UveitisPhase 1SAVENCT00908466
Sirolimus as Therapeutic Approach to Uveitis
A Phase 1 study testing Sirolimus (rapamycin) in people with Uveitis and Intermediate Uveitis, run by Johns Hopkins University at 1 site in United States.
Trial summary
The purpose of this study is to find out about the safety and effectiveness of the study drug, sirolimus, in patients with uveitis and to utilize the potential effectiveness of sirolimus, and yet to avoid the potential complications of systemic use of the drug. 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?
- Sirolimus (rapamycin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2009to Feb 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 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;
- 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 other treatment; or,
- are receiving prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) and/or at least 1 other systemic immunosuppressant; or, b. Have inactive disease, defined as having 0.5+ Vitreous Haze or less and a grade of 0.5+ Vitreous Cell Count or less (SUN scale), and:
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- are receiving prednisone <10 mg/day (or equivalent dose of another corticosteroid) and/or at least 1 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 or subconjunctival treatment;
- Best-corrected (ETDRS) visual acuity of 20/40 to 20/400 (approximately 70 to 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 the uveitis, and the uveitis in the fellow eyes, in the opinion of the investigator, cannot be controlled with standard local therapies alone;
- Any significant ocular disease that could compromise vision in the study eye. These include, but are not limited to:
- Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or non-proliferative diabetic retinopathy (NPDR) that compromise the vision.
- Age-related macular degeneration;
- Myopic degeneration with active subfoveal choroidal neovascularization.
- Any of the following treatments within 90 days prior to Day 0 or anticipated use of any of the following treatments to the study eye:
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- Intravitreal injections (including but not limited to steroids or anti-vascular endothelial growth factors);
- Posterior subtenon's steroids.
- 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;
- If the patient has had glaucoma surgery (trabeculectomy or aqueous shunt device), there must be adequate conjunctiva
- History of vitreoretinal surgery or scleral buckling
- 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 intraocular pressure (IOP) <25 mmHg are allowed to participate);
- Pupillary dilation inadequate for quality stereoscopic fundus photography in the study eye;
- Media opacity that would limit clinical visualization;
- 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.
United States1 site
Wilmer Eye Institute at Johns Hopkins University
Baltimore, Maryland, 21287
About this study
Official title: A Phase 1, Open-label, Randomized Clinical Study to Assess the Safety, Tolerability and Bioactivity of Intravitreal and Subconjunctival Injection of Sirolimus in Patients With Non-infectious Uveitis
The purpose of this study is to find out about the safety and effectiveness of the study drug, sirolimus, in patients with uveitis and to utilize the potential effectiveness of sirolimus, and yet to avoid the potential complications of systemic use of the drug. In this study, the investigators will administer sirolimus either around (subconjunctival injection) or inside the eye (intravitreal injection). 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 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
- Sirolimus (rapamycin)
- 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.
Sirolimus (rapamycin)Drug
Also called Rapamycin, Rapamune, Sirolimus
Will receive intravitreal injections of sirolimus (rapamycin) 352 µg in study eye on Days 0, 60, and 120.
Sirolimus (rapamycin)Drug
Also called Rapamycin, Rapamune, Sirolimus
Will receive subconjunctival injections of sirolimus 1320 µg in the study eye on Days 0, 60, and 120.
| Study group | Role | What they receive |
|---|---|---|
| Intravitreal Injection | Experimental | Will receive intravitreal injections of sirolimus 352 µg in study eye on Days 0, 60, and 120. Receives: Drug: Sirolimus (rapamycin) |
| Subconjunctival Injection | Experimental | Will receive subconjunctival injections of sirolimus 1320 µg in the study eye on Days 0, 60, and 120. Receives: Drug: Sirolimus (rapamycin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With at Least 2-step Decrease in Vitreous Haze (VH)
Vitreous Haze is calculated using a 9 step photographic haze in uveitis patients using fundus photograph
Measured: 6 months
Secondary outcomes (1)
Change From Baseline VA by ETDRS
Measured: 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2009 (estimated)
- Study startJul 2009
- Primary completionJul 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 Johns Hopkins 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- MacuSight, Inc.
