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NCT04517253

A Study of Baricitinib (LY3009104) in Adult and Pediatric Japanese Participants With NNS/CANDLE, SAVI, and AGS

Terminated Phase 2, PHASE3 Results posted Last updated 10 July 2025
What this trial tests

Phase 2, PHASE3 trial testing Baricitinib in Nakajo-Nishimura Syndrome in 10 participants. Terminated before completion.

Timeline
27 October 2020
Primary endpoint
4 April 2023
28 November 2024

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 2, PHASE3
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment10
Start date27 October 2020
Primary completion4 April 2023
Estimated completion28 November 2024
Sites5 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

6 Months and older, any sex, with Nakajo-Nishimura Syndrome or Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment Period) Primary · Baseline, 20 weeks

Diaries were specific to individual indications or conditions (i.e., NNS/CANDLE, SAVI, or AGS). For NNS/CANDLE, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, headache and fatigue in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms \[equivalent to "worst" symptoms\]. The mean daily score range was 0-4 with the higher score indicating a more severe symptom. Total score was not utilized.

GroupValue95% CI
CANDLE-0.217± 0.586
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment Period) Primary · Baseline, 32 weeks

Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For SAVI, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, fatigue, respiratory/breathing problems, and ulcers/ischemic lesions in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms,3 = more severe symptoms, and 4 = severe symptoms \[equivalent to "worst" symptoms\].The mean daily score range was 0-4 with the higher score indicating a more severe symptom. Total score was not utilized.

GroupValue95% CI
SAVI-0.23± 0.238
Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment Period) Primary · Baseline, 32 weeks

Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For AGS, participant or caregiver was instructed to rate each symptom (rating) (neurologic disability (0, 5, 7,10) crying (0, 1, 2, 3), length of uninterrupted sleep (0, 1, 2, 3), generalized seizure (0, 8), fever (0,1), excessive irritability (0, 1, 2, 3), skin findings(body) (0, 1, 2, 3), and skin findings (hands, feet, and ears) (0, 1, 2, 3) with a higher score for each symptom indicating a more severe symptom. The mean daily diary score was the average of all symptom scores and the range was 0 -

GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)-0.045± 0.164
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment and Maintenance Period) Secondary · Baseline, 191.1 weeks

Diaries were specific to individual indications or conditions (i.e., NNS/CANDLE, SAVI, or AGS). For NNS/CANDLE, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, headache and fatigue in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms \[equivalent to "worst" symptoms\]. The mean daily score range was 0-4 with the higher score indicating a more severe symptom. Total score was not utilized.

GroupValue95% CI
CANDLE-0.24± 0.613
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment and Maintenance Period) Secondary · Baseline, 202.9 weeks

Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For SAVI, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, fatigue, respiratory/breathing problems, and ulcers/ischemic lesions in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms,3 = more severe symptoms, and 4 = severe symptoms \[equivalent to "worst" symptoms\].The mean daily score range was 0-4 with the higher score indicating a more severe symptom. Total score was not utilized.

GroupValue95% CI
SAVI-0.286± 0.333
Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment and Maintenance Period) Secondary · Baseline, 206.1 weeks

Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For AGS, participant or caregiver was instructed to rate each symptom (rating) (neurologic disability (0, 5, 7,10) crying (0, 1, 2, 3), length of uninterrupted sleep (0, 1, 2, 3), generalized seizure (0, 8), fever (0,1), excessive irritability (0, 1, 2, 3), skin findings(body) (0, 1, 2, 3), and skin findings (hands, feet, and ears) (0, 1, 2, 3) with a higher score for each symptom indicating a more severe symptom. The mean daily diary score was the average of all symptom scores and the range was 0 -

GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)-0.08± 0.114
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment Period) Secondary · CANDLE: Week 20, SAVI and AGS: Week 32

Decrease was defined as total steroid dose at the visit \<0.15 mg/kg/day (prednisone-equivalent) or \>=50% decrease from baseline.

GroupValue95% CI
CANDLE4
SAVI1
Aicardi-Goutières Syndrome (AGS)1
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment and Maintenance Period) Secondary · CANDLE: Week 191.1; SAVI: 202.9 and AGS: Week 206.1

Decrease was defined as total steroid dose \<0.15 mg/kg/day (prednisone-equivalent) or \>=50% decrease from baseline.

