TPN-101 in Aicardi-Goutières Syndrome (AGS)

NCT05613868 | Terminated Phase 2 DMC

• 1 other identifier: TPN-101-AGS-201
• Study Type: interventional
• Target: 4
• Locations: 3 countries
• Sites: 5

Brief Summary

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

Conditions

Aicardi-Goutières Syndrome (AGS)

Keywords

AGS; TPN-101; censavudine

Outcome Measures

Primary Outcomes (2)

• Change in innate immune signaling

  Assessed by the expression of 30 interferon-stimulated genes (ISG), used to calculate an Interferon (IFN) score in whole blood

  48 weeks

• Incidence and severity of spontaneously reported treatment-emergent adverse events (TEAEs) of TPN-101

  Incidence and severity of spontaneously reported treatment-emergent adverse events (TEAEs) of TPN-101 administered for up to 48 weeks in patients with AGS

  48 weeks

Study Arms (1)

Active, TPN-101

EXPERIMENTAL

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

Interventions

TPN-101 DRUG

100 mg/ day up to 400mg/day of TPN-101

Also known as: censavudine

Active, TPN-101

Eligibility Criteria

• Age: 12 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants of the following ages:
• Cohort 1: Adults (≥ 18 years of age)
• Cohort 2: Adolescents (12 to 17 years of age)
• Cohort 3: Children 5 to 11 years of age
• Cohort 4: Children 1 to \< 5 years of age and \>= 10 kg in weight
• 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
• 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.
• Early onset encephalopathy with psychomotor delay, spasticity, extrapyramidal signs, and microcephaly, the latter appearing in the first year of life
• Calcifications particularly visible at basal ganglia level (putamen, pallidus, and thalamus), but also extending to the periventricular white matter
• Cerebral white matter abnormalities
• Cerebral atrophy
• 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
• 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

You may not qualify if:

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

Sponsors & Collaborators

• Transposon Therapeutics, Inc.: lead

Study Sites (5)

Laboratory of Neurogenetics and Neuroinflammation Imagine Institute - INSERM U1163

Paris, 75015, France

Location

Presidio Ospedale dei Bambini [Children's Hospital]

Brescia, 25123, Italy

Location

SST Fatebenefratelli Sacco

Milan, 20154, Italy

Location

Istituto Neurologico Casimiro Mondino

Pavia, 27100, Italy

Location

Royal Hospital for Children and Young People

Edinburgh, EH9 1LF, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open label study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: open label, single group

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 14, 2022
• Study Start: March 15, 2023
• Primary Completion: February 27, 2025
• Study Completion: February 27, 2025
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); FR (1); GB (1)