A Phase 1/2 interventional study of Tenofovir (TDF) and Emtricitabine (FTC) and Placebo in Aicardi Goutières Syndrome, sponsored by Children's Hospital of Philadelphia. Withdrawn. Open to participants aged 2 Years to 18 Years. Per ClinicalTrials.gov, last updated 2025-05-01.
Sponsored by Children's Hospital of Philadelphia · Phase 1/2, Interventional, and Treatment
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.
The investigators propose that a trial to assess the proof of principle that antiretroviral therapy through a drug combination of Tenofovir (TDF) and Emtricitabine (FTC) can decrease endogenous retroelement accumulation, and alter interferon signaling in Aicardi Goutières Syndrome (AGS) patients is reasonable and warranted at this time, based on existing in vitro and animal data. Additionally, this trial will further the investigators understanding of this disorder, measuring for the first time retroelements in human participants, exploring the retroviral burden in cerebrospinal fluid (CSF), the Interferon (IFN) signaling response, as well as evaluating antigen targets of autoimmunity and cytokines. If successful, this approach will clearly demonstrate the need for a larger trial of antiretrovirals in AGS with more clinically relevant outcomes.
Exclusion Criteria:
This is a double-blind, placebo-controlled, 2 arm, cross-over trial involving 34 children with clinical findings and molecular confirmation of Aicardi Goutieres Syndrome, who also have an abnormal interferon signature. For arm 1, half of the patients will receive TDF/FTC (a combination of Tenofovir \[TDF\] and Emtricitabine \[FTC\]) for the first 6 months of the study. There will be a one month washout period before starting on placebo for 6 months.
Drug: Tenofovir (TDF) and Emtricitabine (FTC) · Other: Placebo
For arm 2, half of the patients will receive placebo for the first 6 months of the study. There will be a one month washout period before starting on TDF/FTC (a combination of Tenofovir \[TDF\] and Emtricitabine \[FTC\]) for 6 months.
Drug: Tenofovir (TDF) and Emtricitabine (FTC) · Other: Placebo
Tenofovir (TDF): a nucleotide reverse transcriptase inhibitor (NtRTI) an acyclic nucleotide analog of adenosine 5'-monophosphate. This is used in children as young as age 2. Emtricitabine (FTC): a nucleoside reverse transcriptase inhibitor (NRTI), a synthetic analog of cytidine which binds at the active site of the reverse transcriptase.
Also known as: Truvada (Tenofovir Disoproxil Fumarate and Emtricitabine), Viread (Brand for tenofovir disoproxil fumarate), Emtriva (Brand for emtricitabine)
Placebo for Tenofovir and Placebo for Emtricitabine
Change in interferon activation as measured by interferon response genes
The investigators propose to measure genes in the IFN stimulatory pathway in AGS patients, as a measure of disease activity and as a possible biomarker of therapeutic activity. Current data suggests that IFN related genes remain elevated in the late teens in AGS affected subjects, making it a more reliable measure of disease activity than IFN alpha. Validation of this preliminary data includes serial measurements in blood across several time points, to assess for variability.
Time frame: From Baseline to 13 months
Determination of immune cell composition in CSF
The investigators will pursue immunophenotyping of CSF cells in AGS subjects. Immunophenotyping and target antigens will further understanding of end organ damage in AGS. Additionally, this may provide biomarkers for therapeutic outcome and disease activity.
Time frame: From Baseline to 13 months
Determination of immune cell composition in blood
The investigators will pursue immunophenotyping of peripheral blood monocytes in AGS participants. Immunophenotyping and target antigens will further our understanding of end organ damage in AGS. Additionally, this may provide biomarkers for therapeutic outcome and disease activity.
Time frame: From Baseline to 13 months
Accumulation of endogenous retroelements as measured in circulating immune cells
Performed by assays from previously collected samples
Time frame: From Baseline to 13 months
Accumulation of endogenous retroelements as measured in circulating CSF
Performed by assays from previously collected samples
Time frame: From Baseline to 13 months
Change in presence of non-specific and specific autoantibodies in blood
Performed by assays from previously collected samples
Time frame: From Baseline to 13 months
Changes in Adverse Events - Safety monitoring laboratory tests
Patient monitoring for adverse effects
Time frame: From Baseline to 13 months and as clinically warranted
Changes in total days hospitalized for disease-related illnesses.
Assess the effects of the treatment
Time frame: Baseline - 13 months
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Nervous System Malformations
Children's Hospital of Philadelphia