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

A Phase 2/3, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Baricitinib in Adult and Pediatric Japanese Patients With NNS/CANDLE, SAVI, and AGS

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).

Study Overview

• Status: Terminated
• Conditions: Aicardi Goutieres Syndrome; Nakajo-Nishimura Syndrome; Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome; STING-Associated Vasculopathy With Onset in Infancy
• Intervention / Treatment: Drug: Baricitinib

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Wakayama, Japan, 641-0012
    • Wakayama Medical University Hospital
  • Nara
    • Kashihara, Nara, Japan, 634-0813
      • Nara Medical University Hospital
  • Tokyo
    • Bunkyō, Tokyo, Japan, 113-8519
      • Tokyo Medical and Dental University Medical Hospital
    • Setagaya-ku, Tokyo, Japan, 157-8535
      • National Center for Child Health and Development

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have systemic signs and symptoms of inflammation as manifested NNS/CANDLE, SAVI, AGS
• Have been diagnosed with genetic diagnosis
• Men must agree to use a reliable method of birth control during the study
• Women not of child-bearing potential or nonbreastfeeding
• Women must agree to use birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment
• NNS/CANDLE and SAVI patients who are ≥17.5 months of age
• AGS patients who are ≥6 months of age
• Are ≥ 5kg in body weight

Exclusion Criteria:

• Have received immunosuppressive biologic agent/monoclonal antibody/oral JAK inhibitor/OAT3 inhibitor and cannot discontinue prior to investigational product initiation. Note: A washout period is required to each drug.
• Have diagnosis of current active tuberculosis (TB) or, latent TB who did not receive appropriate treatment.
• Have had a serious infection within 12 weeks prior to screening.
• Have a history of lymphoproliferative disease
• Have any history of venous thromboembolic event (VTE) (deep vein thrombosis [DVT]/pulmonary embolism [PE]) prior to screening.
• Have had any major surgery within 8 weeks prior to screening.
• Have previously been enrolled in any other study investigating baricitinib.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CANDLE; Participants with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) were administered an optimized final dosage of baricitinib, ranging from 8 mg to 12 mg daily (initially 8 mg, with gradual escalation to 10 mg and 12 mg), either as tablets or oral suspension, for 12 weeks. This dosage was determined during a prior 8-week dose-adjustment period, tailored to each participant's weight and estimated glomerular filtration rate (eGFR). Participants then continued receiving baricitinib at their optimized dosage for 191.1 weeks.	Drug: Baricitinib; Administered orally; Other Names: LY3009104
Experimental: SAVI; Participants with stimulator of interferon genes (STING)-associated vasculopathy with onset during infancy (SAVI) were administered an optimized final dosage of baricitinib, ranging from 6 mg to 12 mg daily (initially 6 mg, with gradual escalation to 8 mg, 10 mg, and 12 mg), either as tablets or oral suspension, for 24 weeks. This dosage was determined during a prior 8-week dose-adjustment period, tailored to each participant's weight and eGFR. Participants then continued receiving baricitinib at their optimized dosage for 202.9 weeks.	Drug: Baricitinib; Administered orally; Other Names: LY3009104
Experimental: Aicardi-Goutières Syndrome (AGS); Participants with Aicardi-Goutières Syndrome (AGS) were administered an optimized final dosage of baricitinib, ranging from 6 mg to 8 mg daily (initially 6 mg, with gradual escalation to 8 mg), either as tablets or oral suspension, for 24 weeks. This dosage was determined during a prior 8-week dose-adjustment period, tailored to each participant's weight and eGFR. Participants then continued receiving baricitinib at their optimized dosage for 206.1 weeks.	Drug: Baricitinib; Administered orally; Other Names: LY3009104

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment Period)	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.	Baseline, 20 weeks
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment Period)	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.	Baseline, 32 weeks
Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment Period)	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 - 4.25 with the higher score indicating a more severe symptom. Total score was not utilized.	Baseline, 32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment and Maintenance Period)	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.	Baseline, 191.1 weeks
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment and Maintenance Period)	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.	Baseline, 202.9 weeks
Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment and Maintenance Period)	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 - 4.25 with the higher score indicating a more severe symptom. Total score was not utilized.	Baseline, 206.1 weeks
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment Period)	Decrease was defined as total steroid dose at the visit <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline.	CANDLE: Week 20, SAVI and AGS: Week 32
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment and Maintenance Period)	Decrease was defined as total steroid dose <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline.	CANDLE: Week 191.1; SAVI: 202.9 and AGS: Week 206.1
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period)	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.	Baseline, 20 weeks
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period)	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.	Baseline, 32 weeks
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period)	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.	Baseline, 32 weeks
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)	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.	Baseline, 191.1 weeks
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period)	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.	Baseline, 202.9 weeks
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period)	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.	Baseline, 206.1 weeks
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE (Primary Treatment Period)	The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle Visual Analog Scale (VAS) ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity" (Filocamo et al. 2010). Higher scores indicate greater disease severity.	Baseline, 20 weeks
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Primary Treatment Period)	The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle VAS ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity" (Filocamo et al. 2010). Higher scores indicate greater disease severity.	Baseline, 32 weeks
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE (Primary Treatment and Maintenance Period)	The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle Visual Analog Scale (VAS) ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity" (Filocamo et al. 2010). Higher scores indicate greater disease severity.	Baseline, 191.1 weeks
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Maintenance Period)	The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle VAS ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity" (Filocamo et al. 2010). Higher scores indicate greater disease severity.	SAVI: Baseline, 202.9 weeks; AGS: Baseline, 206.1 weeks
Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5 Compared to That in Pre-treatment Period in Participants With CANDLE (Primary Treatment Period)	Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5 Compared to that in Pre-treatment period in Participants with CANDLE was evaluated	Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks
Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5 Compared to That in Pre-treatment Period in Participants With CANDLE (Primary Treatment and Maintenance Period)	Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5 Compared to That in Pre-treatment Period in Participants With CANDLE was evaluated.	Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks
Change From Baseline in Growth Velocity (Height and Weight Z Score) (Primary Treatment and Maintenance Period)	The change from baseline in normalized scores for body weight or height is measured using Z-scores. A Z-score indicates how many standard deviations a person's height or body weight is above or below the average for their age and gender. Z-score which was calculated by (value - [mean of the population]) / [SD of the population] at a given age/sex. Interpretation: Z-score of 0: The measurement is equal to the population mean. Z-score less than 0: The measurement is below the population mean. Z-score greater than 0: The measurement is above the population mean. An increase in the Z-score for weight or height means that the weight or height of the participants has increased more than the standard population during the study. For study participants with Z-scores less than 0 at baseline, an increase in Z-score is considered a positive outcome. A Z-score within the range of -2 to +2 indicates that the height or weight is within the normal range.	CANDLE: Baseline, 191.1 weeks; SAVI: Baseline, 202.9 weeks and AGS: Baseline, 206.1 weeks
Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE (Primary Treatment Period)	Diaries were specific to individual indications or conditions (ie, 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.	Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks
Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)	Diaries were specific to individual indications or conditions (ie, 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.	Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks
Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE (Primary Treatment Period)	The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle Visual Analog Scale (VAS) ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity" (Filocamo et al. 2010). Higher scores indicate greater disease severity.	Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks
Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)	The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle Visual Analog Scale (VAS) ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity" (Filocamo et al. 2010). Higher scores indicate greater disease severity.	Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2020
• Primary Completion (Actual): April 4, 2023
• Study Completion (Actual): November 28, 2024

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: June 22, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: AGS; Nakajo-Nishimura Syndrome; CANDLE; SAVI
• Additional Relevant MeSH Terms: Wounds and Injuries; Pathologic Processes; Metabolic Diseases; Disease; Lipid Metabolism Disorders; Body Temperature Changes; Heat Stress Disorders; Skin Diseases, Metabolic; Hyperthermia; Syndrome; Skin Diseases; Fever; Lipodystrophy
• Other Study ID Numbers: 17571; I4V-JE-JAJE (Other Identifier: Eli Lilly and Company); 2025-000001-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No