UveitisPhase 2SAVE-2NCT01280669
Intravitreal Sirolimus as Therapeutic Approach to Uveitis
A Phase 2 study testing Intravitreal injection 440mcg and Intravitreal injection of sirolimus 880mcg in people with Uveitis and Intermediate Uveitis, run by Stanford University at 1 site in United States.
Trial summary
The purpose of this study is to find out about the safety and effectiveness of two different doses the study drug, sirolimus, administered intravitreally in patients with uveitis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveitis, Intermediate Uveitis, Posterior Uveitis
- What is being tested?
- Intravitreal injection 440mcg and Intravitreal injection of sirolimus 880mcg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2022to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females greater than or equal to 12 years of age.
- Able to give informed consent and attend all study visits.
- Have diagnosis of uveitis determined by the Investigator to be non-infectious based on the patient's medical history, history of present illness, ocular examination, review of systems, physical examination, and any pertinent laboratory evaluations.
- Meet the following criteria:
- Have active uveitis, defined as having at least 1+ Vitreous Haze and/or at least 1+ Vitreous Cell Count (SUN scale), and:
- are receiving no treatment; or
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- are receiving:
- prednisone ≥ 10 mg/day (or equivalent dose of another corticosteroid), or
- at least 1 systemic immunosuppressant other than corticosteroids, or
- combination of prednisone ≥ 10 mg/day (or equivalent dose of another corticosteroid) and other systemic immunosuppressant.
- Have inactive disease, defined as having 0.5+ Vitreous Haze or less and 0.5+ or less Vitreous Cell Count (SUN scale), and:
- are receiving:
- prednisone <10 mg/day (or equivalent dose of another corticosteroid), or
- at least 1 systemic immunosuppressant other than corticosteroids, or
- combination of prednisone <10 mg/day (or equivalent dose of another corticosteroid) and other systemic immunosuppressant.
- Have posterior, intermediate, or panuveitis; for panuveitis, if an anterior component is present, it must be less than the posterior component.
- Sufficient inflammation to require systemic treatment and, based on the Investigator's decision, warrants intravitreal treatment.
- Best-corrected ETDRS visual acuity of 20/400 or better (approximately 20 letters) in the study eye.
- Best-corrected ETDRS visual acuity of 20/400 or better in the fellow eye (approximately 20 letters).
Who cannot join
- Patients with bilateral uveitis who are receiving systemic immunosuppressive therapy (e.g., methotrexate, cyclosporine, cyclophosphamide, chlorambucil, mycophenolate mofetil, tacrolimus, or azathioprine) other than prednisone or other corticosteroids for the treatment of uveitis and the uveitis in the fellow eye, in the opinion of the Investigator, cannot be controlled with standard local therapies alone;
- Any significant ocular disease that could compromise the visual outcome in the study eye.
- Intravitreal injections (including but not limited to anti-vascular endothelial growth factors 60 days prior to the baseline;
- Posterior subtenon's or intravitreal injection of steroids 90 days prior to Baseline;
- Intraocular surgery within 90 days prior to Day 0 in the study eye;
- Capsulotomy within 30 days prior to Day 0 in the study eye;
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- History of vitreoretinal surgery or scleral buckling within 90 days prior to Day 0 in the study eye;
- Any ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated within the first 180 days following Day 0;
- Intraocular pressure ≥25 mmHg in the study eye (glaucoma patients maintained on no more than 2 topical medications with IOP <25 mmHg are allowed to participate);
- Pupillary dilation inadequate for quality fundus photography in the study eye;
- Media opacity that would limit clinical visualization, intravenous fluorescein angiography (IVFA), or OCT evaluation in the study eye;
- Presence of any form of ocular malignancy in the study eye, including choroidal melanoma;
- History of herpetic infection in the study eye or adnexa;
- Presence of known active or inactive toxoplasmosis in either eye;
- Ocular or periocular infection in either eye;
- Participation in other investigational drug or device clinical trials within 30 days prior to Day 0, or planning to participate in other investigational drug or device clinical trials within 180 days following Day 0. This includes both ocular and non-ocular clinical trials.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sirolimus as a Therapeutic Approach for Uveitis: A Phase 2, Open-label, Randomized Study to Assess the Safety, Tolerability, and Bioactivity of Two Doses of Intravitreal Injection of Sirolimus in Patients With Non-infectious Uveitis
The purpose of this study is to find out about the safety and effectiveness of two different doses the study drug, sirolimus, administered intravitreally in patients with uveitis. The potential effectiveness of sirolimus can be utilized to control inflammation in uveitis and yet avoid the potential complications that are usually associated with the systemic use of the drug and other immunomodulatory therapies. In this study, the investigators will administer sirolimus inside the eye (intravitreally) in one of two doses (440mcg/mcL or 880mcg/mcL). Local administration of sirolimus to the eye is not expected to have effects on the rest of the body. Therefore, it may offer a safer way than the current methods used to control the inflammation caused by non-infectious uveitis.
