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
Overview
- Phase
- Phase 2
- Intervention
- Baricitinib
- Conditions
- Nakajo-Nishimura Syndrome
- Sponsor
- Eli Lilly and Company
- Enrollment
- 10
- Locations
- 5
- Primary Endpoint
- Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment Period)
- Status
- Terminated
- Last Updated
- 9 months ago
Overview
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).
Investigators
Eligibility Criteria
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.
Arms & Interventions
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.
Intervention: Baricitinib
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.
Intervention: Baricitinib
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.
Intervention: Baricitinib
Outcomes
Primary Outcomes
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment Period)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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 Outcomes
- Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment and Maintenance Period)(Baseline, 191.1 weeks)
- Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment and Maintenance Period)(Baseline, 202.9 weeks)
- Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment and Maintenance Period)(Baseline, 206.1 weeks)
- 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)
- 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)
- Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period)(Baseline, 20 weeks)
- Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period)(Baseline, 32 weeks)
- Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period)(Baseline, 32 weeks)
- Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)(Baseline, 191.1 weeks)
- Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period)(Baseline, 202.9 weeks)
- Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period)(Baseline, 206.1 weeks)
- Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE (Primary Treatment Period)(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)(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)(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)(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)(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)(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)(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)(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)(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)(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)(Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks)