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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 26 June 2023
Main ID:  NCT03921554
Date of registration: 03/04/2019
Prospective Registration: Yes
Primary sponsor: Adeline Vanderver, MD
Public title: JAK Inhibitor Treatment in AGS
Scientific title: Janus Kinase Inhibitor (Baricitinib) for Aicardi Goutières Syndrome
Date of first enrolment: June 3, 2019
Target sample size: 55
Recruitment status: Active, not recruiting
URL:  https://clinicaltrials.gov/show/NCT03921554
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
United States
Contacts
Name:     Adeline Vanderver, MD
Address: 
Telephone:
Email:
Affiliation:  Children's Hospital of Philadelphia
Key inclusion & exclusion criteria

Inclusion Criteria:

- 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).

Exclusion Criteria:

- 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.

- The creatinine should be measured using the Isotopic Dilution Mass Spectrometry
(IDMS) technique to monitor the eGFR if available. Other methods are allowed but
are not preferred. Laboratory testing using other methods will not be used to
monitor the eGFR.

- Have any of the following specific Hematologic abnormalities on screening laboratory
tests:

- Hemoglobin <7 mg/dL (70 g/L). In infants <2 mo of age, 8 mg/dL will be used as a
threshold

- Neutropenia [absolute neutrophil count (ANC) <500 cells/µL]

- CD4 <250 cell/µl on lymphocyte subset testing (where Absolute CD4 count=Absolute
cluster of differentiation 3/ cluster of differentiation 4 (CD3/CD4)
count=CD3/CD4 count=CD4 count=Absolute CD3+CD4+ cells)

- Thrombocytopenia (platelets <30,000/µL). Patients who are on anticoagulation or
having a history of life-threatening bleeding should be excluded if platelet
count is <50,000/µL

- Have any of the following infectious risks:

- Evidence of active infection, at the time of entry or during the screening
period, that in the opinion of the investigator, would pose an unacceptable risk
for participating in the study

- Ongoing or incompletely treated severe or systemic infection, excluding
cellulitis/osteomyelitis that is felt to be attributable to AGS

- Have had symptomatic herpes zoster infection within 12 weeks prior to entry or
during the screening period

- Have a history of disseminated/complicated herpes zoster (for example,
multidermatomal involvement, central nervous system involvement or systemic
involvement including hepatitis or pneumonitis)

- Have a history of active hepatitis B, hepatitis C, or human immunodeficiency
virus (HIV)

- Have had household contact with a person with active tuberculosis (TB) and did
not receive appropriate and documented prophylaxis for TB

- Have or have had a history of lymphoproliferative disease; or signs or symptoms
suggestive of possible lym



Age minimum: 1 Month
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Aicardi Goutieres Syndrome
Intervention(s)
Drug: Baricitinib
Primary Outcome(s)
Measurement of change with AGS scale at baseline [Time Frame: 52 weeks]
Secondary Outcome(s)
Measurement of interferon signaling scores [Time Frame: 52 weeks]
Monitoring of clinically significant serum chemistry laboratory abnormalities [Time Frame: 52 weeks]
Functional measures of neurologic disability [Time Frame: 52 weeks]
Monitoring of clinically significant hematology laboratory abnormalities [Time Frame: 52 weeks]
Gross Motor Function Measure-88 (GMFM-88) [Time Frame: 52 weeks]
Measurement of disease severity assessed by daily diary disease severity scale [Time Frame: 52 weeks]
Monitoring of clinically significant lipid laboratory abnormalities [Time Frame: 52 weeks]
Monitoring of clinically significant urinalysis laboratory abnormalities [Time Frame: 52 weeks]
Monitoring of other clinically significant laboratory abnormalities [Time Frame: 52 weeks]
Secondary ID(s)
18-015414
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Eli Lilly and Company
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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