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| ID | Type | Description | Link |
|---|---|---|---|
| 16-EI-0169 |
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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:
Participants will have their uveitis monitored and receive standard uveitis care during the study.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (Subcutaneous Only) | Experimental | Subcutaneous injections of Ustekinumab at baseline. |
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| Cohort 2 (IV and Subcutaneous) | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ustekinumab | Drug | Subcutaneous Injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing a Treatment Response by 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. | Baseline to Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change in Visual Acuity in the Right Eye at All Follow-up Visits Compared to Baseline | 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). | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing a Clinically Significant Increase in Elevated Intraocular Pressure (IOP) at Any Follow-up Visit | 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. | Week 4, Week 8, Week 12, Week 16, Week 28 |
-INCLUSION CRITERIA:
Participant has the ability to understand and sign the informed consent document.
Participant is 18 years of age or older.
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.
Participant has active intermediate uveitis, posterior uveitis or panuveitis in at least one eye requiring systemic therapy. Active disease is defined as:
Participant has visual acuity in at least one eye of 20/400 or better.
Participant is willing and able to comply with the study procedures.
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.
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:
EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| Hatice N Sen, M.D. | National Eye Institute (NEI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892 | United States |
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| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 (Subcutaneous Only) | Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection |
| FG001 | 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. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 (Subcutaneous Only) | Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection |
| BG001 | 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. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Experiencing a Treatment Response by 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. | 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. | Posted | Count of Participants | Participants | Baseline to Week 16 |
|
28 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 (Subcutaneous Only) | Subcutaneous injections of Ustekinumab at baseline. Ustekinumab: Subcutaneous Injection |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| H. Nida Sen, MD, MHSc, Principal Investigator, NEI | National Institutes of Health | 301-402-3254 | senh@nei.nih.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 18, 2019 | Feb 5, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 20, 2020 | Feb 5, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D014605 | Uveitis |
| D015864 | Panuveitis |
| D015867 | Uveitis, Intermediate |
| ID | Term |
|---|---|
| D014603 | Uveal Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| D000069549 | Ustekinumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Ustekinumab | Drug | Intravenous Infusion |
|
| Mean Change in Visual Acuity in the Left Eye at All Follow-up Visits Compared to Baseline |
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). |
| 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 Compared to Baseline | 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). | 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 Compared to Baseline | 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). | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
| Number of Participants Who Experience a Recurrence of Uveitis at All Follow-up Visits | 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. | Week 4, Week 8, Week 12, Week 16 |
| Mean Number of Days Until First Recurrence | 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. | Baseline to Week 16 |
| Median Number of Days Until First Recurrence | 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. | Baseline to Week 16 |
| Presence or Extent of Macular Edema as Determined by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits | 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. | 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 | 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. | 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 | 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. | 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 | 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. | 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 | 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. | 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 | 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. | Week 4, Week 8, Week 12, Week 16, Week 28 |
| Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits Compared to Baseline | 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. | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
| Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Left Eye at All Follow-up Visits Compared to Baseline | 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. | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
| Length of Time to Quiescence in the Right Eye | 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. | Baseline to Week 16 |
| Length of Time to Quiescence in the Left Eye | 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. | Baseline to Week 16 |
| Ability to Taper Concomitant Immunosuppressive Medications | The number of participants able to taper concomitant immunosuppressive medications. | Baseline to Week 28 |
| Proportion of Participants With ≥15 Letter Loss at Any Follow-up Visit. | Proportion of participants with ≥15 letter loss in best-corrected visual acuity (BCVA) from baseline at any follow-up visit in either eye. | Week 4, Week 8, Week 12, Week 16, Week 28 |
| Number and Severity of Systemic and Ocular Toxicities and Adverse Events | 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. | Baseline to Week 28 |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| OG001 | 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. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion |
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| Secondary | Mean Change in Visual Acuity in the Right Eye at All Follow-up Visits Compared to Baseline | 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). | 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. | Posted | Mean | Standard Deviation | letters read | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Mean Change in Visual Acuity in the Left Eye at All Follow-up Visits Compared to Baseline | 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). | 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. | Posted | Mean | Standard Deviation | letters read | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Median Change in Visual Acuity in the Right Eye at All Follow-up Visits Compared to Baseline | 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). | 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. | Posted | Median | Full Range | letters read | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Median Change in Visual Acuity in the Left Eye at All Follow-up Visits Compared to Baseline | 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). | 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. | Posted | Median | Full Range | letters read | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Number of Participants Who Experience a Recurrence of Uveitis at All Follow-up Visits | 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. | 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. | Posted | Count of Participants | Participants | Week 4, Week 8, Week 12, Week 16 |