Read the detailed description
Uveitis is a condition in which certain parts of your eye become inflamed. The inflammation is usually recurrent. If the inflammation is not treated adequately, permanent damage to the eye and to the vision may occur. The inflammation can be caused by infectious or non infectious causes. The current research is being done to determine the safety and the usefulness of treatment of non-infectious uveitis using different doses of intravitreal injections of a drug called sirolimus.
Current treatment options for uveitis include oral corticosteroids and drugs that weaken the immune system of the body (i.e., immunosuppressant drugs). Treatment using oral corticosteroids, especially for long periods, may cause many undesirable side effects and complications such as high blood sugar, high blood pressure, bone weakness, obesity, stomach ulcers, abnormal hair growth, and increased risks of infection. In addition to that, in some cases, the disease cannot be controlled even with the highest dose of steroids.
Injection of steroids around and inside the eye can be used to control uveitis. However, the inflammation does not always respond to such kind of treatment. The eyes may develop high pressure and cataract with injections of steroids into the eyes or around the eyes.
On the other hand, despite their potential effectiveness, treatment with drugs that weaken the immune system may cause severe side effects. Increased risk of infection is a common side effect of all the immunosuppressant drugs. The immune system protects the body from infections. When the immune system is suppressed, infections are more likely to happen. Some of these infections are potentially dangerous. Because the immune system protects the body against some forms of cancer, immunosuppressant drugs are also associated with a slightly increased risk of cancer. For example, long-term use of immunosuppressant drugs may carry an increased risk of developing skin cancer as a result of the combination of the drugs and exposure to sunlight. The immunosuppressive drugs are very powerful and can cause serious side effects such as high blood pressure, kidney problems, and liver problems. Some side effects may not show up until years after the medicine is used.
- Conditions
- Uveitis, Intermediate Uveitis, Posterior Uveitis, Panuveitis
- Being tested
- Intravitreal injection 440mcg, Intravitreal injection of sirolimus 880mcg
- Keywords
- Non-infectious, Uveitis, Panuveitis
- Medical subject headings
- Uveitis, Uveitis, Intermediate, Uveitis, Posterior, Panuveitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravitreal injection 440mcgDrug
Also called Low-dose, Monthly
Intravitreal injections of sirolimus 440mcg/20mcL at baseline and months 1, 2, 3, 4, and 5.
Intravitreal injection of sirolimus 880mcgDrug
Also called High-dose, Bi-monthly
Intravitreal injection of 880mcg/20mcL sirolimus at baseline and months 2 and 4.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Intravitreal injections of 440mcg sirolimus (low-dose monthly group) Receives: Drug: Intravitreal injection 440mcg |
| Group 2 | Experimental | Intravitreal injections of 880mcg sirolimus (high-dose every other month group) Receives: Drug: Intravitreal injection of sirolimus 880mcg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of uveitic attacks as assessed by vitreous haze and cells.
Measured: 6 months
Secondary outcomes (3)
Incidence of adverse and serious adverse events
Incidence, frequencey, and severity of adverse events reported during the first 6 months of the study period.
Measured: 6 months
Changes in central retinal thickness
Improvement or worsening of macular edema compared to baseline. Development of macular edema in patients with otherwise normal macualr thickness at baseline
Measured: 6 months
Steroid sparing effect
Proportion of subjects with active uveitis who achieve complete or partial response to sirolimus at month 6 while discontinuing their steroid therapy.
Proportion of subjects with inactive uveitis who maintain quiscent study eyes at month 6 while discontinuing their steroid therapy.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2011 (estimated)
- Study startSep 2022 (estimated)
- Primary completionSep 2024 (estimated)
- Study completionDec 2024 (estimated)
Why it stopped: Never started due to sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for UveitisStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Santen Inc.
- Responsible party
- Principal investigator, Quan Dong Nguyen, Stanford University
- Investigators
- Quan D Nguyen, MD, MSc, Principal investigator, Stanford University Byers Eye Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01280669
- Sponsor's protocol ID
- NA_00046190
- Acronym
- SAVE-2
- Status last verified
- Oct 2023
- First submitted
- 20 Jan 2011
- Last updated
- 26 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Teabagy S, Wood E, Bilsbury E, Doherty S, Janardhana P, Lee DJ. Ocular immunosuppressive microenvironment and novel drug delivery for control of uveitis. Adv Drug Deliv Rev. 2023 Jul;198:114869. doi: 10.1016/j.addr.2023.114869. Epub 2023 May 10.
PubMed 37172782
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sirolimus as a Therapeutic Approach for Uveitis: A Phase 2, Open-label, Randomized Study to Assess the Safety, Tolerability, and Bioactivity of Two Doses of Intravitreal Injection of Sirolimus in Patients With Non-infectious Uveitis
- ClinicalTrials.gov ID
- NCT01280669
- Acronym / sponsor ID
- SAVE-2 / NA_00046190
- Conditions
- Uveitis, Intermediate Uveitis, Posterior Uveitis, Panuveitis
- Keywords
- Non-infectious, Uveitis, Panuveitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Never started due to sponsor decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Santen Inc.
