Reverse Transcriptase Inhibitors in AGS

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02363452
• Date of registration: 15/01/2015
• Prospective Registration: Yes
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Reverse Transcriptase Inhibitors in AGS RTIs in AGS
• Scientific title: A Pilot Clinical Trial of Reverse Transcriptase Inhibitors in Children With Aicardi-Goutières Syndrome (AGS)
• Date of first enrolment: September 10, 2015
• Target sample size: 11
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02363452
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Yanick CROW, MD, PhD
• Affiliation: Hôpital Necker - Enfants Malades Public Hospitals of Paris

• Name: Stéphane BLANCHE, MD,PhD
• Affiliation: Hôpital Necker - Enfants Malades Public Hospitals of Paris

Key inclusion & exclusion criteria

Inclusion Criteria:

- A molecular diagnosis of AGS i.e. biallelic or known dominant mutations, with
pathogenicity assessed using our extensive mutation database / functional data, in any
of TREX1, RNASEH2A, RNASEH2B, RNASEH2C and SAMHD1 genes

- A pre-defined interferon signature (consistently present, moderate or high, on at
least three occasions, over a period of 6 months prior to enrolment in the study)

- Age = 1 month and < 18 years (either sex)

- Patient beneficiary or affiliated to " health insurance"

- Written informed consent

Exclusion Criteria:

- Pre-existing disease, not due to AGS, which would preclude the use of zidovudine,
Lamivudine and abacavir (as currently assessed in routine clinical HIV-related
practice)

- HLA B57-01 positive result, which indicates a greater risk of abacavir
hypersensitivity reaction

- Patients with abnormally low neutrophile counts (<0.75 x 109/l), or abnormally low
haemoglobin levels (<7.5 g/dl or 4.65 mmol/l)(zidovudine contraindication)

- Positive serology for HIV, HBV

- Known history of cirrhosis and history of clinically relevant hepatitis within last 6
months

- Moderate to severe renal impairment

- Pregnancy, breastfeeding

- Patient participating to a biomedical research with drug



Age minimum: 1 Month
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Aicardi-Goutières Syndrome (AGS)

Intervention(s)

Drug: Reverse transcriptase inhibitors: Zidovudine, Lamivudine, Abacavir

Primary Outcome(s)

Interferon signature [Time Frame: Before and after 12 months of treatment]

Secondary Outcome(s)

Interferon Activity Level in blood (UI/L) [Time Frame: month 18]

Number of chilblains lesions [Time Frame: Month 9]

dosages of abacavir [Time Frame: Month 1]

dosages of abacavir [Time Frame: Month 6]

dosages of zidovudine [Time Frame: Month 1]

dosages of zidovudine [Time Frame: Month 6]

dosages of zidovudine [Time Frame: Month 3]

Interferon Activity Level in cerebrospinal fluid (UI/L) [Time Frame: Within the 12 month on treatment]

Interferon Protein in cerebrospinal fluid (Fg/mL) [Time Frame: within the 12 month on treatment]

Neurological assessment [Time Frame: Month 18]

Number of chilblains lesions [Time Frame: Month 12]

Radiological assessment [Time Frame: Baseline]

Neurological assessment [Time Frame: Month 12]

Radiological assessment [Time Frame: Month 12]

Adverse Events [Time Frame: Baseline until Month 18]

Interferon Activity Level in blood (UI/L) [Time Frame: Within the 12 month on treatment]

dosages of lamivudine [Time Frame: Month 3]

Number of chilblains lesions [Time Frame: Month 3]

dosages of abacavir [Time Frame: Month 3]

dosages of lamivudine [Time Frame: Month 6]

Interferon Protein in blood (Fg/mL) [Time Frame: Month 18]

Interferon Protein in blood (FG/mL) [Time Frame: Within the 12 month on treatment]

Neurological assessment [Time Frame: Baseline]

Interferon signature [Time Frame: Month 18]

dosages of lamivudine [Time Frame: Month 1]

Number of chilblains lesions [Time Frame: baseline]

Number of chilblains lesions [Time Frame: Month 1]

Number of chilblains lesions [Time Frame: Month 18]

Number of chilblains lesions [Time Frame: Month 6]

Secondary ID(s)

P140203

Source(s) of Monetary Support

Please refer to primary and secondary sponsors