Uveitis
Conditions
Brief summary
The reason for this study is to see if the study drug baricitinib given orally is safe and effective in participants with active juvenile idiopathic arthritis (JIA)-associated uveitis or chronic anterior antinuclear antibody-positive uveitis from 2 years to less than 18 years old.
Interventions
DRUGBaricitinib
Administered orally
DRUGAdalimumab
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have a diagnosis of JIA-U or chronic anterior antinuclear antibody (ANA) positive uveitis without systemic features. * Participants must have active anterior uveitis, defined as cellular infiltrate in the anterior chamber of SUN criteria grade ≥1+ at screening and randomization, despite prior treatment with adequate doses of topical steroid therapy and methotrexate (MTX). * Participants must have an inadequate response or intolerance to MTX. * Participants must be on a stable dose of corticosteroid eye drops for at least 2 weeks prior to screening with a maximum of 4 drops/day/eye at screening. * Participants and their partners of child bearing potential must agree to use 2 effective methods of contraception for the duration of the study and for at least 1 week following the last dose of investigational product.
Exclusion criteria
* Participants must not have a history or presence of any autoimmune inflammatory condition other than JIA, such as Crohn's disease or ulcerative colitis. * Participants must not have any contraindications to adalimumab. * Exception: Participants who are biologic disease-modifying antirheumatic drug (bDMARD) inadequate response or intolerance with a contraindication to adalimumab may be enrolled, as they will be assigned to baricitinib. * Participants must not have increased intraocular pressure ≥25 millimeters of mercury (mm Hg) or that required treatment, including increases in medications, surgery, or hospitalization, within 4 weeks prior to baseline that, in the opinion of the investigator, would pose an unacceptable risk to the participant. * Participants must not have had intraocular surgery within the 3 months prior to screening (such as for cataract(s), glaucoma or vitrectomy). * Participants must not have a current or recent (\<4 weeks prior to baseline) infection. * Participants must not have a positive test for hepatitis B virus (HBV) at screening. * Participants must not have evidence of active tuberculosis (TB) or untreated latent TB.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of Responders for Baricitinib at Week 24 | Week 24 | Response was defined according to the Standardization of Uveitis Nomenclature (SUN) criteria as a 2-step decrease in the level of inflammation (anterior chamber cells) or decrease to zero through week 24, in the eye most severely affected at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in SUN Grade of Cells in the Anterior Chamber in the Most Severely Affected Eye | Baseline, Week 24 | Change from Baseline in SUN Grade of Cells in the Anterior Chamber in the Most Severely Affected Eye. Outcome data will be provided after the study is completed. |
| Change From Baseline in SUN Grade of Cells in the Anterior Chamber in the Less Severely Affected Eye (If Applicable) | Baseline, Week 24 | Change from Baseline in SUN Grade of Cells in the Anterior Chamber in the Less Severely Affected Eye (If Applicable). Outcome data will be provided after the study is completed. |
| Percentage of Responders in Participants With Bilateral Uveitis Disease at Baseline | Week 24 | Response is defined according to the SUN criteria as a 2-step decrease in the level of anterior chamber cells in the most severely affected eye at baseline (or both eyes if the inflammation grade is the same in both eyes) and a 1-step decrease in the level of anterior chamber cells in the less severely affected eye at baseline. Outcome data will be provided after the study is completed. |
| Change From Baseline in Visual Acuity Measured by Age-Appropriate Logarithm of the Minimum Angle of Resolution (LogMAR) Test | Baseline, Week 24 | Change from Baseline in Visual Acuity Measured by Age-Appropriate LogMAR Test. Outcome data will be provided after the study is completed. |
| Change From Baseline in Vitreous Haze | Baseline, Week 24 | Change from Baseline in Vitreous Haze. Outcome data will be provided after the study is completed. |
| Change From Baseline in Grade of Flare in the Anterior Chamber | Baseline, Week 24 | Change from Baseline in Grade of Flare in the Anterior Chamber. Outcome data will be provided after the study is completed. |
| Percentage of Participants With Inactive Anterior Uveitis (Using SUN Definition) | Week 24 | Percentage of Participants with Inactive Anterior Uveitis (using SUN Definition). Outcome data will be provided after the study is completed. |
| Time to Inactive Anterior Uveitis Disease (Using SUN Definition) | Baseline through Week 24 | Time to Inactive Anterior Uveitis Disease (Using SUN Definition). Outcome data will be provided after the study is completed. |
| Percentage of Participants Who Are Able to Taper Concomitant Topical Corticosteroids to <2 Drops Per Day | Week 24 | Percentage of Participants who are Able to Taper Concomitant Topical Corticosteroids to \<2 Drops Per Day. Outcome data will be provided after the study is completed. |
| Pediatric American College of Rheumatology (PediACR30) Response Rate (For Participants With JIA-U) | Week 24 | PediACR30 Response Rate (For Participants with JIA-U). Outcome data will be provided after the study is completed. |
| Change From Baseline in Overall Uveitis-Related Disability | Baseline, Week 24 | Change from Baseline in Overall Uveitis-Related Disability. Outcome data will be provided after the study is completed. |
Countries
France, Germany, Italy, Spain, United Kingdom
Contacts
STUDY_DIRECTORCall 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
Participant flow
Recruitment details
Overall, 30 participants were enrolled in the study. One participant (in baricitinib arm) withdrew from the study before administration of the study drug. This study is conducted in 2 parts. Part A (24 weeks) and Part B (260 weeks). Participants assigned to baricitinib and completed the Part A as a responder continued receiving baricitinib until the end of study or discontinuation from the study.