- Study start
- Sep 2022 (estimated)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 21 Jan 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out about the safety and effectiveness of two different doses the study drug, sirolimus, administered intravitreally in patients with uveitis. The potential effectiveness of sirolimus can be utilized to control inflammation in uveitis and yet avoid the potential complications that are usually associated with the systemic use of the drug and other immunomodulatory therapies. In this study, the investigators will administer sirolimus inside the eye (intravitreally) in one of two doses (440mcg/mcL or 880mcg/mcL). Local administration of sirolimus to the eye is not expected to have effects on the rest of the body. Therefore, it may offer a safer way than the current methods used to control the inflammation caused by non-infectious uveitis.
Detailed description
Uveitis is a condition in which certain parts of your eye become inflamed. The inflammation is usually recurrent. If the inflammation is not treated adequately, permanent damage to the eye and to the vision may occur. The inflammation can be caused by infectious or non infectious causes. The current research is being done to determine the safety and the usefulness of treatment of non-infectious uveitis using different doses of intravitreal injections of a drug called sirolimus.
Current treatment options for uveitis include oral corticosteroids and drugs that weaken the immune system of the body (i.e., immunosuppressant drugs). Treatment using oral corticosteroids, especially for long periods, may cause many undesirable side effects and complications such as high blood sugar, high blood pressure, bone weakness, obesity, stomach ulcers, abnormal hair growth, and increased risks of infection. In addition to that, in some cases, the disease cannot be controlled even with the highest dose of steroids.
Injection of steroids around and inside the eye can be used to control uveitis. However, the inflammation does not always respond to such kind of treatment. The eyes may develop high pressure and cataract with injections of steroids into the eyes or around the eyes.
On the other hand, despite their potential effectiveness, treatment with drugs that weaken the immune system may cause severe side effects. Increased risk of infection is a common side effect of all the immunosuppressant drugs. The immune system protects the body from infections. When the immune system is suppressed, infections are more likely to happen. Some of these infections are potentially dangerous. Because the immune system protects the body against some forms of cancer, immunosuppressant drugs are also associated with a slightly increased risk of cancer. For example, long-term use of immunosuppressant drugs may carry an increased risk of developing skin cancer as a result of the combination of the drugs and exposure to sunlight. The immunosuppressive drugs are very powerful and can cause serious side effects such as high blood pressure, kidney problems, and liver problems. Some side effects may not show up until years after the medicine is used.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Intravitreal injection 440mcgIntravitreal injections of 440mcg sirolimus (low-dose monthly group) |
| Group 2 | Experimental | Drug: Intravitreal injection of sirolimus 880mcgIntravitreal injections of 880mcg sirolimus (high-dose every other month group) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Males and females greater than or equal to 12 years of age.
- Able to give informed consent and attend all study visits.
- Have diagnosis of uveitis determined by the Investigator to be non-infectious based on the patient's medical history, history of present illness, ocular examination, review of systems, physical examination, and any pertinent laboratory evaluations.
- Meet the following criteria:
Key exclusion criteria (16 listed)
- Patients with bilateral uveitis who are receiving systemic immunosuppressive therapy (e.g., methotrexate, cyclosporine, cyclophosphamide, chlorambucil, mycophenolate mofetil, tacrolimus, or azathioprine) other than prednisone or other corticosteroids for the treatment of uveitis and the uveitis in the fellow eye, in the opinion of the Investigator, cannot be controlled with standard local therapies alone;
- Any significant ocular disease that could compromise the visual outcome in the study eye.
- Intravitreal injections (including but not limited to anti-vascular endothelial growth factors 60 days prior to the baseline;
- Posterior subtenon's or intravitreal injection of steroids 90 days prior to Baseline;
- Intraocular surgery within 90 days prior to Day 0 in the study eye;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravitreal injection 440mcgAlso: Low-dose, MonthlyIntravitreal injections of sirolimus 440mcg/20mcL at baseline and months 1, 2, 3, 4, and 5. | Drug | Group 1 |
| Intravitreal injection of sirolimus 880mcgAlso: High-dose, Bi-monthlyIntravitreal injection of 880mcg/20mcL sirolimus at baseline and months 2 and 4. | Drug | Group 2 |
Primary outcome
Frequency of uveitic attacks as assessed by vitreous haze and cells.
Time frame: 6 months
3 secondary outcomes
Incidence of adverse and serious adverse events
Time frame: 6 months
Changes in central retinal thickness
Time frame: 6 months
Steroid sparing effect
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2023.
- Derived from this study: PubMed 37172782Teabagy S, Wood E, Bilsbury E, Doherty S, Janardhana P, Lee DJ. Ocular immunosuppressive microenvironment and novel drug delivery for control of uveitis. Adv Drug Deliv Rev. 2023 Jul;198:114869. doi: 10.1016/j.addr.2023.114869. Epub 2023 May 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Quan D Nguyen, MD, MSc principal investigator
Stanford University Byers Eye Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intravitreal injection 440mcg and Intravitreal injection of sirolimus 880mcg in people with Uveitis and Intermediate Uveitis, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 26 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of uveitic attacks as assessed by vitreous haze and cells. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01280669, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2023.