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| Secondary | Mean Number of Days Until First Recurrence | 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. | 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. | Posted | Mean | Standard Deviation | days | Baseline to Week 16 |
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| Secondary | Median Number of Days Until First Recurrence | 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. | 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. | Posted | Median | Full Range | days | Baseline to Week 16 |
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| Secondary | Presence or Extent of Macular Edema as Determined by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits | 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. | 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. | Posted | Count of Participants | Participants | Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Presence or Extent of Macular Edema as Determined by Optical Coherence Tomography (OCT) in the Left Eye at All Follow-up Visits | 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. | 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. | Posted | Count of Participants | Participants | Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Presence or Extent of Macular Edema as Determined by Fluorescein Angiogram (FA) in the Right Eye at All Follow-up Visits | 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. | 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. | Posted | Count of Participants | Participants | Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Presence or Extent of Macular Edema as Determined by Fluorescein Angiogram (FA) in the Left Eye at All Follow-up Visits | 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. | 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. | Posted | Count of Participants | Participants | Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Amount of Retino-vascular Leakage as Measured by Fluorescein Angiogram (FA) in the Right Eye at All Follow-up Visits | 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. | 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. | Posted | Count of Participants | Participants | Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Amount of Retino-vascular Leakage as Measured by Fluorescein Angiogram (FA) in the Left Eye at All Follow-up Visits | 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. | 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. | Posted | Count of Participants | Participants | Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits Compared to Baseline | 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. | 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. | Posted | Mean | Standard Deviation | micrometers | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Left Eye at All Follow-up Visits Compared to Baseline | 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. | 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. | Posted | Mean | Standard Deviation | micrometers | Baseline to Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Secondary | Length of Time to Quiescence in the Right Eye | 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. | 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. | Posted | Mean | Standard Deviation | days | Baseline to Week 16 |
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| Secondary | Length of Time to Quiescence in the Left Eye | 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. | 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. | Posted | Mean | Standard Deviation | days | Baseline to Week 16 |
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| Secondary | Ability to Taper Concomitant Immunosuppressive Medications | The number of participants able to taper concomitant immunosuppressive medications. | 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. | Posted | Count of Participants | Participants | Baseline to Week 28 |
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| Other Pre-specified | Number of Participants Experiencing a Clinically Significant Increase in Elevated Intraocular Pressure (IOP) at Any Follow-up Visit | 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. | 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. | Posted | Count of Participants | Participants | Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Other Pre-specified | Proportion of Participants With ≥15 Letter Loss at Any Follow-up Visit. | Proportion of participants with ≥15 letter loss in best-corrected visual acuity (BCVA) from baseline at any follow-up visit in either eye. | 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. | Posted | Count of Participants | Participants | Week 4, Week 8, Week 12, Week 16, Week 28 |
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| Other Pre-specified | Number and Severity of Systemic and Ocular Toxicities and Adverse Events | 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. | 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. | Posted | Number | adverse events | Baseline to Week 28 |
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|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 4 |
| 5 |
| EG001 | 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. Ustekinumab: Subcutaneous Injection Ustekinumab: Intravenous Infusion | 0 | 3 | 0 | 3 | 3 | 3 |
| conjunctivitis allergic | Eye disorders | MedDRA 22.1 | Systematic Assessment |
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| Keratitis | Eye disorders | MedDRA 22.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Adverse drug reaction | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Vitamin D decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Neuropathy peripheral | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Polypectomy | Surgical and medical procedures | MedDRA 23.0 | Systematic Assessment |
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| Phlebitis | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Visual acuity reduced | Eye disorders | MedDRA 22.0 | Systematic Assessment | Natural progression of disease event |
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| Vitreous floaters | Eye disorders | MedDRA 22.0 | Systematic Assessment | Natural progression of disease event |
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| Ocular hyperaemia | Eye disorders | MedDRA 22.0 | Systematic Assessment | Natural progression of disease event |
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| Subretinal fluid | Eye disorders | MedDRA 22.0 | Systematic Assessment | Natural progression of disease event |
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| Cystoid macular oedema | Eye disorders | MedDRA 22.0 | Systematic Assessment | Natural progression of disease event |
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| Iris adhesions | Eye disorders | MedDRA 22.0 | Systematic Assessment | Natural progression of disease event |
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Not provided
Not provided
Not provided
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Week 12 |
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| Week 16 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Not Present |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Not Present |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Not Present |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Presence and No New/Increased or Decreased Lesions |
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| Absence of Lesions |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Presence and No New/Increased or Decreased Lesions |
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| Absence of Lesions |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Week 12 |
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| Week 16 |
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| Week 28 |
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| Severe |
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