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

February 29, 2024 updated by: Eli Lilly and Company

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

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).

Study Overview

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have systemic signs and symptoms of inflammation as manifested NNS/CANDLE, SAVI, AGS
  • Have been diagnosed with genetic diagnosis
  • Men must agree to use a reliable method of birth control during the study
  • Women not of child-bearing potential or nonbreastfeeding
  • Women must agree to use birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment
  • NNS/CANDLE and SAVI patients who are ≥17.5 months of age
  • AGS patients who are ≥6 months of age
  • Are ≥ 5kg in body weight

Exclusion Criteria:

  • Have received immunosuppressive biologic agent/monoclonal antibody/oral JAK inhibitor/OAT3 inhibitor and cannot discontinue prior to investigational product initiation. Note: A washout period is required to each drug.
  • Have diagnosis of current active tuberculosis (TB) or, latent TB who did not receive appropriate treatment.
  • Have had a serious infection within 12 weeks prior to screening.
  • Have a history of lymphoproliferative disease
  • Have any history of venous thromboembolic event (VTE) (deep vein thrombosis [DVT]/pulmonary embolism [PE]) prior to screening.
  • Have had any major surgery within 8 weeks prior to screening.
  • Have previously been enrolled in any other study investigating baricitinib.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Baricitinib

CANDLE:

Participants with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) received an optimized dosage of baricitinib that was determined throughout the dose-adjustment period administered as tablets or oral suspension based on participants weight and estimated glomerular filtration rate (eGFR).

SAVI:

Participants with STING-associated vasculopathy with onset during infancy (SAVI) received an optimized dosage of baricitinib that was determined throughout the dose-adjustment period administered as tablets or oral suspension based on participants weight and estimated glomerular filtration rate (eGFR).

Aicardi-Goutières Syndrome (AGS):

Participants with Aicardi-Goutières Syndrome (AGS) received an optimized dosage of baricitinib that was determined throughout the dose-adjustment period administered as tablets or oral suspension based on participants weight and estimated glomerular filtration rate (eGFR).

Administered orally
Other Names:
  • LY3009104

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Mean Daily Diary Scores in Participants With SAVI
Time Frame: Baseline, up to 32 weeks
Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For SAVI, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, fatigue, respiratory/breathing problems, and ulcers/ischemic lesions in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms,3 = more severe symptoms, and 4 = severe symptoms [equivalent to "worst" symptoms].The mean daily score range was 0-4 with the higher score indicating a more severe symptom. Total score was not utilized.
Baseline, up to 32 weeks
Change From Baseline in Mean Daily Diary Scores in Participants With AGS
Time Frame: Baseline, up to 32 weeks
For AGS, participant or caregiver was instructed to rate each symptom (rating) (neurologic disability (0, 5, 7,10) crying (0, 1, 2, 3), length of uninterrupted sleep (0, 1, 2, 3), generalized seizure (0, 8), fever (0,1), excessive irritability (0, 1, 2, 3), skin findings(body) (0, 1, 2, 3), and skin findings (hands, feet, and ears) (0, 1, 2, 3) with a higher score for each symptom indicating a more severe symptom. The mean daily diary score was the average of all symptom scores and the range was 0 - 4.25 with the higher score indicating a more severe symptom. Total score was not utilized.
Baseline, up to 32 weeks
Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE
Time Frame: Baseline, up to 20 weeks
Diaries were specific to individual indications or conditions (ie, NNS/CANDLE,SAVI, or AGS). For NNS/CANDLE, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, headache and fatigue in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms [equivalent to "worst" symptoms]. The mean daily score range was 0-4 with the higher score indicating a more severe symptom.
Baseline, up to 20 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Mean Daily Diary Scores
Time Frame: Baseline, up to 172 weeks
Change from Baseline in Mean Daily Diary Scores
Baseline, up to 172 weeks
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With SAVI and AGS
Time Frame: Week 32
Decrease was defined as total steroid dose at the visit <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline.
Week 32
Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE
Time Frame: Week 20
Decrease was defined as total steroid dose at the visit <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline.
Week 20
Number of Participants With Decrease in Daily Dose of Corticosteroids
Time Frame: Baseline, up to 172 weeks
Number of participants with decrease in Daily Dose of Corticosteroids
Baseline, up to 172 weeks
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI
Time Frame: Baseline, up to 32 weeks
Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For SAVI, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, fatigue, respiratory/breathing problems, and ulcers/ischemic lesions in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms [equivalent to "worst" symptoms]. The mean daily score range was 0-4 with the higher score indicating a more severe symptom.
Baseline, up to 32 weeks
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS
Time Frame: Baseline, up to 32 weeks
Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For AGS, participant or caregiver was instructed to rate each symptom (rating) (neurologic disability (0, 5, 7,10) crying (0, 1, 2, 3), length of uninterrupted sleep (0, 1, 2, 3), generalized seizure (0, 8), fever (0,1), excessive irritability (0, 1, 2, 3), skin findings(body) (0, 1, 2, 3), and skin findings (hands, feet, and ears) (0, 1, 2, 3) with a higher score for each symptom indicating a more severe symptom.
Baseline, up to 32 weeks
Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE
Time Frame: Baseline, up to 20 weeks
Diaries were specific to individual indications or conditions (ie, NNS/CANDLE,SAVI, or AGS). For NNS/CANDLE, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, headache and fatigue in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms [equivalent to "worst" symptoms]. The mean daily score range was 0-4 with the higher score indicating a more severe symptom.
Baseline, up to 20 weeks
Change From Baseline in Patient's Symptom Specific Daily Diary Scores
Time Frame: Baseline, up to 172 weeks
Change from Baseline in Patient's Symptom Specific Daily Diary Scores
Baseline, up to 172 weeks
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS
Time Frame: Baseline, up to 32 weeks
The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle VAS ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity".
Baseline, up to 32 weeks
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE
Time Frame: Baseline, up to 20 weeks
The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle Visual Analog Scale (VAS) ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity".
Baseline, up to 20 weeks
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores
Time Frame: Baseline, up to 172 weeks
Change From Baseline in the Physician's Global Assessment of Disease Activity Scores
Baseline, up to 172 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
Time Frame: 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
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
Time Frame: Pre-treatment period (average of 12-week pre-treatment data), up to 172 weeks
Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5
Pre-treatment period (average of 12-week pre-treatment data), up to 172 weeks
Change in Growth Velocity
Time Frame: Baseline, up to 172 weeks
Change in Growth Velocity
Baseline, up to 172 weeks
Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE
Time Frame: 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.
Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks
Change From Pre-treatment Period in Mean Daily Diary Scores
Time Frame: Pre-treatment period (average of 12-week pre-treatment data), up to 172 weeks
Change from Pre-treatment period in Mean Daily Diary Scores
Pre-treatment period (average of 12-week pre-treatment data), up to 172 weeks
Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE
Time Frame: 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).
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
Time Frame: Pre-treatment period (average of 12-week pre-treatment data), up to 172 weeks
Change from Pre-treatment period in the Physician's Global Assessment of Disease Activity Scores
Pre-treatment period (average of 12-week pre-treatment data), up to 172 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 27, 2020

Primary Completion (Actual)

October 12, 2021

Study Completion (Estimated)

April 30, 2025

Study Registration Dates

First Submitted

August 17, 2020

First Submitted That Met QC Criteria

August 17, 2020

First Posted (Actual)

August 18, 2020

Study Record Updates

Last Update Posted (Actual)

March 1, 2024

Last Update Submitted That Met QC Criteria

February 29, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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