Don't get left behind! The modernized is coming. Check it out now.
Say goodbye to!
The new site is coming soon - go to the modernized
Working… Menu
Trial record 1 of 66 for:    ags
Previous Study | Return to List | Next Study

TPN-101 in Aicardi-Goutières Syndrome (AGS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05613868
Recruitment Status : Recruiting
First Posted : November 14, 2022
Last Update Posted : March 31, 2023
Information provided by (Responsible Party):
Transposon Therapeutics, Inc.

Brief Summary:
A phase 2a multi-center, open-label single dose level study of TPN-101 in Patients with Aicardi-Goutières Syndrome (AGS)

Condition or disease Intervention/treatment Phase
Aicardi-Goutières Syndrome (AGS) Drug: TPN-101 Phase 2

Detailed Description:
The study is planned in pediatric and adult patients with AGS that are greater than 1 year and weigh at least 10 kg. The TPN-101 dose will be adjusted from 100 mg to 400 mg based on weight to achieve similar drug exposures in all subjects. The study plans to enroll 10 - 16 subjects. This study includes a 6-8 week Screening Period, a 48-week Open label Treatment Period, and a 12-week Follow-up Period.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: open label, single group
Masking: None (Open Label)
Masking Description: Open label study
Primary Purpose: Treatment
Official Title: A Phase 2a Study of TPN-101 in Patients With Aicardi-Goutières Syndrome (AGS)
Actual Study Start Date : March 15, 2023
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : April 2025

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Active, TPN-101
100 mg/day to 400mg/ study investigational drug TPN-101 once daily for 48 weeks followed by 12 weeks of follow-up period.
Drug: TPN-101
100 mg/ day up to 400mg/day of TPN-101
Other Name: censavudine

Primary Outcome Measures :
  1. Change in innate immune signaling [ Time Frame: 48 weeks ]
    Assessed by the expression of 30 interferon-stimulated genes (ISG), used to calculate an Interferon (IFN) score in whole blood

  2. Incidence and severity of spontaneously reported treatment-emergent adverse events (TEAEs) of TPN-101 [ Time Frame: 48 weeks ]
    Incidence and severity of spontaneously reported treatment-emergent adverse events (TEAEs) of TPN-101 administered for up to 48 weeks in patients with AGS

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   12 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Patients must meet all of the following criteria:


  1. Male or female participants of the following ages:

    1. Cohort 1: Adults (≥ 18 years of age)
    2. Cohort 2: Adolescents (12 to 17 years of age)
    3. Cohort 3: Children 5 to 11 years of age
    4. Cohort 4: Children 1 to < 5 years of age and >= 10 kg in weight
  2. Molecular diagnosis of AGS due to biallelic mutations in 1 of the following 5 genes: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, or SAMHD1, or due to a recognized dominant mutation in TREX1
  3. IFN score in peripheral blood > 2 standard deviations above the mean score of healthy controls measured on 3 occasions, approximately 2 weeks apart, during the 6-week Screening Period.
  4. Clinical syndrome consistent with AGS diagnosis based on clinical, CSF, and radiological findings. The following are examples of such findings (none of these are required for inclusion):

    1. Early onset encephalopathy with psychomotor delay, spasticity, extrapyramidal signs, and microcephaly, the latter appearing in the first year of life
    2. Calcifications particularly visible at basal ganglia level (putamen, pallidus, and thalamus), but also extending to the periventricular white matter
    3. Cerebral white matter abnormalities
    4. Cerebral atrophy
    5. Important systemic symptoms in the early stages of the disease including irritability, feeding and sleeping difficulties, unexplained fevers, and the appearance of chilblain-like skin lesions on the fingers, toes, and ears
  5. Has a reliable caregiver to accompany the patient to all study visits. Caregiver must have frequent contact with patient and be willing to monitor the patient's health and concomitant medications throughout the study

Exclusion Criteria:

  1. Mutation in IFIH1, ADAR1, LSM11, or RNU7-1.
  2. Pre-/perinatal infections, in particular the TORCH complex (toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus)
  3. Presence of other significant neurological disorders; brain tumor or other space-occupying lesion; history of severe head injury
  4. Clinically significant intercurrent illness, medical condition, physical or laboratory abnormality
  5. Autoimmune disease requiring treatment or management (quiescent rheumatoid arthritis, psoriasis, treated autoimmune thyroiditis, or controlled Type 1 diabetes are acceptable)
  6. History of human immunodeficiency virus (HIV), hepatitis B, or any active infection during Screening
  7. History of cancer within 5 years of Screening, with the exception of fully treated non-melanoma skin cancers
  8. Receipt of an experimental agent within 30 days or 5 half-lives prior to Screening, whichever is longer
  9. Prior treatment with an immunomodulator other than a JAK inhibitor within 6 months of Screening; patients taking JAK inhibitors for AGS must have been on a stable dose for one month prior to Screening
  10. Current treatment with a nucleoside reverse transcriptase inhibitor (NRTI) or other antiviral drug
  11. Receipt of systemic corticosteroids within 30 days prior to Screening
  12. Any vaccination within 30 days prior to Screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05613868

Layout table for location contacts
Contact: Jay Soto 301-261-5312

Layout table for location information
Laboratory of Neurogenetics and Neuroinflammation Imagine Institute - INSERM U1163 Recruiting
Paris, France, 75015
Contact: Marie-Louise Frémond         
Principal Investigator: Marie-Louise Frémond         
Presidio Ospedale dei Bambini [Children's Hospital] Not yet recruiting
Brescia, Italy, 25123
Contact: Elisa Maria Fazzi         
Principal Investigator: Elisa Maria Fazzi         
SST Fatebenefratelli Sacco Not yet recruiting
Milano, Italy, 20154
Contact: Davide Tonduti         
Principal Investigator: Davide Tonduti         
Istituto Neurologico Casimiro Mondino Not yet recruiting
Pavia, Italy, 27100
Contact: Simona Orcesi         
Principal Investigator: Simona Orcesi         
United Kingdom
Royal Hospital for Children and Young People Not yet recruiting
Edinburgh, United Kingdom, EH9 1LF
Contact: Jayakara Shetty         
Principal Investigator: Jayakara Shetty         
Sponsors and Collaborators
Transposon Therapeutics, Inc.
Layout table for additonal information
Responsible Party: Transposon Therapeutics, Inc. Identifier: NCT05613868    
Other Study ID Numbers: TPN-101-AGS-201
First Posted: November 14, 2022    Key Record Dates
Last Update Posted: March 31, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Transposon Therapeutics, Inc.:
Additional relevant MeSH terms:
Layout table for MeSH terms
Nervous System Malformations
Autoimmune Diseases of the Nervous System
Pathologic Processes
Nervous System Diseases
Congenital Abnormalities
Autoimmune Diseases
Immune System Diseases