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

Study Overview
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Brief Summary
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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).

Official Title
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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

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

Intervention / Treatment
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* Drug: Baricitinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baricitinib<br>CANDLE: Participants with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) received an optimized dosage of baricitinib that was determined throughout the dose-adjustment period administered as tablets or oral suspension based on participants weight and estimated glomerular filtration rate (eGFR). SAVI: Participants with STING-associated vasculopathy with onset during infancy (SAVI) received an optimized dosage of baricitinib that was determined throughout the dose-adjustment period administered as tablets or oral suspension based on participants weight and estimated glomerular filtration rate (eGFR). Aicardi-Goutières Syndrome (AGS): Participants with Aicardi-Goutières Syndrome (AGS) received an optimized dosage of baricitinib that was determined throughout the dose-adjustment period administered as tablets or oral suspension based on participants weight and estimated glomerular filtration rate (eGFR). | Drug: Baricitinib<br>* Administered orally<br>* Other names: LY3009104;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Daily Diary Scores in Participants With SAVI | 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, up to 32 weeks | 
| Change From Baseline in Mean Daily Diary Scores in Participants With 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, up to 32 weeks | 
| Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE | 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. | Baseline, up to 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Daily Diary Scores | Change from Baseline in Mean Daily Diary Scores | Baseline, up to 172 weeks | 
| Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With SAVI and AGS | Decrease was defined as total steroid dose at the visit <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline. | Week 32 | 
| Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE | Decrease was defined as total steroid dose at the visit <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline. | Week 20 | 
| Number of Participants With Decrease in Daily Dose of Corticosteroids | Number of participants with decrease in Daily Dose of Corticosteroids | Baseline, up to 172 weeks | 
| Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI | 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. | Baseline, up to 32 weeks | 
| Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS | 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. | Baseline, up to 32 weeks | 
| Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE | 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. | Baseline, up to 20 weeks | 
| Change From Baseline in Patient's Symptom Specific Daily Diary Scores | Change from Baseline in Patient's Symptom Specific Daily Diary Scores | Baseline, up to 172 weeks | 
| Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS | 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. | Baseline, up to 32 weeks | 
| Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE | 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. | Baseline, up to 20 weeks | 
| Change From Baseline in the Physician's Global Assessment of Disease Activity Scores | Change From Baseline in the Physician's Global Assessment of Disease Activity Scores | Baseline, up to 172 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 | 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 | 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 | Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5 | Pre-treatment period (average of 12-week pre-treatment data), up to 172 weeks | 
| Change in Growth Velocity | Change in Growth Velocity | Baseline, up to 172 weeks | 
| Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE | 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 | Change from Pre-treatment period in Mean Daily Diary Scores | Pre-treatment period (average of 12-week pre-treatment data), up to 172 weeks | 
| Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE | 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). | 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 | Change from Pre-treatment period in the Physician's Global Assessment of Disease Activity Scores | Pre-treatment period (average of 12-week pre-treatment data), up to 172 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nakajo-Nishimura Syndrome, CANDLE, SAVI, AGS