Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis (STAR Study)

• Sponsor: National Eye Institute (NEI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02911116
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arms: 2
• Actual Duration (Months): 37.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Background:

Uveitis is an inflammation of the eye that can cause vision loss. It is treated with medications and sometimes surgery. However, in many people, treatment does not always prevent loss of vision. A new medication, ustekinumab, reduces inflammation in patients with other inflammatory diseases. Therefore, it might be helpful in treatment of uveitis.

Objective:

To see if ustekinumab is safe and can help people with uveitis.

Eligibility:

People ages 18 and older with uveitis

Design:

Participants will be screened with:

Medical and eye disease history

Physical exam

Eye exam: The pupil is dilated with eye drops. A machine scans the back of the eye. Pictures are taken of the inside of the eye.

Blood and urine tests

Tuberculosis test

Participants will have 6 clinic visits over 28 weeks. Visits lasts 2-3 hours and include:

• Medical and eye disease history

• Physical and eye exams

• Blood and urine tests

• Fluorescein angiography: A needle guides a thin plastic tube into an arm vein. A dye is injected into the tube. The dye travels through the veins up to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels in the eyes.

• Cohort 1 - Ustekinumab injections at Weeks 0, 4, and 8: The injection is under the skin of the upper arm, leg, or abdomen.

Participants will have their uveitis monitored and receive standard uveitis care during the study.

• Cohort 2 - Ustekinumab injections via intravenous (IV) injection at first visit, followed by a single 90 mg injection of ustekinumab under the skin of the upper arm, leg or abdomen. For the IV injection a needle will be used to guide a thin plastic tube (catheter) into one of the arm veins. The needle will be removed, leaving only the catheter in the vein.

Condition or Disease	Intervention/Treatment	Phase
Uveitis	Drug: Ustekinumab; Drug: Ustekinumab	Phase 2

Detailed Description

Objective: Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects and many patients continue to experience disease flare-ups. Ustekinumab is a human IL-12 and -23 antagonist. The involvement of IL-12 and IL-23 in the pathophysiology of uveitis and other autoimmune diseases known to be associated with uveitis suggests that ustekinumab could be a potential treatment for uveitis. The study objective is to investigate the safety, tolerability and potential efficacy of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis.

Study Population: The first cohort will consist of five participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria. The second cohort will include up to four participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria. Up to eleven participants may be enrolled, as up to two participants may be accrued in the second cohort to account for participants who withdraw from the study prior to Week 16.

Design: This is a prospective, non-randomized, uncontrolled, two-arm pilot study to evaluate of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis. Five participants in the first cohort will receive a 90 mg subcutaneous (SC) injection of ustekinumab at baseline and a second and third injection at Week 4 and 8 for a total of 3 injections. For the second cohort, up to four participants will receive an initial high, weight-based dose of ustekinumab via intravenous (IV) injection (up to 55 kg, 260 mg (2 vials); greater than 55 kg to 85 kg, 390 mg (3 vials); greater than 85 kg, 520 mg (4 vials)), followed by a single 90 mg subcutaneous injection at Week 8. In participants who demonstrate allergic reaction to the first dose, the second dose can also be administered as IV infusion with pre-infusion desensitization instead of a subcutaneous injection as it allows better control on the rate of drug administration. Participants will continue in the study for a total of 28 weeks and will be able to receive standard of care after the first 16 weeks.

Outcome Measures: For each cohort, the primary outcome is the number of participants who experience treatment response by Week 16. Secondary outcomes for each cohort include changes in visual acuity, the number of participants who experience a recurrence, the number of days to recurrence, presence or extent of macular edema, the amount of retino-vascular leakage, changes in retinal thickening, the length of time to quiescence and the ability to taper concomitant immunosuppressive medications. Safety outcomes for each cohort include the number and severity of systemic and ocular toxicities and adverse events, the proportion of participants who experience vision loss of greater than or equal to 15 letters as measured by Electronic Visual Acuity (EVA) and the number of participants who experience a substantial rise in elevated intraocular pressure (IOP).

