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

Trial Summary

What is the purpose of this trial?

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.

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

Eligibility Criteria

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

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.

Negative testing for HIV

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

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

Treatment Details

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.

Participant Groups

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+