Clinical Trials for AGS

Drug and therapy development for AGS is evolving quickly. We have multiple clinical trials underway and in planning/development phases across continents. We’ll provide links and some basic information about these trials, and families can always contact info@agsaa.org for more information.

Reverse Transcriptase Inhibitors

With RTIs in AGS we hope to reduce the proliferation of retroelements and the accumulation of genetic "junk," ultimately turning the volume down on AGS alarm signals. Some early studies demonstrate that RTIs do reduce interferon stimulation in AGS, and clinical trials are just starting to ramp up. We don't know yet whether the effect will be enough to have a clinical impact on individuals with AGS, but it's possible this could become part of a combination of medicines. Because RTIs don't directly suppress the immune system, they could be safely combined with drugs that do, like JAK inhibitors.

Read more about Reverse Transcriptase Inhibitors (RTIs) at https://agsaa.org/rtis

Inhibition of Reverse Transcription in Aicardi-Goutières Syndrome (AGS-RTI)

https://clinicaltrials.gov/ct2/show/NCT04731103

• Dates: on-going

• Location: United Kingdom (UK residents only)

• Phase: 2

• Participants: 3 Months to 15 Years   (Child); Patients with mutations in any of TREX1, the three components of the RNase H2 complex (RNASEH2A, RNASEH2B, RNASEH2C: considered as one genotype) or SAMHD1.

This trial available only to residents of the United Kingdom continues upon previous RTI proof of concept work by Yanick Crow:

Rice, Gillian I et al. “Reverse-Transcriptase Inhibitors in the Aicardi–Goutières Syndrome.” The New England journal of medicine vol. 379,23 (2018): 2275-7. doi:10.1056/NEJMc1810983

TPN-101 in Aicardi-Goutières Syndrome (AGS)

https://clinicaltrials.gov/ct2/show/NCT05613868

• Dates: March 15, 2023 - ongoing 

• Location: Italy, France, and the United Kingdom

• Phase: 2

• Participants: 12 Months and older; 1 of the following 5 genes: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, or SAMHD1

This trial will test a new RTI that promises to access and consequently work better in the brain. It's open to everyone in Europe with trial sites in Italy, France, and the United Kingdom. We're actively planning a webinar with the drug manufacturer to describe and explain the trial. We'll notify families and link it here when it's available.

Observational Studies

An observational clinical trial is a scientific study where researchers watch and collect information about people's health without giving them any new treatments. Instead, they observe and record what happens naturally in a group of individuals over time. The goal is to understand how different factors, like lifestyle habits or exposure to certain things, might affect a person's health or the development of a disease. By carefully observing and analyzing this information, scientists can gain valuable insights and make important discoveries that help improve our understanding of diseases and guide future medical treatments.

The Myelin Disorders Biorepository Project (MDBP)

https://clinicaltrials.gov/ct2/show/NCT03047369

• Dates: on-going

• Location: Children’s Hospital of Philadelphia 

• Phase: Observational Study 

• Participants: Male or female of any age; Suspected or confirmed diagnosis of leukodystrophy

The MDBP is an umbrella project for collecting information and samples from patients with multiple leukodystrophies. It serves as the protocol/study under which the AGS Natural History Study has evolved. Patients at the Children’s Hospital of Philadelphia (CHOP) have likely already participated by donating blood samples, medical records, and participating in evaluations.

Past Trials

JAK Inhibition in AGS

• Dates: 2019-2023 (currently winding down)

• Location: Children’s Hospital of Philadelphia 

• Phase: 2

• Participants: ≥1 month of age with clinical diagnosis of AGS

https://www.clinicaltrials.gov/study/NCT03921554
https://www.clinicaltrials.gov/study/NCT01724580

Known to participants as the “JAGA” trials, the original “compassionate use” trial for AGS and related diseases evolved into a Phase 2 trial for many more people with AGS when it was discovered to have a positive effect in Aicardi-Goutieres Syndrome. The dosing and safety protocol of this trial serve as the basis for AGS’ standard (but only) disease modifying therapy.

We consider this clinical trial to be a success and proof of concept that AGS is a treatable disease. Unfortunately, it was begun at a time before AGS had a significant natural history study and/or validated outcome measures for determining the efficacy of the therapy. Additionally, the drug manufacturer originally offered support on compassionate grounds, but never developed an AGS research program nor intended to seek approval from regulatory agencies. As such, families continue to face barriers when trying to access these medications. Please see our page about JAK Inhibition to learn more.

What are Clinical Trials? 

Clinical trials are research studies that test a medical, surgical, or behavioral intervention in those affected by a syndrome like AGS. These trials are the primary way that researchers determine if a new form of treatment or prevention, such as a new drug, diet, or medical device, is safe and effective in people.

What are the phases of a clinical trial? 

We have multiple clinical trials underway and in planning/development phases across continents.

• Phase 1: Researchers test a new drug or treatment in a small group of healthy volunteers and/or people with the disease for the first time and they evaluate its safety, determine a safe dosage range, and identify side effects.

• Phase 2: A drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.

• Phase 3: the drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. More than one Phase III study may be required before a New Drug Application (NDA) may be submitted to the FDA or equivalent in country of trial

• Phase 4: In this phase, studies are done after the drug or treatment has been FDA-approved and marketed to families. The goal is to gather information on the drug’s effect in various populations and identify any side effects associated with long-term use. 

Resource: https://www.fda.gov/patients/drug-development-process/step-3-clinical-research#Clinical_Research_Phase_Studies

Should AGS affected participate? 

Drug and therapy development for AGS is evolving quickly. Without volunteers, clinical trials cannot exist and we would not be able to find new treatments for AGS. Families who participate in clinical trials are on the cutting edge of helping us to find better treatments. Please be sure to check out the brief description, location and links about these trials, and families can always contact info@agsaa.org for more information.