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study to Investigate Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis
• Actual Study Start Date: Mar 30, 2017
• Actual Primary Completion Date: Mar 5, 2020
• Actual Study Completion Date: May 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 (Subcutaneous Only) Subcutaneous injections of Ustekinumab at baseline.	Drug: Ustekinumab; Subcutaneous Injection
Experimental: Cohort 2 (IV and Subcutaneous) Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection.	Drug: Ustekinumab; Subcutaneous Injection; Drug: Ustekinumab; Intravenous Infusion

Outcome Measures

Primary Outcome Measures

1. Number of Participants Experiencing a Treatment Response by Week 16 [Baseline to Week 16]

   The primary outcome is the number of participants in each cohort who experience a treatment response by Week 16. Treatment response is defined as experiencing all of the following for both/eligible eyes: no active inflammatory chorioretinal lesion and/or absent or decreased retinal vascular leakage; ≤ 0.5+ anterior chamber (AC) cells; ≤ 0.5+ vitreous haze.

Secondary Outcome Measures

1. Mean Change in Visual Acuity in the Right Eye at All Follow-up Visits Compared to Baseline [Baseline to Week 4, Week 8, Week 12, Week 16, Week 28]

   Mean change in visual acuity in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline as measured by electronic visual acuity (EVA).

2. Mean Change in Visual Acuity in the Left Eye at All Follow-up Visits Compared to Baseline [Baseline to Week 4, Week 8, Week 12, Week 16, Week 28]

   Mean change in visual acuity in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline as measured by electronic visual acuity (EVA).

3. Median Change in Visual Acuity in the Right Eye at All Follow-up Visits Compared to Baseline [Baseline to Week 4, Week 8, Week 12, Week 16, Week 28]

   Median change in visual acuity in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline as measured by electronic visual acuity (EVA).

4. Median Change in Visual Acuity in the Left Eye at All Follow-up Visits Compared to Baseline [Baseline to Week 4, Week 8, Week 12, Week 16, Week 28]

   Median change in visual acuity in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline as measured by electronic visual acuity (EVA).

5. Number of Participants Who Experience a Recurrence of Uveitis at All Follow-up Visits [Week 4, Week 8, Week 12, Week 16]

   Number of participants in each cohort who experience a recurrence of uveitis at each follow-up visit (Week 4, Week 8, Week 12, and Week 16). Recurrence of uveitis is defined as the presence of one of the following in at least one eye: 1) new active inflammatory chorioretinal lesion and/or retinal vascular leakage; 2) a 2+ increase in anterior chamber (AC) cells relative to Baseline; 3) a 2-step increase in vitreous haze (VH) relative to Baseline; 4) worsening of best-corrected visual acuity (BCVA) by ≥ 15 letters relative to Baseline.

6. Mean Number of Days Until First Recurrence [Baseline to Week 16]

   Mean number of days following the baseline injection until first recurrence (of the participants who recur). Recurrence of uveitis is defined as the presence of one of the following in at least one eye: 1) new active inflammatory chorioretinal lesion and/or retinal vascular leakage; 2) a 2+ increase in anterior chamber (AC) cells relative to Baseline; 3) a 2-step increase in vitreous haze (VH) relative to Baseline; 4) worsening of best-corrected visual acuity (BCVA) by ≥ 15 letters relative to Baseline.

7. Median Number of Days Until First Recurrence [Baseline to Week 16]

   Median number of days following the baseline injection until first recurrence (of the participants who recur). Recurrence of uveitis is defined as the presence of one of the following in at least one eye: 1) new active inflammatory chorioretinal lesion and/or retinal vascular leakage; 2) a 2+ increase in anterior chamber (AC) cells relative to Baseline; 3) a 2-step increase in vitreous haze (VH) relative to Baseline; 4) worsening of best-corrected visual acuity (BCVA) by ≥ 15 letters relative to Baseline.

8. Presence or Extent of Macular Edema as Determined by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits [Week 4, Week 8, Week 12, Week 16, Week 28]

   Presence or extent of macular edema as determined by optical coherence tomography (OCT) in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants that did and did not have macular edema present is presented.

