B, Hayashida E, McGlasson S, Emelianova K, et al · · 2024 · cited 21× · PMID 38878770 · DOI 10.1016/j.immuni.2024.05.017
3. Autoinflammatory encephalopathy due to PTPN1 haploinsufficiency: a case series.
   Zhu G, Didry-Barca B, Seabra L, Rice GI, et al · · 2025 · cited 8× · PMID 39986310 · DOI 10.1016/s1474-4422(24)00526-x
4. Reverse transcriptase inhibitors in Aicardi-Goutières syndrome: A crossover clinical trial.
   Crow YJ, Briggs TA, Eleftheriou D, Parida A, et al · · 2025 · cited 5× · PMID 39630935 · DOI 10.1111/dmcn.16199
5. Pharmacological evaluation of drug therapies in Aicardi-Goutières syndrome: insights from patient-derived neural stem cells.
   Braidotti S, Ferraro RM, Franca R, Genova E, et al · · 2025 · PMID 40183101 · DOI 10.3389/fphar.2025.1549183
6. Sterile activation of RNA-sensing pathways in autoimmunity.
   Li J, Zhu J, Yang H, Hou F. · · 2024 · PMID 39143032 · DOI 10.1093/jmcb/mjae029