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

Aicardi Goutieres Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04517253
• Other study ID #: 17571
• Secondary ID: I4V-JE-JAJE
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: October 27, 2020
• Est. completion date: April 30, 2025

Study information

• Verified date: April 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 8
• Est. completion date: April 30, 2025
• Est. primary completion date: October 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months and older

Eligibility

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.

Related Conditions & MeSH terms

• Aicardi Goutieres Syndrome
• Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome
• Fever
• Hyperthermia
• Lipodystrophy
• Nakajo-Nishimura Syndrome
• Skin Diseases
• STING-Associated Vasculopathy With Onset in Infancy
• Syndrome

Intervention

Drug:
• Baricitinib
Administered orally

Locations

Country	Name	City	State
Japan	Tokyo Medical And Dental University Medical Hospital	Bunkyo	Tokyo
Japan	Hiroshima University Hospital	Hiroshima
Japan	Nara Medical University Hospital	Kashihara	Nara
Japan	National Center For Child Health And Development	Setagaya-ku	Tokyo
Japan	Wakayama Medical University Hospital	Wakayama

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Change From Baseline in Mean Daily Diary Scores	Change from Baseline in Mean Daily Diary Scores	Baseline, up to 172 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in Growth Velocity	Change in Growth Velocity	Baseline, up to 172 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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