JAK Inhibitor Treatment in AGS

NCT03921554 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-015414
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess safety as well as efficacy of baricitinib, a Janus Kinase (JAK) inhibitor, in patients with Aicardi Goutières Syndrome (AGS), a multisystem heritable disorder of the innate immunity resulting in excessive interferon production

Conditions

Aicardi Goutieres Syndrome

Keywords

AGS

Outcome Measures

Primary Outcomes (1)

• Mean and Standard Deviation (SD) of the AGS Scale at 52 Weeks

  The primary objective is to determine if the administration of baricitinib to participants with Aicardi-Goutières Syndrome (AGS) results in a change or stability of the AGS scale from baseline to 52 weeks. The AGS scale is a neurologic scale used to evaluate neurologic function of participants under treatment. The scale includes items for head circumference and developmental milestones. A lower score suggests a worse outcome. The range of scores is from 0 (most severe) to 11 (least severe).

  52 weeks

Secondary Outcomes (4)

• Improvement of the AGS Scale From Screening to Treatment Over Time

  All longitudinal values are included. ASG scores were observed from 578 days (on some patients) before treatment to 2383 days after treatment start (on some patients). At visit 215 (with median treatment days = 673), the mean AGS score was 6.2 (SD = 3.5).

• Improvement of the GMFM-88 Between Screening and Treatment Over Time

  52 weeks

• Change in Interferon Signaling Gene (ISG) Score Between Screening and Treatment Over Time

  All longitudinal values are included. ISG scores were observed from 431 days before treatment to 2383 days after treatment start. At first on treatment visit (median treatment days = 3), the mean ISG score was 14.4 z-score (Standard Deviation = 12.8).

• Measurement of Disease Severity Assessed by Daily Diary Disease Severity Scale

  All longitudinal values are included. Diary scores were observed from 117 days before treatment to 2476 days after treatment start. At visit 210 (median treatment days = 335), the mean diary average score was 1.2 (SD = 0.4).

Study Arms (1)

Aicardi Goutières Syndrome patients receiving Baricitinib

EXPERIMENTAL

Baricitinib will be taken by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib will be dosed by patient age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study will include 1 mg and 2 mg tablets and will be used without splitting. Dispersion will be permitted to aid in swallowing.

Drug: Baricitinib

Interventions

Baricitinib DRUG

Baricitinib will be taken by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib will be dosed by patient age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study will include 1 mg and 2 mg tablets and will be used without splitting. Dispersion will be permitted to aid in swallowing.

Also known as: Olumiant

Aicardi Goutières Syndrome patients receiving Baricitinib

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical or molecular identification of Aicardi Goutières Syndrome including the following features
• Cerebrospinal fluid (CSF) or blood markers suggesting elevations of markers of interferon activation including CSF pleocytosis, elevation of interferon, and/or neopterin and tetrahydrobiopterin elevations
• Evidence of neurologic disease on neuroimaging including intracranial calcifications and or a leukoencephalopathy
• Clinical features of disease including features such as microcephaly, subacute encephalopathy, myopathy, spastic diplegia, skin involvement, autoimmune hepatitis, hematologic abnormalities
• OR have documented mutations felt to be pathogenic in an AGS associated gene.
• Are ≥1 month of age.
• Are ≥4.5 kg in body weight.
• Females after menarche must have a negative urine/serum pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.
• Parental/guardian permission (informed consent).

You may not qualify if:

• Are pregnant or nursing at the time of entry or unable to use contraception as detailed below
• Are females of childbearing potential (women \>12 or who have had at least one menstrual period regardless of age) who are sexually active and who do not agree to use 2 forms of highly effective methods of birth control (see below) or remain abstinent during the study and for at least 28 days following the last dose of investigational product
• Are sexually active males who do not agree to use 2 forms of highly effective birth control (see below) with female partners of childbearing potential or remain abstinent during the study and for at least 28 days following the last dose of investigational product.
• Each of the following is considered a single highly effective method of birth control (the patient should choose 2):
• oral, injectable, or implanted hormonal contraceptives
• condom with spermicidal foam/gel/film/cream/suppository
• occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
• intrauterine device
• intrauterine system (for example, progestin releasing coil)
• vasectomized male (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate)
• Overall health status that in the opinion of the investigator limits the safety of the use of bariticinib
• Have been exposed to a live vaccine within 12 weeks prior to entry or are expected to need/receive a live vaccine (including herpes zoster vaccination) during the course of the study, with the exception of oral rotavirus vaccinations for which the time period is 2 weeks. Young patients who are not yet vaccinated and will be unable to receive live vaccines while they are receiving the program drug (baricitinib) may be included after a documented conversation by a physician not affiliated with the study or the medical monitor with the parents to ensure parental consent and understanding of the risk/benefit ratio of not receiving scheduled vaccinations. These subjects will only be included in the study after a physician obtaining consent also describes the risk/benefit ratio of not receiving scheduled vaccinations.
• Have the following evidence of renal insufficiency:
• An estimated glomerular filtration rate (eGFR) based on the most recent available serum creatinine of \<40 mL/min/1.73 m2 if greater than 2 year of age. eGFR will be calculated using the Bedside Schwartz Equation: eGFR (mL/min/1.73 m2) = (0.413 x height) / SCr, with height measured in cm, and serum creatinine (SCr) in units of mg/dL.
• Children with an eGFR of \<40 mL/min/1.73 m2 will not be enrolled, unless \<24 months of age in which case a cut off of \<30 ml/min/1.73 m2 will be used due to age-based differences in normal eGFR. Normal eGFR of \<60 ml/min/1.73 m2 is common in children \<12 months, and a normal eGFR \<40 ml/min/1.73 m2 is common in infants \<3-6 months.

Sponsors & Collaborators

• Adeline Vanderver, MD: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Adang LA, Gavazzi F, D'Aiello R, Isaacs D, Bronner N, Arici ZS, Flores Z, Jan A, Scher C, Sherbini O, Behrens EM, Goldbach-Mansky R, Olson TS, Lambert MP, Sullivan KE, Teachey DT, Witmer C, Vanderver A, Shults J. Hematologic abnormalities in Aicardi Goutieres Syndrome. Mol Genet Metab. 2022 Aug;136(4):324-329. doi: 10.1016/j.ymgme.2022.06.003. Epub 2022 Jun 16.

  PMID: 35786528 DERIVED

MeSH Terms

Conditions

Aicardi-Goutieres syndrome

Interventions

baricitinib

Limitations and Caveats

Skin manifestations as measured by the CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) is a secondary objective of this study. Completion of the CLASI was not consistently possible during the pandemic; video study visits made this evaluation infeasible. Analysis of the CLASI scores would not be meaningful. Moreover, 4 international subjects did not participate in video visits at 52 weeks, making the AGS severity scale infeasible in those 4 subjects for the primary outcome.

Results Point of Contact

• Title: Dr. Adeline Vanderver
• Organization: Children's Hospital of Philadelphia

vandervera@chop.edu

215-590-1719

Study Officials

• Adeline Vanderver, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Program Director of the Leukodystrophy Center of Excellence of Children's Hospital of Philadelphia, Associate Professor of Neurology

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 19, 2019
• Study Start: June 3, 2019
• Primary Completion: January 4, 2024
• Study Completion: March 25, 2024
• Last Updated: December 30, 2025
• Results First Posted: February 12, 2025

Record last verified: 2025-12

Locations

US (1)