Nakajo-Nishimura SyndromePhase 2/3NCT04517253

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

A Phase 2/3 study testing Baricitinib in people with Nakajo-Nishimura Syndrome and Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome, run by Eli Lilly and Company at 5 sites in Japan.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

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… Read more about this study

Who is it for?: Ages 6 months and older
Conditions the study is for: Nakajo-Nishimura Syndrome, Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome, STING-Associated Vasculopathy With Onset in Infancy
What is being tested?: Baricitinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 5 sitesJapan
Study dates: 27 Oct 2020to 28 Nov 2024
Phase: Phase 2/3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 months and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Japan5 sites

Tokyo Medical And Dental University Medical Hospital
Bunkyō, Tokyo, 113-8519
Hiroshima University Hospital
Hiroshima, 734-8551
Nara Medical University Hospital
Kashihara, Nara, 634-0813
National Center For Child Health And Development
Setagaya-ku, Tokyo, 157-8535
Wakayama Medical University Hospital
Wakayama, 641-0012

Other trials in Japan

About this study

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

Conditions: Nakajo-Nishimura Syndrome, Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome, STING-Associated Vasculopathy With Onset in Infancy, Aicardi Goutieres Syndrome
Being tested: Baricitinib
Keywords: Nakajo-Nishimura Syndrome, CANDLE, SAVI, AGS
Medical subject headings: Nakajo syndrome, Aicardi-Goutieres syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BaricitinibDrug
Also called LY3009104
Administered orally

Study groups in NCT04517253
Study group	Role	What they receive
CANDLE	Experimental	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. Receives: Drug: Baricitinib
SAVI	Experimental	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. Receives: Drug: Baricitinib
Aicardi-Goutières Syndrome (AGS)	Experimental	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. Receives: Drug: Baricitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, 20 weeks
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.
Measured: Baseline, 32 weeks
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.
Measured: Baseline, 32 weeks

Secondary outcomes (22)

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.
Measured: Baseline, 191.1 weeks
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.
Measured: Baseline, 202.9 weeks
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.
Measured: Baseline, 206.1 weeks
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.
Measured: 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)
Decrease was defined as total steroid dose <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline.
Measured: 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)
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.
Measured: Baseline, 20 weeks
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.
Measured: Baseline, 32 weeks
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.
Measured: Baseline, 32 weeks
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.
Measured: Baseline, 191.1 weeks
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.
Measured: Baseline, 202.9 weeks
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.
Measured: Baseline, 206.1 weeks
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: Pre-treatment period (average of 12-week pre-treatment data), up to 191.1 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Oct 202028 Nov 2024

First posted18 Aug 2020
Study start27 Oct 2020
Primary completion4 Apr 2023
Study completion28 Nov 2024

Why it stopped: The study was terminated due to efficacy/effectiveness reasons

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Nakajo-Nishimura SyndromeStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04517253
Sponsor's protocol ID: 17571
Other IDs: I4V-JE-JAJE, 2025-000001-16, 2025
Status last verified: Jun 2025
First submitted: 17 Aug 2020
Last updated: 10 Jul 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Publications

Kanazawa N, Ishii T, Takita Y, Nishikawa A, Nishikomori R. Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS). Pediatr Rheumatol Online J. 2023 Apr 22;21(1):38. doi: 10.1186/s12969-023-00817-8.
PubMed 37087470