9. Presence or Extent of Macular Edema as Determined by Optical Coherence Tomography (OCT) in the Left Eye at All Follow-up Visits [Week 4, Week 8, Week 12, Week 16, Week 28]

   Presence or extent of macular edema as determined by optical coherence tomography (OCT) in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants that did and did not have macular edema present is presented.

10. Presence or Extent of Macular Edema as Determined by Fluorescein Angiogram (FA) in the Right Eye at All Follow-up Visits [Week 4, Week 8, Week 12, Week 16, Week 28]

    Presence or extent of macular edema as determined by fluorescein angiogram (FA) in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants that did and did not have macular edema present is presented.

11. Presence or Extent of Macular Edema as Determined by Fluorescein Angiogram (FA) in the Left Eye at All Follow-up Visits [Week 4, Week 8, Week 12, Week 16, Week 28]

    Presence or extent of macular edema as determined by fluorescein angiogram (FA) in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants that did and did not have macular edema present is presented.

12. Amount of Retino-vascular Leakage as Measured by Fluorescein Angiogram (FA) in the Right Eye at All Follow-up Visits [Week 4, Week 8, Week 12, Week 16, Week 28]

    Amount of retino-vascular leakage as measured by fluorescein angiogram (FA) in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants experiencing presence and new/increased lesions, presence and decreased lesions, presence and no new/increased or decreased lesions, and absence of lesions are presented.

13. Amount of Retino-vascular Leakage as Measured by Fluorescein Angiogram (FA) in the Left Eye at All Follow-up Visits [Week 4, Week 8, Week 12, Week 16, Week 28]

    Amount of retino-vascular leakage as measured by fluorescein angiogram (FA) in the left eye at all follow-up visits (Week 4, week 8, Week 12, Week 16, and Week 28). The number of participants experiencing presence and new/increased lesions, presence and decreased lesions, presence and no new/increased or decreased lesions, and absence of lesions are presented.

14. Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits Compared to Baseline [Baseline to Week 4, Week 8, Week 12, Week 16, Week 28]

    Mean change in central retinal thickness as measured by optical coherence tomography (OCT) in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline.

15. Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Left Eye at All Follow-up Visits Compared to Baseline [Baseline to Week 4, Week 8, Week 12, Week 16, Week 28]

    Mean change in central retinal thickness as measured by optical coherence tomography (OCT) in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline.

16. Length of Time to Quiescence in the Right Eye [Baseline to Week 16]

    Mean length of time to first experience of quiescence in the right eye. Quiescence refers to absence of active disease defined as not having the following conditions: +1 or more vitreous haze; and/or active chorioretinitis or leakage on fluorescein angiogram (FA) (that is more than one quadrant) that requires treatment.

17. Length of Time to Quiescence in the Left Eye [Baseline to Week 16]

    Mean length of time to first experience of quiescence in the left eye. Quiescence refers to absence of active disease defined as not having the following conditions: +1 or more vitreous haze; and/or active chorioretinitis or leakage on fluorescein angiogram (FA) (that is more than one quadrant) that requires treatment.

18. Ability to Taper Concomitant Immunosuppressive Medications [Baseline to Week 28]

    The number of participants able to taper concomitant immunosuppressive medications.

Other Outcome Measures

1. Number of Participants Experiencing a Clinically Significant Increase in Elevated Intraocular Pressure (IOP) at Any Follow-up Visit [Week 4, Week 8, Week 12, Week 16, Week 28]

   Number of participants experiencing a clinically significant increase in elevated intraocular pressure (IOP) at any follow-up visit in either eye. An increase in IOP ≥10 mmHg as compared with baseline is considered a clinically significant increase.

2. Proportion of Participants With ≥15 Letter Loss at Any Follow-up Visit. [Week 4, Week 8, Week 12, Week 16, Week 28]

   Proportion of participants with ≥15 letter loss in best-corrected visual acuity (BCVA) from baseline at any follow-up visit in either eye.

