Aicardi Goutieres Syndrome, Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome, Nakajo-Nishimura Syndrome, STING-Associated Vasculopathy With Onset in Infancy
Conditions
Keywords
Nakajo-Nishimura Syndrome, CANDLE, SAVI, AGS
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).
Interventions
DRUGBaricitinib
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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 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. |
Countries
Japan
Participant flow
Recruitment details
Per analysis plan,only for participants with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE),a pretreatment period lasted for 12 weeks, during which natural history data were collected.This data serves as baseline to assess changes during baricitinib treatment for evaluating key secondary outcomes: Percentage of days with a mean daily symptom score below 0.5,Average daily symptom score,and the Physician's Global Assessment of Disease Activity scores.
Pre-assignment details
Participants who met all eligibility criteria underwent an 8-week dose adjustment period and received an optimized dosage of baricitinib during the primary treatment period (12 weeks \[week 8 to week 20\] for CANDLE and 24 weeks \[week 8 to week 32\] for SAVI or AGS participants), followed by a maintenance period of up to 191.1 weeks for CANDLE participants, and up to 202.9 weeks for SAVI participants, and up to 206.1 weeks for AGS participants.
Participants by arm
| Arm | Count |
|---|---|
| CANDLE Participants with 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 eGFR. Participants then continued receiving baricitinib at their optimized dosage for 191.1 weeks. | 5 |
| SAVI Participants with 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. | 3 |
| Aicardi-Goutières Syndrome (AGS) Participants with 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. | 2 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Maintenance Period | Study Terminated by Sponsor | 3 | 2 | 2 |
| Maintenance Period | Withdrawal by Subject | 1 | 0 | 0 |
| Primary Treatment Period | Adverse Event | 1 | 0 | 0 |
| Primary Treatment Period | Death | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Aicardi-Goutières Syndrome (AGS) | Total | CANDLE | SAVI |
|---|---|---|---|---|
| Age, Continuous | 7.50 years STANDARD_DEVIATION 2.12 | 24.00 years STANDARD_DEVIATION 19.07 | 39.20 years STANDARD_DEVIATION 13.79 | 9.70 years STANDARD_DEVIATION 9.81 |
| Baseline estimated glomerular filtration rate (eGFR) | 99.80 mL/min/1.73m^2 STANDARD_DEVIATION 9.77 | 115.11 mL/min/1.73m^2 STANDARD_DEVIATION 20.08 | 124.69 mL/min/1.73m^2 STANDARD_DEVIATION 19.32 | 109.37 mL/min/1.73m^2 STANDARD_DEVIATION 22.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 10 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mean Daily Diary Score AGS | 0.705 score on a scale STANDARD_DEVIATION 0.77 | 0.705 score on a scale STANDARD_DEVIATION 0.77 | — | — |
| Mean Daily Diary Score CANDLE | — | 0.92 score on a scale STANDARD_DEVIATION 0.345 | 0.92 score on a scale STANDARD_DEVIATION 0.345 | — |
| Mean Daily Diary Score SAVI | — | 0.786 score on a scale STANDARD_DEVIATION 0.275 | — | 0.786 score on a scale STANDARD_DEVIATION 0.275 |
| Pre- Treatment Period:Baseline (Average) Mean Daily Diary Score | — | 0.642 score on a scale STANDARD_DEVIATION 0.322 | 0.642 score on a scale STANDARD_DEVIATION 0.322 | — |
| Pre-Treatment Period: Baseline (Average) % of days where participants' daily diary score was < 0.5. | — | 35.6 Percentage (%) of days STANDARD_DEVIATION 24.4 | 35.6 Percentage (%) of days STANDARD_DEVIATION 24.4 | — |
| Pre-Treatment Period:Baseline (Average) Physician's Global Assessment of Disease Activity Scores | — | 5.45 score on a scale STANDARD_DEVIATION 1.33 | 5.45 score on a scale STANDARD_DEVIATION 1.33 | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 10 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 2 participants | 10 participants | 5 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 4 Participants | 0 Participants |
| Weight >=10 -<20 | 2 Participants | 4 Participants | 0 Participants | 2 Participants |
| Weight >=40 -<50 | 0 Participants | 5 Participants | 4 Participants | 1 Participants |
| Weight >=50 -<60 | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 1 / 3 | 0 / 2 |
| other Total, other adverse events | 5 / 5 | 3 / 3 | 2 / 2 |
| serious Total, serious adverse events | 3 / 5 | 1 / 3 | 0 / 2 |
Outcome results
Primary
Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment Period)
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.
Time frame: Baseline, 32 weeks
Population: AGS: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment Period) | -0.045 score on a scale | Standard Deviation 0.164 |
Primary
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment Period)
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.
Time frame: Baseline, 20 weeks
Population: CANDLE: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment Period) | -0.217 score on a scale | Standard Deviation 0.586 |
Primary
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment Period)
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.
Time frame: Baseline, 32 weeks
Population: SAVI: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment Period) | -0.23 score on a scale | Standard Deviation 0.238 |
Secondary
Change From Baseline in Growth Velocity (Height and Weight Z Score) (Primary Treatment and Maintenance Period)
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.
