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

Phase 2

Terminated

Conditions: Nakajo-Nishimura Syndrome
Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome
STING-Associated Vasculopathy With Onset in Infancy
Aicardi Goutieres Syndrome

Interventions: Drug: Baricitinib

Registration Number: NCT04517253

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CANDLE	Baricitinib	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.
SAVI	Baricitinib	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.
Aicardi-Goutières Syndrome (AGS)	Baricitinib	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment Period)	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.
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment Period)	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.
Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment Period)	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 - 4.25 with the higher score indicating a more severe symptom. Total score was not utilized.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment and Maintenance Period)	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.
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment and Maintenance Period)	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.
Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment and Maintenance Period)	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 - 4.25 with the higher score indicating a more severe symptom. Total score was not utilized.
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment Period)	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.
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment and Maintenance Period)	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.
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period)	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.
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period)	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.
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period)	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.
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)	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.
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period)	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 (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.
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period)	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) (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.
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE (Primary Treatment Period)	Baseline, 20 weeks	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.
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Primary Treatment Period)	Baseline, 32 weeks	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.
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE (Primary Treatment and Maintenance Period)	Baseline, 191.1 weeks	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.
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Maintenance Period)	SAVI: Baseline, 202.9 weeks; AGS: Baseline, 206.1 weeks	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.
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)	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 was evaluated
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)	Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 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 was evaluated.
Change From Baseline in Growth Velocity (Height and Weight Z Score) (Primary Treatment and Maintenance Period)	CANDLE: Baseline, 191.1 weeks; SAVI: Baseline, 202.9 weeks and AGS: Baseline, 206.1 weeks	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.
Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE (Primary Treatment Period)	Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks	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.
Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)	Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks	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.
Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE (Primary Treatment Period)	Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks	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.
Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)	Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks	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.

Trial Locations

Locations (5): Nara Medical University Hospital
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Kashihara, Nara, Japan
Tokyo Medical And Dental University Medical Hospital
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Bunkyō, Tokyo, Japan
National Center For Child Health And Development
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Setagaya-ku, Tokyo, Japan
Hiroshima University Hospital
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Hiroshima, Japan
Wakayama Medical University Hospital
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Wakayama, Japan
Nara Medical University Hospital
🇯🇵Kashihara, Nara, Japan