GroupValue95% CI
CANDLE3
SAVI1
Aicardi-Goutières Syndrome (AGS)1
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period) Secondary · Baseline, 20 weeks

Diaries were specific to individual indications or conditions (i.e, NNS/CANDLE,SAVI, or AGS). For NNS/CANDLE, participant or caregiver was instructed to rate each symptom (fatigue, fever, headache, musculoskeletal pain and rash in the diary on a scale from 0 to 4, where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms \[equivalent to "worst" symptoms\]). The mean daily score range was 0-4 with the higher score indicating a more severe symptom.

Fatigue
GroupValue95% CI
CANDLE-0.029± 0.997
Fever
GroupValue95% CI
CANDLE0± 0
Headache
GroupValue95% CI
CANDLE0.057± 0.128
Musculo-skeletal Pain
GroupValue95% CI
CANDLE-0.514± 1.128
Rash
GroupValue95% CI
CANDLE-0.6± 0.894
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period) Secondary · Baseline, 32 weeks

Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For SAVI, participant or caregiver was instructed to rate each symptom (fatigue, fever, musculoskeletal pain, rash, respiratory/breathing problems, and ulcers/ischemic lesions in the diary on a scale from 0 to 4, where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms \[equivalent to "worst" symptoms\]). The mean daily score range was 0-4 with the higher score indicating a more severe symptom.

Fatigue
GroupValue95% CI
SAVI-0.381± 0.541
Fever
GroupValue95% CI
SAVI-0.095± 0.165
Musculo-skeletal Pain
GroupValue95% CI
SAVI-0.238± 0.412
Rash
GroupValue95% CI
SAVI-0.333± 0.577
Respiratory / Breathing Symptoms
GroupValue95% CI
SAVI-0.333± 0.577
Ulcers / Ischemic Lesions
GroupValue95% CI
SAVI0± 0
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period) Secondary · Baseline, 32 weeks

Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For AGS, participant or caregiver was instructed to rate each symptom (rating) (crying (0, 1, 2, 3), excessive irritability (0, 1, 2, 3), fever (0,1), generalized seizure (0, 8), length of uninterrupted sleep (0, 1, 2, 3), neurologic disability (0, 5, 7,10), skin findings(body) (0, 1, 2, 3), and skin findings (hands, feet, and ears) (0, 1, 2, 3) with a higher score for each symptom indicating a more severe symptom.

Crying
GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)0± 0
Excessive Irritability
GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)0± 0
Fever
GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)-0.071± 0.101
Generalized Seizure
GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)0± 0
Length of Uninterrupted Sleep
GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)0.286± 0.404
Neurologic Disability
GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)0± 0
Skin Findings (Body)
GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)-0.5± 0.707
Skin Findings (Hands, Feet, Ears)
GroupValue95% CI
Aicardi-Goutières Syndrome (AGS)-0.071± 0.101
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period) Secondary · Baseline, 191.1 weeks

Diaries were specific to individual indications or conditions (i.e, NNS/CANDLE,SAVI, or AGS). For NNS/CANDLE, participant or caregiver was instructed to rate each symptom (fatigue, fever, headache, musculoskeletal pain and rash in the diary on a scale from 0 to 4, where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms \[equivalent to "worst" symptoms\]). The mean daily score range was 0-4 with the higher score indicating a more severe symptom.

Fatigue
GroupValue95% CI
CANDLE-0.057± 1.172
Fever
GroupValue95% CI
CANDLE0± 0
Headache
GroupValue95% CI
CANDLE0.057± 0.128
Musculo-skeletal Pain
GroupValue95% CI
CANDLE-0.514± 1.128
Rash
GroupValue95% CI
CANDLE-0.686± 0.842

Adverse events — posted to ClinicalTrials.gov

Time frame: CANDLE: Baseline Up to 191.1 Weeks; SAVI: Baseline Up to 202.9 Weeks and AGS: Baseline Up to 206.1 Weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

CANDLE
Serious: 3/5 (60%)
Deaths: 0/5
SAVI
Serious: 1/3 (33%)
Deaths: 1/3
Aicardi-Goutières Syndrome (AGS)
Serious: 0/2 (0%)
Deaths: 0/2

Serious adverse events (8 terms)

ReactionSystemCANDLESAVIAicardi-Goutières Syndrome…
PancytopeniaBlood and lymphatic system disorders
Acute coronary syndromeCardiac disorders
NauseaGastrointestinal disorders
Atypical mycobacterial infectionInfections and infestations
Bronchopulmonary aspergillosisInfections and infestations
PneumoniaInfections and infestations
Haemorrhage intracranialNervous system disorders
HypoaesthesiaNervous system disorders
Other adverse events (81 terms — click to expand)

ReactionSystemCANDLESAVIAicardi-Goutières Syndrome…
Bk polyomavirus test positiveInvestigations
AnaemiaBlood and lymphatic system disorders
Dental cariesGastrointestinal disorders
NauseaGastrointestinal disorders
Covid-19Infections and infestations
GastroenteritisInfections and infestations
NasopharyngitisInfections and infestations
TracheitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Blood creatine phosphokinase increasedInvestigations
DizzinessNervous system disorders
EczemaSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
ThrombocytosisBlood and lymphatic system disorders
BlepharitisEye disorders
Conjunctivitis allergicEye disorders
Abdominal distensionGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
EnterocolitisGastrointestinal disorders
GastritisGastrointestinal disorders
Mouth ulcerationGastrointestinal disorders
StomatitisGastrointestinal disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
XerosisGeneral disorders
Hepatic function abnormalHepatobiliary disorders
Hepatic steatosisHepatobiliary disorders
Adenoviral conjunctivitisInfections and infestations
Bk virus infectionInfections and infestations
ConjunctivitisInfections and infestations
Cytomegalovirus chorioretinitisInfections and infestations
Diarrhoea infectiousInfections and infestations
FolliculitisInfections and infestations
Herpes zosterInfections and infestations
HordeolumInfections and infestations
InfluenzaInfections and infestations
Localised infectionInfections and infestations
Metapneumovirus infectionInfections and infestations

Most-reported serious reactions: Pancytopenia, Acute coronary syndrome, Nausea, Atypical mycobacterial infection, Bronchopulmonary aspergillosis, Pneumonia, Haemorrhage intracranial, Hypoaesthesia.

Data from ClinicalTrials.gov NCT04517253 adverse events section.

Sponsor's own description

The main purpose of this study is to evaluate the efficacy and safety of baricitinib in adult and pediatric Japanese participants with Nakajo-Nishimura Syndrome/chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (NNS/CANDLE), STING-associated vasculopathy with onset during infancy (SAVI), and Aicardi-Goutières Syndrome (AGS).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach.
    Tanaka Y, Luo Y, O'Shea JJ, Nakayamada S. · · 2022 · cited 329× · PMID 34987201 · DOI 10.1038/s41584-021-00726-8
  2. JAK-STAT signaling in human disease: From genetic syndromes to clinical inhibition.
    Luo Y, Alexander M, Gadina M, O'Shea JJ, et al · · 2021 · cited 92× · PMID 34625141 · DOI 10.1016/j.jaci.2021.08.004
  3. Breaking down the cellular responses to type I interferon neurotoxicity in the brain.
    Viengkhou B, Hofer MJ. · · 2023 · cited 37× · PMID 36817430 · DOI 10.3389/fimmu.2023.1110593
  4. The Safety and Efficacy of Tofacitinib in 24 Cases of Pediatric Rheumatic Diseases: Single Centre Experience.
    Kostik MM, Raupov RK, Suspitsin EN, Isupova EA, et al · · 2022 · cited 29× · PMID 35211430 · DOI 10.3389/fped.2022.820586
  5. Current Status of Baricitinib as a Repurposed Therapy for COVID-19.
    Saber-Ayad M, Hammoudeh S, Abu-Gharbieh E, Hamoudi R, et al · · 2021 · cited 24× · PMID 34358107 · DOI 10.3390/ph14070680
  6. FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.
    Lui A, Vanleuven J, Perekopskiy D, Liu D, et al · · 2022 · cited 15× · PMID 36558997 · DOI 10.3390/ph15121546
  7. Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS).
    Kanazawa N, Ishii T, Takita Y, Nishikawa A, et al · · 2023 · cited 13× · PMID 37087470 · DOI 10.1186/s12969-023-00817-8
  8. Emerging Treatments for Childhood Interstitial Lung Disease.
    Bernardinello N, Griese M, Borie R, Spagnolo P. · · 2024 · cited 10× · PMID 37948041 · DOI 10.1007/s40272-023-00603-9

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