Time frame: CANDLE: Baseline, 191.1 weeks; SAVI: Baseline, 202.9 weeks and AGS: Baseline, 206.1 weeks
Population: CANDLE, SAVI and AGS: All enrolled participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CANDLE | Change From Baseline in Growth Velocity (Height and Weight Z Score) (Primary Treatment and Maintenance Period) | Height | 3.03 Z-score | — |
| CANDLE | Change From Baseline in Growth Velocity (Height and Weight Z Score) (Primary Treatment and Maintenance Period) | Weight | 0.92 Z-score | — |
| SAVI | Change From Baseline in Growth Velocity (Height and Weight Z Score) (Primary Treatment and Maintenance Period) | Height | 0.75 Z-score | Standard Deviation 0.88 |
| SAVI | Change From Baseline in Growth Velocity (Height and Weight Z Score) (Primary Treatment and Maintenance Period) | Weight | 1.17 Z-score | Standard Deviation 0.03 |
| Aicardi-Goutières Syndrome (AGS) | Change From Baseline in Growth Velocity (Height and Weight Z Score) (Primary Treatment and Maintenance Period) | Height | 0.13 Z-score | Standard Deviation 1.17 |
| Aicardi-Goutières Syndrome (AGS) | Change From Baseline in Growth Velocity (Height and Weight Z Score) (Primary Treatment and Maintenance Period) | Weight | 0.46 Z-score | Standard Deviation 1.16 |
Secondary
Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment and Maintenance Period)
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.
Time frame: Baseline, 206.1 weeks
Population: AGS: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in Mean Daily Diary Scores in Participants With AGS (Primary Treatment and Maintenance Period) | -0.08 score on a scale | Standard Deviation 0.114 |
Secondary
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment and Maintenance Period)
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.
Time frame: Baseline, 191.1 weeks
Population: CANDLE: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE (Primary Treatment and Maintenance Period) | -0.24 score on a scale | Standard Deviation 0.613 |
Secondary
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment and Maintenance Period)
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.
Time frame: Baseline, 202.9 weeks
Population: SAVI: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in Mean Daily Diary Scores in Participants With SAVI (Primary Treatment and Maintenance Period) | -0.286 score on a scale | Standard Deviation 0.333 |
Secondary
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period)
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.
Time frame: Baseline, 206.1 weeks
Population: AGS: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period) | Crying | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period) | Excessive Irritability | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period) | Fever | -0.071 score on a scale | Standard Deviation 0.101 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period) | Generalized Seizure | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period) | Length of Uninterrupted Sleep | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period) | Neurologic Disability | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period) | Skin Findings (Body) | -0.5 score on a scale | Standard Deviation 0.707 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment and Maintenance Period) | Skin Findings on (Hands, Feet, Ears) | -0.071 score on a scale | Standard Deviation 0.101 |
Secondary
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period)
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.
Time frame: Baseline, 32 weeks
Population: AGS: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period) | Crying | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period) | Excessive Irritability | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period) | Fever | -0.071 score on a scale | Standard Deviation 0.101 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period) | Generalized Seizure | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period) | Length of Uninterrupted Sleep | 0.286 score on a scale | Standard Deviation 0.404 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period) | Neurologic Disability | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period) | Skin Findings (Body) | -0.5 score on a scale | Standard Deviation 0.707 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS (Primary Treatment Period) | Skin Findings (Hands, Feet, Ears) | -0.071 score on a scale | Standard Deviation 0.101 |
Secondary
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)
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.
Time frame: Baseline, 191.1 weeks
Population: CANDLE: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period) | Fatigue | -0.057 score on a scale | Standard Deviation 1.172 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period) | Fever | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period) | Headache | 0.057 score on a scale | Standard Deviation 0.128 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period) | Musculo-skeletal Pain | -0.514 score on a scale | Standard Deviation 1.128 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period) | Rash | -0.686 score on a scale | Standard Deviation 0.842 |
Secondary
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period)
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.
Time frame: Baseline, 20 weeks
Population: CANDLE: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period) | Fatigue | -0.029 score on a scale | Standard Deviation 0.997 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period) | Fever | 0 score on a scale | Standard Deviation 0 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period) | Headache | 0.057 score on a scale | Standard Deviation 0.128 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period) | Musculo-skeletal Pain | -0.514 score on a scale | Standard Deviation 1.128 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE (Primary Treatment Period) | Rash | -0.6 score on a scale | Standard Deviation 0.894 |
Secondary
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period)
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.
Time frame: Baseline, 202.9 weeks
Population: SAVI: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period) | Fatigue | -0.381 score on a scale | Standard Deviation 0.541 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period) | Fever | -0.095 score on a scale | Standard Deviation 0.165 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period) | Musculo-skeletal Pain | -0.238 score on a scale | Standard Deviation 0.412 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period) | Rash | -0.333 score on a scale | Standard Deviation 0.577 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period) | Respiratory / Breathing Symptoms | -0.667 score on a scale | Standard Deviation 1.155 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment and Maintenance Period) | Ulcers / Ischemic Lesions | 0 score on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period)
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.
Time frame: Baseline, 32 weeks
Population: SAVI: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period) | Fatigue | -0.381 score on a scale | Standard Deviation 0.541 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period) | Fever | -0.095 score on a scale | Standard Deviation 0.165 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period) | Musculo-skeletal Pain | -0.238 score on a scale | Standard Deviation 0.412 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period) | Rash | -0.333 score on a scale | Standard Deviation 0.577 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period) | Respiratory / Breathing Symptoms | -0.333 score on a scale | Standard Deviation 0.577 |
| CANDLE | Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI (Primary Treatment Period) | Ulcers / Ischemic Lesions | 0 score on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE (Primary Treatment and Maintenance Period)
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.
Time frame: Baseline, 191.1 weeks
Population: CANDLE: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE (Primary Treatment and Maintenance Period) | -2.6 score on a scale | Standard Deviation 2.07 |
Secondary
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE (Primary Treatment Period)
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.
Time frame: Baseline, 20 weeks
Population: CANDLE: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE (Primary Treatment Period) | -2.1 score on a scale | Standard Deviation 0.82 |
Secondary
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Maintenance Period)
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.
Time frame: SAVI: Baseline, 202.9 weeks; AGS: Baseline, 206.1 weeks
Population: SAVI and AGS: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Maintenance Period) | -1.5 score on a scale | Standard Deviation 1.73 |
| SAVI | Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Maintenance Period) | -3.75 score on a scale | Standard Deviation 3.89 |
Secondary
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Primary Treatment Period)
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.
Time frame: Baseline, 32 weeks
Population: SAVI and AGS: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Primary Treatment Period) | -1.33 score on a scale | Standard Deviation 1.76 |
| SAVI | Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS (Primary Treatment Period) | -3 score on a scale | Standard Deviation 3.54 |
Secondary
Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)
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.
Time frame: Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks
Population: CANDLE: All participants who received at least one dose of study drug. SAVI and AGS did not have Pre-treatment period data therefore only CANDLE cohort data were collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE (Primary Treatment and Maintenance Period) | 0.038 score on a scale | Standard Deviation 0.464 |
Secondary
Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE (Primary Treatment Period)
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.
Time frame: Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks
Population: CANDLE: All participants who received at least one dose of study drug. SAVI and AGS did not have Pre-treatment period data therefore only CANDLE cohort data were collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE (Primary Treatment Period) | 0.061 score on a scale | Standard Deviation 0.432 |
Secondary
Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE (Primary Treatment and Maintenance Period)
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.
Time frame: Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks
Population: CANDLE: All participants who received at least one dose of study drug. SAVI and AGS did not have Pre-treatment period data therefore only CANDLE cohort data were collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE (Primary Treatment and Maintenance Period) | -2.25 score on a scale | Standard Deviation 1.79 |
Secondary
Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE (Primary Treatment Period)
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.
Time frame: Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks
Population: CANDLE: All participants who received at least one dose of study drug. SAVI and AGS did not have Pre-treatment period data therefore only CANDLE cohort data were collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CANDLE | Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE (Primary Treatment Period) | -1.75 score on a scale | Standard Deviation 0.83 |
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 (Primary Treatment and Maintenance Period)
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.
Time frame: Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks
Population: CANDLE: All enrolled participants who received at least one dose of study drug. SAVI and AGS did not have Pre-treatment period data therefore only CANDLE cohort data were collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 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 (Primary Treatment and Maintenance Period) | 2.0 Percentage of Days | Standard Deviation 47.1 |
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 (Primary Treatment Period)
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
Time frame: Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks
Population: CANDLE: All enrolled participants who received at least one dose of study drug. SAVI and AGS did not have Pre-treatment period data therefore only CANDLE cohort data were collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 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 (Primary Treatment Period) | 4.4 Percentage of Days | Standard Deviation 48.7 |
Secondary
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment and Maintenance Period)
Decrease was defined as total steroid dose \<0.15 mg/kg/day (prednisone-equivalent) or \>=50% decrease from baseline.
Time frame: CANDLE: Week 191.1; SAVI: 202.9 and AGS: Week 206.1
Population: CANDLE, SAVI and AGS: All enrolled participants who received at least one dose of study drug and took corticosteroids at baseline with evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CANDLE | Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment and Maintenance Period) | 3 participants |
| SAVI | Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment and Maintenance Period) | 1 participants |
| Aicardi-Goutières Syndrome (AGS) | Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment and Maintenance Period) | 1 participants |
Secondary
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment Period)
Decrease was defined as total steroid dose at the visit \<0.15 mg/kg/day (prednisone-equivalent) or \>=50% decrease from baseline.
Time frame: CANDLE: Week 20, SAVI and AGS: Week 32
Population: CANDLE, SAVI and AGS: All enrolled participants who received at least one dose of study drug and took corticosteroids at baseline with evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CANDLE | Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment Period) | 4 participants |
| SAVI | Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment Period) | 1 participants |
| Aicardi-Goutières Syndrome (AGS) | Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE, SAVI and AGS (Primary Treatment Period) | 1 participants |