Reverse Transcriptase Inhibitors for Aicardi-Goutières Syndrome

(RTI in AGS Trial)

Overseen By Constance Besnier

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: HIV, Hepatitis B, Renal insufficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 13 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of two medications, Emtricitabine (FTC) and Tenofovir (TDF), for children with Aicardi-Goutières Syndrome (AGS), a rare condition affecting the brain and immune system. The study involves children with confirmed AGS who show signs of immune system activation. Participants will either start with the medication and switch to a placebo (inactive pill) or start with a placebo and switch to the medication. Children diagnosed with AGS and experiencing related symptoms might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires participants to avoid starting new immune-modulating therapies, like corticosteroids, but it doesn't specify if you need to stop other current medications. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Tenofovir (TDF) and Emtricitabine (FTC) are generally well-tolerated. These drugs often treat HIV and have received FDA approval for this purpose. Most people using them for HIV experience no serious side effects, though some may feel nauseous, have diarrhea, or get headaches.

In past studies with similar treatments, side effects were mostly mild to moderate. Although specific data for Aicardi-Goutières Syndrome (AGS) is not yet available, the safety record from other uses suggests these treatments are fairly safe. Since everyone can react differently, discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Aicardi-Goutières Syndrome?

Researchers are excited about using reverse transcriptase inhibitors like Emtricitabine (FTC) and Tenofovir (TDF) for Aicardi-Goutières Syndrome because these drugs target the underlying viral-like activity in the condition. Unlike current treatments, which primarily focus on managing symptoms, these drugs aim to reduce the abnormal interferon signaling that contributes to the disease. By addressing this root cause, FTC and TDF have the potential to modify the disease process itself, offering a new approach that could significantly improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for Aicardi-Goutières Syndrome?

Research suggests that certain medications, such as Tenofovir (TDF) and Emtricitabine (FTC), might help treat Aicardi-Goutières Syndrome (AGS). This trial will evaluate the effects of TDF and FTC, known to block virus growth and potentially reduce harmful immune responses in AGS. Participants in one arm of the trial will receive TDF/FTC for the first 6 months, followed by a placebo, while those in the other arm will start with a placebo and then receive TDF/FTC. Studies have shown these medications work well in other diseases with similar immune problems. Early results indicate possible benefits, but more specific research on AGS remains necessary. ^{1 6 7 8 9}

Who Is on the Research Team?

Adeline Vanderver, MD

Principal Investigator

Children's Hospital of Philadelphia

William Gahl, MD. PhD

Principal Investigator

National Institute of Health Genome Research Institute

Are You a Good Fit for This Trial?

Children aged 2-18 with Aicardi Goutières Syndrome (AGS) can join this trial. They must weigh at least 10 kg, be able to take oral medication or through a tube, and not start new immune therapies during the trial. Participants need negative HIV and Hepatitis B tests, no severe illnesses as judged by the investigator, and must be part of another specific study (MDBP).

Inclusion Criteria

Negative testing for HIV

I am willing to have repeated spinal taps and blood tests for study purposes.

I can take medicine by mouth, NG tube, or G-tube.

Exclusion Criteria

My genetic test shows mutations in ADAR1 or IFIH1.

My liver tests are more than three times the normal limit.

My kidneys are not working well, with a low creatinine clearance rate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TDF/FTC or placebo for 6 months, followed by a 1-month washout period, then crossover to the alternate treatment for another 6 months

13 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Emtricitabine (FTC)
• Placebo
• Tenofovir (TDF)

Trial Overview The trial is testing if Tenofovir (TDF) and Emtricitabine (FTC), which are Reverse Transcriptase Inhibitors, are safe and effective in treating AGS compared to a placebo. Children will receive either the medications or placebo while their health outcomes are monitored.

How Is the Trial Designed?

Group I: TDF/FTC then Placebo Experimental Treatment 2 Interventions

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.

Group II: Placebo then TDF/FTC Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Emerson Resources

Collaborator

Trials

1

Recruited

30+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

National Human Genome Research Institute (NHGRI)

Collaborator

Trials

273

Recruited

299,000+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03304717

NCT03304717 | Reverse Transcriptase Inhibitors in Aicardi ... The overall objectives are to explore the safety and efficacy of Reverse Transcriptase Inhibitors Tenofovir (TDF)/ Emtricitabine (FTC) administered in AGS ...

2. cdek.crib.liu.edu cdek.crib.liu.edu/trial/NCT03304717/

Trial | NCT03304717 This is a double-blind, placebo-controlled, 2 arm, cross-over trial involving 34 children with clinical findings and molecular confirmation of Aicardi Goutieres ...

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.732775/epub

HIV and the IFN Signaling System The Study of Aicardi-Goutières Syndrome Links LINE-1 to Autoimmunity. To answer the above question, we first need to know the nature of ...

4. malacards.org malacards.org/card/aicardi_goutieres_syndrome

Aicardi-Goutieres Syndrome (AGS) Aicardi-Goutieres syndrome is an inherited disorder affecting the brain, immune system, and skin. It leads to severe brain dysfunction, intellectual and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12492902/

Long-term safety and efficacy of emtricitabine and tenofovir ... Overall, declines in bone mineral density occurred in participants who received emtricitabine and tenofovir disoproxil fumarate, which were significantly ...

6. ctv.veeva.com ctv.veeva.com/study/reverse-transcriptase-inhibitors-in-aicardi-goutieres-syndrome

Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome The overall objectives are to explore the safety and efficacy of Reverse Transcriptase Inhibitors Tenofovir (TDF)/ Emtricitabine (FTC) ...

7. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT03304717/

Trial | NCT03304717 This is a double-blind, placebo-controlled, 2 arm, cross-over trial involving 34 children with clinical findings and molecular confirmation of Aicardi Goutieres ...

8. withpower.com withpower.com/trial/phase-2-autoimmune-diseases-of-the-nervous-system-11-2021-21763

Reverse Transcriptase Inhibitors for Aicardi-Goutières ... ... Emtricitabine (FTC) and Tenofovir (TDF) will have tolerable side effects & efficacy for patients with Nervous System Disorders, Autoimmune Neurological ...

9. synapse.patsnap.com synapse.patsnap.com/drug/b792780dd18a4aa5962abcde5bd89f0e

Emtricitabine - Drug Targets, Indications, Patents CONCLUSIONS: There was a significant reduction in eGFR among people with HIV who switched to TLD compared to those switched to DTG + 3TC. Changes in LDL and BMI ...