3. Number and Severity of Systemic and Ocular Toxicities and Adverse Events [Baseline to Week 28]

   Number and severity of systemic and ocular toxicities and adverse events for participants in both cohorts. Severity of each event is classified as mild, moderate, or severe. Natural progression of disease adverse events are not included.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

-INCLUSION CRITERIA:

1. Participant has the ability to understand and sign the informed consent document.

2. Participant is 18 years of age or older.

3. Participant has negative purified protein derivative (PPD) or quantiferon testing done within three months prior to enrollment or had latent tuberculosis (TB) but has completed prophylactic anti-TB treatment.

4. Participant has active intermediate uveitis, posterior uveitis or panuveitis in at least one eye requiring systemic therapy. Active disease is defined as:

• +1 or more vitreous haze (according to Standardization of Uveitis Nomenclature (SUN) criteria) AND/OR

• Active chorioretinitis or leakage on Fluorescein angiography (FA)(that is in more than one quadrant) that requires treatment.

1. Participant has visual acuity in at least one eye of 20/400 or better.

2. Participant is willing and able to comply with the study procedures.

3. Female participants of childbearing potential must not be pregnant or breast-feeding, have a negative pregnancy test at screening and must be willing to undergo pregnancy testing throughout the study.

4. Both female participants of childbearing potential and male participants able to father a child must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two effective methods of contraception throughout the course of the study and for six weeks after the last investigational product injection. Acceptable methods of contraception for this study include:

• hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),

• intrauterine device,

• barrier methods (diaphragm, condom) with spermicide, or

• surgical sterilization (tubal ligation).

EXCLUSION CRITERIA:

1. Participant has a significant active infection (an infection requiring treatment as determined by the medical team), including active tuberculosis or human immunodeficiency virus (HIV).

2. Participant received a live vaccination within the past six weeks.

3. Participant is expected to receive a live vaccination at any time during the study.

4. Participant received the Bacillus Calmette-Guerin (BCG) vaccine within the past year.

5. Participant is expected to receive the BCG vaccine at any time during the study or up to one year after discontinuing ustekinumab.

6. Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years.

7. Participant has received intraocular (or periocular) steroid or anti-vascular endothelial growth factor (VEGF) injections within the last six weeks.

8. Participant received rituximab within the last six months or another biologic agent (e.g., infliximab, daclizumab, adalimumab) within the last two months.

9. Participant has received alkylating agents (e.g., cyclophosphamide, chlorambucil) within the last nine months.

10. Participant has a known hypersensitivity to ustekinumab or any of its components.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Eye Institute (NEI)

Investigators

• Principal Investigator: Hatice N Sen, M.D., National Eye Institute (NEI)

Study Documents (Full-Text)

• Study Protocol - Sep 18, 2019
• Statistical Analysis Plan - Nov 20, 2020

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: National Eye Institute (NEI)
• ClinicalTrials.gov Identifier: NCT02911116
• Other Study ID Numbers: 160169; 16-EI-0169
• First Posted: Sep 22, 2016
• Last Update Posted: Mar 26, 2021
• Last Verified: Dec 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Eye Institute (NEI): Panuveitis; Intermediate Uveitis; Uveitis
• Additional relevant MeSH terms: Uveitis; Ustekinumab

Study Results

Participant Flow

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Period Title: Overall Study
STARTED	5	3
COMPLETED	4	2
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)	Total
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion	Total of all reporting groups
Overall Participants	5	3	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	3 100%	8 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51 (9)	48 (9)	50 (9)
Sex: Female, Male (Count of Participants)
Female	2 40%	1 33.3%	3 37.5%
Male	3 60%	2 66.7%	5 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 20%	0 0%	1 12.5%
Not Hispanic or Latino	4 80%	3 100%	7 87.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 60%	0 0%	3 37.5%
White	1 20%	3 100%	4 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 20%	0 0%	1 12.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Experiencing a Treatment Response by Week 16
Description	The primary outcome is the number of participants in each cohort who experience a treatment response by Week 16. Treatment response is defined as experiencing all of the following for both/eligible eyes: no active inflammatory chorioretinal lesion and/or absent or decreased retinal vascular leakage; ≤ 0.5+ anterior chamber (AC) cells; ≤ 0.5+ vitreous haze.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Count of Participants [Participants]	4 80%	2 66.7%

