Aicardi Goutières SyndromePhase 1/2RTI in AGSNCT03304717
Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome
A Phase 1/2 study testing Tenofovir (TDF) and Emtricitabine (FTC) in people with Aicardi Goutières Syndrome, run by Children's Hospital of Philadelphia.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Aicardi Goutières Syndrome
- What is being tested?
- Tenofovir (TDF) and Emtricitabine (FTC)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2025to Dec 2029
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
About this study
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.
Read the detailed description
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.
- Conditions
- Aicardi Goutières Syndrome
- Being tested
- Tenofovir (TDF) and Emtricitabine (FTC), Placebo
- Keywords
- Leukodystrophy, Antiretroviral Drugs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir (TDF) and Emtricitabine (FTC)Drug
Also called Truvada (Tenofovir Disoproxil Fumarate and Emtricitabine), Viread (Brand for tenofovir disoproxil fumarate), Emtriva (Brand for emtricitabine)
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.
PlaceboOther
Placebo for Tenofovir and Placebo for Emtricitabine
| Study group | Role | What they receive |
|---|---|---|
| TDF/FTC then Placebo | Experimental | 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. Receives: Drug: Tenofovir (TDF) and Emtricitabine (FTC); Other: Placebo |
| Placebo then TDF/FTC | Experimental | 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. Receives: Drug: Tenofovir (TDF) and Emtricitabine (FTC); Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Baseline to 13 months
Secondary outcomes (7)
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.
Measured: 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.
Measured: From Baseline to 13 months
Accumulation of endogenous retroelements as measured in circulating immune cells
Performed by assays from previously collected samples
Measured: From Baseline to 13 months
Accumulation of endogenous retroelements as measured in circulating CSF
Performed by assays from previously collected samples
Measured: From Baseline to 13 months
Change in presence of non-specific and specific autoantibodies in blood
Performed by assays from previously collected samples
Measured: From Baseline to 13 months
Changes in Adverse Events - Safety monitoring laboratory tests
Patient monitoring for adverse effects
Measured: From Baseline to 13 months and as clinically warranted
Changes in total days hospitalized for disease-related illnesses.
Assess the effects of the treatment
Measured: Baseline - 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2017
- Study startDec 2025 (estimated)
- Primary completionDec 2029 (estimated)
- Study completionDec 2029 (estimated)
Why it stopped: Results from other clinical trials on AGS established baricitinib as standard of care treatment. Thanks to the knowledge gained in the clinical treatment of AGS, a clinical trial around the effects of RTI in AGS is no longer relevant at this time.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aicardi Goutières SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Human Genome Research Institute (NHGRI), Gilead Sciences, Emerson Resources, National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Adeline Vanderver, MD, Principal investigator, Children's Hospital of PhiladelphiaWilliam Gahl, MD. PhD, Principal investigator, National Institute of Health Genome Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03304717
- Sponsor's protocol ID
- 17-013715
- Other IDs
- U01HD082806-03
- Acronym
- RTI in AGS
- Status last verified
- Apr 2025
- First submitted
- 4 Aug 2017
- Last updated
- 1 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome
- ClinicalTrials.gov ID
- NCT03304717
- Acronym / sponsor ID
- RTI in AGS / 17-013715
- Conditions
- Aicardi Goutières Syndrome
- Keywords
- Leukodystrophy, Antiretroviral Drugs
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Results from other clinical trials on AGS established baricitinib as standard of care treatment. Thanks to the knowledge gained in the clinical treatment of AGS, a clinical trial around the effects of RTI in AGS is no longer relevant at this time.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Human Genome Research Institute (NHGRI), Gilead Sciences, Emerson Resources, National Institutes of Health (NIH)
- Study start
- Dec 2025 (estimated)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 9 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TDF/FTC then Placebo | Experimental | Drug: Tenofovir (TDF) and Emtricitabine (FTC), Other: PlaceboThis 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. |
| Placebo then TDF/FTC | Experimental | Drug: Tenofovir (TDF) and Emtricitabine (FTC), Other: PlaceboFor 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. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir (TDF) and Emtricitabine (FTC)Also: Truvada (Tenofovir Disoproxil Fumarate and Emtricitabine), Viread (Brand for tenofovir disoproxil fumarate), Emtriva (Brand for emtricitabine)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. | Drug | Placebo then TDF/FTC, TDF/FTC then Placebo |
| PlaceboPlacebo for Tenofovir and Placebo for Emtricitabine | Other | Placebo then TDF/FTC, TDF/FTC then Placebo |
Primary outcome
Change in interferon activation as measured by interferon response genes
Time frame: From Baseline to 13 months
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.
7 secondary outcomes
Determination of immune cell composition in CSF
Time frame: From Baseline to 13 months
Determination of immune cell composition in blood
Time frame: From Baseline to 13 months
Accumulation of endogenous retroelements as measured in circulating immune cells
Time frame: From Baseline to 13 months
Accumulation of endogenous retroelements as measured in circulating CSF
Time frame: From Baseline to 13 months
Change in presence of non-specific and specific autoantibodies in blood
Time frame: From Baseline to 13 months
Changes in Adverse Events - Safety monitoring laboratory tests
Time frame: From Baseline to 13 months and as clinically warranted
Changes in total days hospitalized for disease-related illnesses.
Time frame: Baseline - 13 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2025.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adeline Vanderver, MD principal investigator
Children's Hospital of Philadelphia
William Gahl, MD. PhD principal investigator
National Institute of Health Genome Research Institute
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tenofovir (TDF) and Emtricitabine (FTC) in people with Aicardi Goutières Syndrome, run by Children's Hospital of Philadelphia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 May 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in interferon activation as measured by interferon response genes (time frame: From Baseline to 13 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2025.