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
Baricitinib	Baricitinib	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).

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI	Baseline, up to 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	Baseline, up to 32 weeks	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.
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE	Baseline, 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.

Secondary Outcome Measures

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

Trial Locations

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