2. Secondary Outcome

Title	Mean Change in Visual Acuity in the Right Eye at All Follow-up Visits Compared to Baseline
Description	Mean change in visual acuity in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline as measured by electronic visual acuity (EVA).
Time Frame	Baseline to Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16. At Week 28, one additional participant in Cohort 2 is excluded from the analysis due to missing visual acuity data.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Week 4	-1 (3)	-1 (1)
Week 8	1 (3)	1 (4)
Week 12	2 (4)	0 (3)
Week 16	1 (8)	0 (1)
Week 28	-2 (7)	-1 (NA)

3. Secondary Outcome

Title	Mean Change in Visual Acuity in the Left Eye at All Follow-up Visits Compared to Baseline
Description	Mean change in visual acuity in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline as measured by electronic visual acuity (EVA).
Time Frame	Baseline to Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16. At Week 28, one additional participant in Cohort 2 is excluded from the analysis due to missing visual acuity data.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Week 4	-2 (7)	1 (4)
Week 8	4 (5)	1 (2)
Week 12	4 (6)	1 (2)
Week 16	0 (13)	0 (0)
Week 28	6 (10)	-5 (NA)

4. Secondary Outcome

Title	Median Change in Visual Acuity in the Right Eye at All Follow-up Visits Compared to Baseline
Description	Median change in visual acuity in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline as measured by electronic visual acuity (EVA).
Time Frame	Baseline to Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16. At Week 28, one additional participant in Cohort 2 is excluded from the analysis due to missing visual acuity data.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Week 4	-1	-1
Week 8	2	1
Week 12	3	0
Week 16	4	0
Week 28	1	-1

5. Secondary Outcome

Title	Median Change in Visual Acuity in the Left Eye at All Follow-up Visits Compared to Baseline
Description	Median change in visual acuity in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline as measured by electronic visual acuity (EVA).
Time Frame	Baseline to Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16. At Week 28, one additional participant in Cohort 2 is excluded from the analysis due to missing visual acuity data.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Week 4	-2	1
Week 8	2	1
Week 12	3	1
Week 16	1	0
Week 28	3	-5

6. Secondary Outcome

Title	Number of Participants Who Experience a Recurrence of Uveitis at All Follow-up Visits
Description	Number of participants in each cohort who experience a recurrence of uveitis at each follow-up visit (Week 4, Week 8, Week 12, and Week 16). Recurrence of uveitis is defined as the presence of one of the following in at least one eye: 1) new active inflammatory chorioretinal lesion and/or retinal vascular leakage; 2) a 2+ increase in anterior chamber (AC) cells relative to Baseline; 3) a 2-step increase in vitreous haze (VH) relative to Baseline; 4) worsening of best-corrected visual acuity (BCVA) by ≥ 15 letters relative to Baseline.
Time Frame	Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Week 4	0 0%	0 0%
Week 8	0 0%	0 0%
Week 12	0 0%	0 0%
Week 16	1 20%	0 0%

7. Secondary Outcome

Title	Mean Number of Days Until First Recurrence
Description	Mean number of days following the baseline injection until first recurrence (of the participants who recur). Recurrence of uveitis is defined as the presence of one of the following in at least one eye: 1) new active inflammatory chorioretinal lesion and/or retinal vascular leakage; 2) a 2+ increase in anterior chamber (AC) cells relative to Baseline; 3) a 2-step increase in vitreous haze (VH) relative to Baseline; 4) worsening of best-corrected visual acuity (BCVA) by ≥ 15 letters relative to Baseline.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab, completed the Week 16 visit, and experienced recurrence of uveitis. As only one participant experienced recurrence of uveitis, only one participant from Cohort 1 is included in the analysis.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	1	0
Mean (Standard Deviation) [days]	118 (NA)

8. Secondary Outcome

Title	Median Number of Days Until First Recurrence
Description	Median number of days following the baseline injection until first recurrence (of the participants who recur). Recurrence of uveitis is defined as the presence of one of the following in at least one eye: 1) new active inflammatory chorioretinal lesion and/or retinal vascular leakage; 2) a 2+ increase in anterior chamber (AC) cells relative to Baseline; 3) a 2-step increase in vitreous haze (VH) relative to Baseline; 4) worsening of best-corrected visual acuity (BCVA) by ≥ 15 letters relative to Baseline.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab, completed the Week 16 visit, and experienced recurrence of uveitis. As only one participant experienced recurrence of uveitis, only one participant from Cohort 1 is included in the analysis.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	1	0
Median (Full Range) [days]	118

