Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis (STAR Study)
| Status: | Recruiting |
|---|---|
| Conditions: | Cervical Cancer, Ocular |
| Therapuetic Areas: | Oncology, Ophthalmology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/10/2019 |
| Start Date: | September 21, 2016 |
| End Date: | July 18, 2019 |
| Contact: | Dominic Obiyor, R.N. |
| Email: | dobiyor@mail.nih.gov |
| Phone: | (301) 435-4556 |
A Pilot Study to Investigate Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis
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.
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.
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. 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).
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. 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).
-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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
Phone: 800-411-1222
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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