TPN-101 in Aicardi-Goutières Syndrome (AGS)

Phase 2

Active, not recruiting

• Conditions: Aicardi-Goutières Syndrome (AGS)
• Interventions: Drug: TPN-101

• Registration Number: NCT05613868
• Lead Sponsor: 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)

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.

Study Timeline

• Study First Submitted: 2022-11-07
• Study First Submitted QC: 2022-11-10
• Study First Posted: 2022-11-14
• Study Start: 2023-03-15
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-04
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Active, TPN-101	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.

Primary Outcome Measures

Name	Time	Method
Change in innate immune signaling	48 weeks	Assessed by the expression of 30 interferon-stimulated genes (ISG), used to calculate an Interferon (IFN) score in whole blood
Incidence and severity of spontaneously reported treatment-emergent adverse events (TEAEs) of TPN-101	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

Trial Locations

Locations (5)

Laboratory of Neurogenetics and Neuroinflammation Imagine Institute - INSERM U1163; 🇫🇷 Paris, France

Presidio Ospedale dei Bambini [Children's Hospital]; 🇮🇹 Brescia, Italy

SST Fatebenefratelli Sacco; 🇮🇹 Milano, Italy

Royal Hospital for Children and Young People; 🇬🇧 Edinburgh, United Kingdom

Istituto Neurologico Casimiro Mondino; 🇮🇹 Pavia, Italy