9. Secondary Outcome

Title	Presence or Extent of Macular Edema as Determined by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits
Description	Presence or extent of macular edema as determined by optical coherence tomography (OCT) in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants that did and did not have macular edema present is presented.
Time Frame	Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Present	2 40%	0 0%
Not Present	2 40%	2 66.7%
Present	2 40%	0 0%
Not Present	2 40%	2 66.7%
Present	1 20%	0 0%
Not Present	3 60%	2 66.7%
Present	1 20%	0 0%
Not Present	3 60%	2 66.7%
Present	3 60%	0 0%
Not Present	1 20%	2 66.7%

10. Secondary Outcome

Title	Presence or Extent of Macular Edema as Determined by Optical Coherence Tomography (OCT) in the Left Eye at All Follow-up Visits
Description	Presence or extent of macular edema as determined by optical coherence tomography (OCT) in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants that did and did not have macular edema present is presented.
Time Frame	Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Present	0 0%	0 0%
Not Present	3 60%	2 66.7%
Present	1 20%	0 0%
Not Present	3 60%	2 66.7%
Present	1 20%	0 0%
Not Present	3 60%	2 66.7%
Present	1 20%	0 0%
Not Present	3 60%	2 66.7%
Present	2 40%	0 0%
Not Present	2 40%	2 66.7%

11. Secondary Outcome

Title	Presence or Extent of Macular Edema as Determined by Fluorescein Angiogram (FA) in the Right Eye at All Follow-up Visits
Description	Presence or extent of macular edema as determined by fluorescein angiogram (FA) in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants that did and did not have macular edema present is presented.
Time Frame	Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16. No participants in Cohort 2 were analyzed at Week 4 as neither had FA performed at that visit.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Present	2 40%
Not Present	0 0%
Present	4 80%	0 0%
Not Present	0 0%	2 66.7%
Present	3 60%	0 0%
Not Present	0 0%	2 66.7%
Present	3 60%	0 0%
Not Present	1 20%	2 66.7%
Present	3 60%	1 33.3%
Not Present	1 20%	1 33.3%

12. Secondary Outcome

Title	Presence or Extent of Macular Edema as Determined by Fluorescein Angiogram (FA) in the Left Eye at All Follow-up Visits
Description	Presence or extent of macular edema as determined by fluorescein angiogram (FA) in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants that did and did not have macular edema present is presented.
Time Frame	Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16. No participants in Cohort 2 were analyzed at Week 4 as neither had FA performed at that visit.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Present	1 20%
Not Present	1 20%
Present	2 40%	0 0%
Not Present	2 40%	2 66.7%
Present	3 60%	0 0%
Not Present	0 0%	2 66.7%
Present	3 60%	1 33.3%
Not Present	1 20%	1 33.3%
Present	4 80%	2 66.7%
Not Present	0 0%	0 0%

13. Secondary Outcome

Title	Amount of Retino-vascular Leakage as Measured by Fluorescein Angiogram (FA) in the Right Eye at All Follow-up Visits
Description	Amount of retino-vascular leakage as measured by fluorescein angiogram (FA) in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28). The number of participants experiencing presence and new/increased lesions, presence and decreased lesions, presence and no new/increased or decreased lesions, and absence of lesions are presented.
Time Frame	Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Presence and New/Increased Lesions	0 0%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	1 20%	0 0%
Absence of Lesions	3 60%	2 66.7%
Presence and New/Increased Lesions	0 0%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	0 0%	1 33.3%
Absence of Lesions	4 80%	1 33.3%
Presence and New/Increased Lesions	0 0%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	0 0%	2 66.7%
Absence of Lesions	4 80%	0 0%
Presence and New/Increased Lesions	1 20%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	0 0%	1 33.3%
Absence of Lesions	3 60%	1 33.3%
Presence and New/Increased Lesions	0 0%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	0 0%	0 0%
Absence of Lesions	4 80%	2 66.7%