Participants by arm
| Arm | Count |
|---|---|
| Baricitinib Participants ≥9 to \<18 years of age were administered 4 mg baricitinib QD. Participants \<9 years of age were administered 2 mg baricitinib QD.
Participants \<6 years of age received an oral suspension. Participants ≥6 to \<12 years of age had the option of receiving an oral suspension. Participants \>12 years of age were supplied tablets. | 24 |
| Adalimumab Participants received adalimumab administered SC once every 2 weeks. The dose was based on body weight: 20 mg every 2 weeks for participants weighing \<30 kg, or 40 mg every 2 weeks for participants weighing ≥30 kg. | 5 |
| Total | 29 |
Baseline characteristics
| Characteristic | Baricitinib | Adalimumab | Total |
|---|---|---|---|
| Age, Continuous | 11.60 years STANDARD_DEVIATION 3.53 | 6.60 years STANDARD_DEVIATION 2.51 | 10.70 years STANDARD_DEVIATION 3.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 4 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 20 Participants | 4 Participants | 24 Participants |
| Region of Enrollment France | 4 Participants | 0 Participants | 4 Participants |
| Region of Enrollment Germany | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Italy | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Spain | 3 Participants | 0 Participants | 3 Participants |
| Region of Enrollment United Kingdom | 13 Participants | 2 Participants | 15 Participants |
| Sex: Female, Male Female | 14 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 10 Participants | 0 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 5 |
| other Total, other adverse events | 16 / 24 | 4 / 5 |
| serious Total, serious adverse events | 2 / 24 | 1 / 5 |
Outcome results
Primary
Part A: Percentage of Responders for Baricitinib at Week 24
Response was defined according to the Standardization of Uveitis Nomenclature (SUN) criteria as a 2-step decrease in the level of inflammation (anterior chamber cells) or decrease to zero through week 24, in the eye most severely affected at baseline.
Time frame: Week 24
Population: All participants who received at least one dose of baricitinib in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Baricitinib | Part A: Percentage of Responders for Baricitinib at Week 24 | 33.3 Percentage of participants |
Secondary
Change From Baseline in Grade of Flare in the Anterior Chamber
Change from Baseline in Grade of Flare in the Anterior Chamber. Outcome data will be provided after the study is completed.
Time frame: Baseline, Week 24
Secondary
Change From Baseline in Overall Uveitis-Related Disability
Change from Baseline in Overall Uveitis-Related Disability. Outcome data will be provided after the study is completed.
Time frame: Baseline, Week 24
Secondary
Change From Baseline in SUN Grade of Cells in the Anterior Chamber in the Less Severely Affected Eye (If Applicable)
Change from Baseline in SUN Grade of Cells in the Anterior Chamber in the Less Severely Affected Eye (If Applicable). Outcome data will be provided after the study is completed.
Time frame: Baseline, Week 24
Secondary
Change From Baseline in SUN Grade of Cells in the Anterior Chamber in the Most Severely Affected Eye
Change from Baseline in SUN Grade of Cells in the Anterior Chamber in the Most Severely Affected Eye. Outcome data will be provided after the study is completed.
Time frame: Baseline, Week 24
Secondary
Change From Baseline in Visual Acuity Measured by Age-Appropriate Logarithm of the Minimum Angle of Resolution (LogMAR) Test
Change from Baseline in Visual Acuity Measured by Age-Appropriate LogMAR Test. Outcome data will be provided after the study is completed.
Time frame: Baseline, Week 24
Secondary
Change From Baseline in Vitreous Haze
Change from Baseline in Vitreous Haze. Outcome data will be provided after the study is completed.
Time frame: Baseline, Week 24
Secondary
Pediatric American College of Rheumatology (PediACR30) Response Rate (For Participants With JIA-U)
PediACR30 Response Rate (For Participants with JIA-U). Outcome data will be provided after the study is completed.
Time frame: Week 24
Secondary
Percentage of Participants Who Are Able to Taper Concomitant Topical Corticosteroids to <2 Drops Per Day
Percentage of Participants who are Able to Taper Concomitant Topical Corticosteroids to \<2 Drops Per Day. Outcome data will be provided after the study is completed.
Time frame: Week 24
Secondary
Percentage of Participants With Inactive Anterior Uveitis (Using SUN Definition)
Percentage of Participants with Inactive Anterior Uveitis (using SUN Definition). Outcome data will be provided after the study is completed.
Time frame: Week 24
Secondary
Percentage of Responders in Participants With Bilateral Uveitis Disease at Baseline
Response is defined according to the SUN criteria as a 2-step decrease in the level of anterior chamber cells in the most severely affected eye at baseline (or both eyes if the inflammation grade is the same in both eyes) and a 1-step decrease in the level of anterior chamber cells in the less severely affected eye at baseline. Outcome data will be provided after the study is completed.
Time frame: Week 24
Secondary
Time to Inactive Anterior Uveitis Disease (Using SUN Definition)
Time to Inactive Anterior Uveitis Disease (Using SUN Definition). Outcome data will be provided after the study is completed.
Time frame: Baseline through Week 24