Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome

• Status: Not yet recruiting
• Trial end date: 2026-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The overall objectives are to explore the safety and efficacy of Reverse Transcriptase Inhibitors Tenofovir (TDF)/ Emtricitabine (FTC) administered in AGS affected children 2 to 18 years of age.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital of Philadelphia
• Collaborators: Emerson Resources; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Gilead Sciences; National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH)
• Treatments: Emtricitabine; Reverse Transcriptase Inhibitors; Tenofovir

Criteria

Inclusion Criteria:

• Molecular, neuroimaging, and clinical findings consistent with a diagnosis of AGS, with the exception of Double-stranded RNA-specific adenosine deaminase (ADAR1) and IFIH1, which are not postulated to result in nucleic acid accumulation

• Evidence of interferon activation such as elevation of CSF neopterin/tetrahydrobiopterin measured on the first evaluation.

• Ages 2-18 years (the age of 2 years is used because the drugs are FDA approved in children greater than 2 years)

• Weight of at least 10 kg

• Willingness to undergo serial lumbar punctures and blow draws for evaluation of laboratory based outcome measures

• Willingness to abstain from initiating the use of immune modulating therapies including corticosteroids

• Able to receive medications orally, by nasogastric (NG) tube or by Gastric (G)-tube

• No concomitant illness which would preclude safe participation as judged by the investigator

• Signed informed consent by the subject's legally acceptable representative

• Negative testing for HIV

• Negative testing for Hepatitis B

• Concurrent enrollment in the Myelin Disorders Biorepository Project (MDBP, ClinicalTrials.gov NCT03047369) and willingness to undergo associated procedures

Exclusion Criteria:

• Age < 2 years or >18 years

• Hepatic insufficiency with liver function tests greater than 3-times the upper limit of normal

• Renal insufficiency with creatinine clearance <60

• Significant malabsorption

• Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at an additional risk by participating in this study

• HIV infection

• Hepatitis B infection

• Mutations in ADAR1 or IFIH1