TPN-101 in Aicardi-Goutières Syndrome (AGS)

Sponsor

Transposon Therapeutics, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05613868

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

3.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

open label, single groupopen 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)

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

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 Names: censavudine

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 Names:

censavudine

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Patients must meet all of the following criteria:

Inclusion

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.
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):
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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Laboratory of Neurogenetics and Neuroinflammation Imagine Institute - INSERM U1163	Paris	France	75015
2	Presidio Ospedale dei Bambini [Children's Hospital]	Brescia	Italy	25123
3	SST Fatebenefratelli Sacco	Milano	Italy	20154
4	Istituto Neurologico Casimiro Mondino	Pavia	Italy	27100
5	Royal Hospital for Children and Young People	Edinburgh	United Kingdom	EH9 1LF