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

ID: NCT02911116
Status: Recruiting
Phase: Phase 2
Start Date: September 21, 2016
First Submitted: September 21, 2016
Last Updated: February 22, 2018
Results: N/A
Sponsors & Collaborators: National Eye Institute (NEI)
Location: United States
Conditions: Uveitis
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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.

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.

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 subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis.

Study Population: Five participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria will be initially enrolled. Up to seven participants may be enrolled, as up to two participants may be accrued to account for participants who withdraw from the study prior to Week 16.

Design: This is a prospective, non-randomized, uncontrolled, single-center pilot study to evaluate subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis. Participants will receive a 90 mg subcutaneous injection of ustekinumab at baseline and a second and third injection at Week 4 and 8 for a total of 3 injections. 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: The primary outcome is the number of participants who experience treatment response by Week 16. Secondary outcomes 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 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).
Condition or disease Intervention/treatment Phase

Uveitis

Drug: Ustekinumab
Other Names
Phase 2

Tracking Information

First Submitted DateSeptember 21, 2016
Last Update Posted DateFebruary 22, 2018
Start DateSeptember 21, 2016
Anticipated Completion DateDecember 31, 2018
Primary Completion DateDecember 31, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • The primary outcome is the number of participants who experience a treatment response by Week. [Time Frame: 16 Weeks]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Mean and median change in visual acuity. [Time Frame: Ongoing]

  • Presence or extent of macular edema as determined by OCT and FA at all follow-up visits. [Time Frame: Ongoing]

  • Amount of retino-vascular leakage as measured by FA at all follow-up visits. [Time Frame: Ongoing]

  • Mean and median number of days following the baseline injection until first recurrence (of the participants who recur). [Time Frame: Ongoing]

  • Number of participants who experience a recurrence. [Time Frame: Ongoing]

  • Changes in retinal thickening as measured by OCT at all follow-up visits. [Time Frame: Ongoing]

  • Length of time to quiescence. [Time Frame: Ongoing]

  • Ability to taper concomitant immunosuppressive medications. [Time Frame: Ongoing]

  • Number and severity of systemic and ocular toxicities and adverse events. [Time Frame: Ongoing]

  • Proportion of participants with loss of greater than or equal to 15 letters at any follow-up visit. [Time Frame: Ongoing]

  • Number of participants experiencing a clinically significant increase in elevated IOP at any follow-up visit. A change of greater than or equal to 10 mmHg as compared with baseline is considered a clinically significant increase. [Time Frame: Ongoing]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleUstekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis (STAR Study)
Official TitleA Pilot Study to Investigate Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis
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.

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.

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 subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis.

Study Population: Five participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria will be initially enrolled. Up to seven participants may be enrolled, as up to two participants may be accrued to account for participants who withdraw from the study prior to Week 16.

Design: This is a prospective, non-randomized, uncontrolled, single-center pilot study to evaluate subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis. Participants will receive a 90 mg subcutaneous injection of ustekinumab at baseline and a second and third injection at Week 4 and 8 for a total of 3 injections. 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: The primary outcome is the number of participants who experience treatment response by Week 16. Secondary outcomes 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 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 TypeInterventional
Study PhasePhase 2
Estimated Enrollment
7
Allocation
Not Available
Interventional Model
Single Group Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Uveitis
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Ustekinumab

Other Names
Study Groups/Cohorts
Ustekinumab
Subcutaneous injections of ustekinumab

Study Arms
Experimental Ustekinumab
Subcutaneous injections of ustekinumab
Drug : Ustekinumab

Arm Intervention/Treatment
Experimental Ustekinumab
Subcutaneous injections of ustekinumab
Drug : Ustekinumab

Recruitment Information

Recruitment Status:Recruiting
Enrollment7
Completion DateDecember 31, 2018
Eligibility Criteria: -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.
5. Participant has visual acuity in at least one eye of 20/400 or better.
6. Participant is willing and able to comply with the study procedures.
7. 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.
8. 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-Gu(SqrRoot)(Copyright)rin (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.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT02911116
Other Study ID Numbers
160169
16-EI-0169
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
National Eye Institute (NEI)
Collaborators
Not Available
Investigators
Principal Investigator
Hatice N Sen, M.D.
National Eye Institute (NEI)