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

Primary Purpose

Nakajo-Nishimura Syndrome, Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome, STING-Associated Vasculopathy With Onset in Infancy

Status

Active

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

Baricitinib

About this trial

This is an interventional treatment trial for Nakajo-Nishimura Syndrome focused on measuring Nakajo-Nishimura Syndrome, CANDLE, SAVI, AGS

Eligibility Criteria

6 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Hiroshima University Hospital
Nara Medical University Hospital
Tokyo Medical And Dental University Medical Hospital
National Center For Child Health And Development
Wakayama Medical University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Baricitinib

Arm Description

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).

Outcomes

Primary Outcome Measures

Change From Baseline in Mean Daily Diary Scores in Participants With SAVI

Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For SAVI, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, fatigue, respiratory/breathing problems, and ulcers/ischemic lesions in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms,3 = more severe symptoms, and 4 = severe symptoms [equivalent to "worst" symptoms].The mean daily score range was 0-4 with the higher score indicating a more severe symptom. Total score was not utilized.

Change From Baseline in Mean Daily Diary Scores in Participants With AGS

For AGS, participant or caregiver was instructed to rate each symptom (rating) (neurologic disability (0, 5, 7,10) crying (0, 1, 2, 3), length of uninterrupted sleep (0, 1, 2, 3), generalized seizure (0, 8), fever (0,1), excessive irritability (0, 1, 2, 3), skin findings(body) (0, 1, 2, 3), and skin findings (hands, feet, and ears) (0, 1, 2, 3) with a higher score for each symptom indicating a more severe symptom. The mean daily diary score was the average of all symptom scores and the range was 0 - 4.25 with the higher score indicating a more severe symptom. Total score was not utilized.

Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE

Diaries were specific to individual indications or conditions (ie, NNS/CANDLE,SAVI, or AGS). For NNS/CANDLE, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, headache and fatigue in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms [equivalent to "worst" symptoms]. The mean daily score range was 0-4 with the higher score indicating a more severe symptom.

Secondary Outcome Measures

Change From Baseline in Mean Daily Diary Scores

Change from Baseline in Mean Daily Diary Scores

Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With SAVI and AGS

Decrease was defined as total steroid dose at the visit <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline.

Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE

Decrease was defined as total steroid dose at the visit <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline.

Number of Participants With Decrease in Daily Dose of Corticosteroids

Number of participants with decrease in Daily Dose of Corticosteroids

Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI

Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For SAVI, participant or caregiver was instructed to rate each symptom (fever, rash, musculoskeletal pain, fatigue, respiratory/breathing problems, and ulcers/ischemic lesions in the diary on a scale from 0 to 4 (where a score of 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = more severe symptoms, and 4 = severe symptoms [equivalent to "worst" symptoms]. The mean daily score range was 0-4 with the higher score indicating a more severe symptom.

Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS

Diaries were specific to individual indications or conditions (i.e. NNS/CANDLE, SAVI, or AGS). For AGS, participant or caregiver was instructed to rate each symptom (rating) (neurologic disability (0, 5, 7,10) crying (0, 1, 2, 3), length of uninterrupted sleep (0, 1, 2, 3), generalized seizure (0, 8), fever (0,1), excessive irritability (0, 1, 2, 3), skin findings(body) (0, 1, 2, 3), and skin findings (hands, feet, and ears) (0, 1, 2, 3) with a higher score for each symptom indicating a more severe symptom.

Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE

Change From Baseline in Patient's Symptom Specific Daily Diary Scores

Change from Baseline in Patient's Symptom Specific Daily Diary Scores

Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS

The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle VAS ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity".

Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE

The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle Visual Analog Scale (VAS) ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity".

Change From Baseline in the Physician's Global Assessment of Disease Activity Scores

Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5 Compared to That in Pre-treatment Period in Participants With CANDLE

Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5 Compared to that in Pre-treatment period in Participants With CANDLE

Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5

Change in Growth Velocity

Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE

Change From Pre-treatment Period in Mean Daily Diary Scores

Change from Pre-treatment period in Mean Daily Diary Scores

Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE

The Physician's Global Assessment of Disease Activity is used to assess the patient's current disease activity, as it relates to their signs and symptoms. The instrument uses a 21-circle Visual Analog Scale (VAS) ranging from 0 to 10 (using 0.5 increments) where 0 = "no activity" and 10 = "maximum activity" (Filocamo et al. 2010).

Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores

Change from Pre-treatment period in the Physician's Global Assessment of Disease Activity Scores

Full Information

NCT ID

NCT04517253

First Posted

August 17, 2020

Last Updated

November 28, 2022

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT04517253

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 27, 2020 (Actual)

Primary Completion Date

October 12, 2021 (Actual)

Study Completion Date

April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nakajo-Nishimura Syndrome, Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome, STING-Associated Vasculopathy With Onset in Infancy, Aicardi Goutieres Syndrome

Keywords

Nakajo-Nishimura Syndrome, CANDLE, SAVI, AGS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Baricitinib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Baricitinib

Other Intervention Name(s)

LY3009104

Intervention Description

Administered orally

Primary Outcome Measure Information:

Title

Change From Baseline in Mean Daily Diary Scores in Participants With SAVI

Description

Time Frame

Baseline, up to 32 weeks

Title

Change From Baseline in Mean Daily Diary Scores in Participants With AGS

Description

Time Frame

Baseline, up to 32 weeks

Title

Change From Baseline in Mean Daily Diary Scores in Participants With CANDLE

Description

Time Frame

Baseline, up to 20 weeks

Secondary Outcome Measure Information:

Title

Change From Baseline in Mean Daily Diary Scores

Description

Change from Baseline in Mean Daily Diary Scores

Time Frame

Baseline, up to 172 weeks

Title

Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With SAVI and AGS

Description

Decrease was defined as total steroid dose at the visit <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline.

Time Frame

Week 32

Title

Number of Participants With Decrease in Daily Dose of Corticosteroids in Participants With CANDLE

Description

Decrease was defined as total steroid dose at the visit <0.15 mg/kg/day (prednisone-equivalent) or >=50% decrease from baseline.

Time Frame

Week 20

Title

Number of Participants With Decrease in Daily Dose of Corticosteroids

Description

Number of participants with decrease in Daily Dose of Corticosteroids

Time Frame

Baseline, up to 172 weeks

Title

Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With SAVI

Description

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.

Time Frame

Baseline, up to 32 weeks

Title

Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With AGS

Description

Time Frame

Baseline, up to 32 weeks

Title

Change From Baseline in Patient's Symptom Specific Daily Diary Scores For Participants With CANDLE

Description

Time Frame

Baseline, up to 20 weeks

Title

Change From Baseline in Patient's Symptom Specific Daily Diary Scores

Description

Change from Baseline in Patient's Symptom Specific Daily Diary Scores

Time Frame

Baseline, up to 172 weeks

Title

Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With SAVI and AGS

Description

Time Frame

Baseline, up to 32 weeks

Title

Change From Baseline in the Physician's Global Assessment of Disease Activity Scores in Participants With CANDLE

Description

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".

Time Frame

Baseline, up to 20 weeks

Title

Change From Baseline in the Physician's Global Assessment of Disease Activity Scores

Description

Change From Baseline in the Physician's Global Assessment of Disease Activity Scores

Time Frame

Baseline, up to 172 weeks

Title

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

Description

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

Title

Change of Percentage of Days Meeting the Criteria of Participant's Mean Daily Diary Score <0.5

Description

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

Title

Change in Growth Velocity

Description

Change in Growth Velocity

Time Frame

Baseline, up to 172 weeks

Title

Change From Pre-treatment Period in Mean Daily Diary Scores For Participants With CANDLE

Description

Time Frame

Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks

Title

Change From Pre-treatment Period in Mean Daily Diary Scores

Description

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

Title

Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores For Participants With CANDLE

Description

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).

Time Frame

Pre-treatment period (average of 12-week pre-treatment data), up to 20 weeks

Title

Change From Pre-treatment Period in the Physician's Global Assessment of Disease Activity Scores

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Have systemic signs and symptoms of inflammation as manifested NNS/CANDLE, SAVI, AGS Have been diagnosed with genetic diagnosis Men must agree to use a reliable method of birth control during the study Women not of child-bearing potential or nonbreastfeeding Women must agree to use birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment NNS/CANDLE and SAVI patients who are ≥17.5 months of age AGS patients who are ≥6 months of age Are ≥ 5kg in body weight Exclusion Criteria: Have received immunosuppressive biologic agent/monoclonal antibody/oral JAK inhibitor/OAT3 inhibitor and cannot discontinue prior to investigational product initiation. Note: A washout period is required to each drug. Have diagnosis of current active tuberculosis (TB) or, latent TB who did not receive appropriate treatment. Have had a serious infection within 12 weeks prior to screening. Have a history of lymphoproliferative disease Have any history of venous thromboembolic event (VTE) (deep vein thrombosis [DVT]/pulmonary embolism [PE]) prior to screening. Have had any major surgery within 8 weeks prior to screening. Have previously been enrolled in any other study investigating baricitinib.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

Hiroshima University Hospital

City

Hiroshima-shi

State/Province

Hiroshima-ken

ZIP/Postal Code

734-8551

Country

Japan

Facility Name

Nara Medical University Hospital

City

Kashihara

State/Province

Nara

ZIP/Postal Code

634-8522

Country

Japan

Facility Name

Tokyo Medical And Dental University Medical Hospital

City

Bunkyō

State/Province

Tokyo

ZIP/Postal Code

113-8519

Country

Japan

Facility Name

National Center For Child Health And Development

City

Setagaya-ku

State/Province

Tokyo

ZIP/Postal Code

157-8535

Country

Japan

Facility Name

Wakayama Medical University Hospital

City

Wakayama

ZIP/Postal Code

641-8510

Country

Japan

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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 URL

http://vivli.org/

Links:

URL

https://trials.lillytrialguide.com/en-US/trial/4deb45sM6OlbQ6MBzCAx6H

Description

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

Learn more about this trial

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

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