14. Secondary Outcome

Title	Amount of Retino-vascular Leakage as Measured by Fluorescein Angiogram (FA) in the Left Eye at All Follow-up Visits
Description	Amount of retino-vascular leakage as measured by fluorescein angiogram (FA) in the left eye at all follow-up visits (Week 4, week 8, Week 12, Week 16, and Week 28). The number of participants experiencing presence and new/increased lesions, presence and decreased lesions, presence and no new/increased or decreased lesions, and absence of lesions are presented.
Time Frame	Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Presence and New/Increased Lesions	0 0%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	1 20%	0 0%
Absence of Lesions	3 60%	2 66.7%
Presence and New/Increased Lesions	0 0%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	0 0%	0 0%
Absence of Lesions	4 80%	2 66.7%
Presence and New/Increased Lesions	0 0%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	0 0%	1 33.3%
Absence of Lesions	4 80%	1 33.3%
Presence and New/Increased Lesions	1 20%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	0 0%	0 0%
Absence of Lesions	3 60%	2 66.7%
Presence and New/Increased Lesions	0 0%	0 0%
Presence and Decreased Lesions	0 0%	0 0%
Presence and No New/Increased or Decreased Lesions	0 0%	0 0%
Absence of Lesions	4 80%	2 66.7%

15. Secondary Outcome

Title	Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits Compared to Baseline
Description	Mean change in central retinal thickness as measured by optical coherence tomography (OCT) in the right eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline.
Time Frame	Baseline to Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Week 4	8 (14)	-2 (4)
Week 8	-49 (95)	-6 (12)
Week 12	-11 (13)	6 (1)
Week 16	-28 (16)	-7 (16)
Week 28	-9 (40)	-2 (11)

16. Secondary Outcome

Title	Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Left Eye at All Follow-up Visits Compared to Baseline
Description	Mean change in central retinal thickness as measured by optical coherence tomography (OCT) in the left eye at all follow-up visits (Week 4, Week 8, Week 12, Week 16, and Week 28) compared to baseline.
Time Frame	Baseline to Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Week 4	-13 (26)	1 (1)
Week 8	17 (34)	-1 (6)
Week 12	54 (87)	2 (4)
Week 16	-2 (31)	8 (6)
Week 28	-1 (24)	19 (6)

17. Secondary Outcome

Title	Length of Time to Quiescence in the Right Eye
Description	Mean length of time to first experience of quiescence in the right eye. Quiescence refers to absence of active disease defined as not having the following conditions: +1 or more vitreous haze; and/or active chorioretinitis or leakage on fluorescein angiogram (FA) (that is more than one quadrant) that requires treatment.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab, completed the Week 16 visit, and experienced quiescence. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16. An additional participant in Cohort 1 is excluded due to not experiencing quiescence.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	3	2
Mean (Standard Deviation) [days]	24 (8)	38 (8)

18. Secondary Outcome

Title	Length of Time to Quiescence in the Left Eye
Description	Mean length of time to first experience of quiescence in the left eye. Quiescence refers to absence of active disease defined as not having the following conditions: +1 or more vitreous haze; and/or active chorioretinitis or leakage on fluorescein angiogram (FA) (that is more than one quadrant) that requires treatment.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab, completed the Week 16 visit, and experienced quiescence. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16. An additional participant in Cohort 1 is excluded due to not experiencing quiescence.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	3	2
Mean (Standard Deviation) [days]	38 (16)	38 (8)

19. Secondary Outcome

Title	Ability to Taper Concomitant Immunosuppressive Medications
Description	The number of participants able to taper concomitant immunosuppressive medications.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in Cohort 1 is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Count of Participants [Participants]	1 20%	0 0%

20. Other Pre-specified Outcome

Title	Number of Participants Experiencing a Clinically Significant Increase in Elevated Intraocular Pressure (IOP) at Any Follow-up Visit
Description	Number of participants experiencing a clinically significant increase in elevated intraocular pressure (IOP) at any follow-up visit in either eye. An increase in IOP ≥10 mmHg as compared with baseline is considered a clinically significant increase.
Time Frame	Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Count of Participants [Participants]	2 40%	0 0%

21. Other Pre-specified Outcome

Title	Proportion of Participants With ≥15 Letter Loss at Any Follow-up Visit.
Description	Proportion of participants with ≥15 letter loss in best-corrected visual acuity (BCVA) from baseline at any follow-up visit in either eye.
Time Frame	Week 4, Week 8, Week 12, Week 16, Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Count of Participants [Participants]	1 20%	0 0%

22. Other Pre-specified Outcome

Title	Number and Severity of Systemic and Ocular Toxicities and Adverse Events
Description	Number and severity of systemic and ocular toxicities and adverse events for participants in both cohorts. Severity of each event is classified as mild, moderate, or severe. Natural progression of disease adverse events are not included.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of Ustekinumab and completed the Week 16 visit. One participant in each cohort is excluded from the analysis as a result of discontinuing the study prior to Week 16.

Arm/Group Title	Cohort 1 (Subcutaneous Only)	Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection	Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
Measure Participants	4	2
Mild	10	7
Moderate	3	3
Severe	0	0

Adverse Events

Time Frame	28 weeks
Arm/Group Title	Cohort 1 (Subcutaneous Only)		Cohort 2 (IV and Subcutaneous)
Arm/Group Description	Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection		Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion
All Cause Mortality
	Cohort 1 (Subcutaneous Only)		Cohort 2 (IV and Subcutaneous)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/3 (0%)
Serious Adverse Events
	Cohort 1 (Subcutaneous Only)		Cohort 2 (IV and Subcutaneous)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 (Subcutaneous Only)		Cohort 2 (IV and Subcutaneous)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		3/3 (100%)
Cardiac disorders
Tachycardia	1/5 (20%)	1	0/3 (0%)	0
Eye disorders
conjunctivitis allergic	0/5 (0%)	0	1/3 (33.3%)	1
Keratitis	1/5 (20%)	1	0/3 (0%)	0
Visual acuity reduced	2/5 (40%)	2	0/3 (0%)	0
Vitreous floaters	1/5 (20%)	1	0/3 (0%)	0
Ocular hyperaemia	1/5 (20%)	1	0/3 (0%)	0
Subretinal fluid	1/5 (20%)	1	0/3 (0%)	0
Cystoid macular oedema	1/5 (20%)	2	0/3 (0%)	0
Iris adhesions	1/5 (20%)	1	0/3 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/5 (20%)	1	0/3 (0%)	0
Dyspepsia	1/5 (20%)	1	0/3 (0%)	0
General disorders
Adverse drug reaction	0/5 (0%)	0	1/3 (33.3%)	1
Fatigue	0/5 (0%)	0	1/3 (33.3%)	1
Pyrexia	0/5 (0%)	0	1/3 (33.3%)	1
Infections and infestations
Upper respiratory tract infection	2/5 (40%)	2	0/3 (0%)	0
Urinary tract infection	0/5 (0%)	0	1/3 (33.3%)	1
Injury, poisoning and procedural complications
Fall	1/5 (20%)	1	0/3 (0%)	0
Upper limb fracture	1/5 (20%)	1	0/3 (0%)	0
Investigations
Blood pressure increased	1/5 (20%)	1	0/3 (0%)	0
Neutrophil count decreased	1/5 (20%)	1	0/3 (0%)	0
Vitamin D decreased	1/5 (20%)	1	0/3 (0%)	0
White blood cell count decreased	1/5 (20%)	1	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/5 (0%)	0	2/3 (66.7%)	2
Nervous system disorders
Neuropathy peripheral	0/5 (0%)	0	1/3 (33.3%)	1
Paraesthesia	0/5 (0%)	0	1/3 (33.3%)	1
Psychiatric disorders
Depression	0/5 (0%)	0	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders
Acne	1/5 (20%)	1	0/3 (0%)	0
Surgical and medical procedures
Polypectomy	0/5 (0%)	0	1/3 (33.3%)	1
Vascular disorders
Phlebitis	0/5 (0%)	0	1/3 (33.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.