- Responsible party
- Sponsor
- Investigators
- Quan D Nguyen, MD, MSc, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00908466
- Sponsor's protocol ID
- NA_00028588
- Acronym
- SAVE
- Status last verified
- Dec 2017
- First submitted
- 30 Apr 2009
- Last updated
- 20 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Vigil EM, Sepah YJ, Watters AL, Sadiq MA, Ansari M, Bittencourt MG, Ibrahim MA, Do DV, Nguyen QD. Assessment of changes in quality of life among patients in the SAVE Study - Sirolimus as therapeutic Approach to uVEitis: a randomized study to assess the safety and bioactivity of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis. J Ophthalmic Inflamm Infect. 2015 Apr 18;5:13. doi: 10.1186/s12348-015-0044-1. eCollection 2015.
PubMed 25918559
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Randomized Clinical Study to Assess the Safety, Tolerability and Bioactivity of Intravitreal and Subconjunctival Injection of Sirolimus in Patients With Non-infectious Uveitis
- ClinicalTrials.gov ID
- NCT00908466
- Acronym / sponsor ID
- SAVE / NA_00028588
- Conditions
- Uveitis, Intermediate Uveitis, Posterior Uveitis, Panuveitis
- Keywords
- Non-infectious, Uveitis, Panuveitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- MacuSight, Inc.
- Study start
- Jul 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 25 May 2009 (estimated)
- Results
- Posted 20 Aug 2018
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 the study drug, sirolimus, in patients with uveitis and to utilize the potential effectiveness of sirolimus, and yet to avoid the potential complications of systemic use of the drug. In this study, the investigators will administer sirolimus either around (subconjunctival injection) or inside the eye (intravitreal injection). 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 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 |
|---|---|---|
| Intravitreal Injection | Experimental | Drug: Sirolimus (rapamycin)Will receive intravitreal injections of sirolimus 352 µg in study eye on Days 0, 60, and 120. |
| Subconjunctival Injection | Experimental | Drug: Sirolimus (rapamycin)Will receive subconjunctival injections of sirolimus 1320 µg in the study eye on Days 0, 60, and 120. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Males and females greater than or equal to 18 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;
- 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 or subconjunctival treatment;
Key exclusion criteria (21 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 the uveitis, and the uveitis in the fellow eyes, in the opinion of the investigator, cannot be controlled with standard local therapies alone;
- Any significant ocular disease that could compromise vision in the study eye. These include, but are not limited to:
- Any of the following treatments within 90 days prior to Day 0 or anticipated use of any of the following treatments to the study eye:
- 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;
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 |
|---|---|---|
| Sirolimus (rapamycin)Also: Rapamycin, Rapamune, SirolimusWill receive intravitreal injections of sirolimus (rapamycin) 352 µg in study eye on Days 0, 60, and 120. | Drug | Intravitreal Injection |
| Sirolimus (rapamycin)Also: Rapamycin, Rapamune, SirolimusWill receive subconjunctival injections of sirolimus 1320 µg in the study eye on Days 0, 60, and 120. | Drug | Subconjunctival Injection |
Primary outcome
Number of Participants With at Least 2-step Decrease in Vitreous Haze (VH)
Time frame: 6 months
Vitreous Haze is calculated using a 9 step photographic haze in uveitis patients using fundus photograph
1 secondary outcome
Change From Baseline VA by ETDRS
Time frame: 6 and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25918559Vigil EM, Sepah YJ, Watters AL, Sadiq MA, Ansari M, Bittencourt MG, Ibrahim MA, Do DV, Nguyen QD. Assessment of changes in quality of life among patients in the SAVE Study - Sirolimus as therapeutic Approach to uVEitis: a randomized study to assess the safety and bioactivity of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis. J Ophthalmic Inflamm Infect. 2015 Apr 18;5:13. doi: 10.1186/s12348-015-0044-1. eCollection 2015.
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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
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sirolimus (rapamycin) in people with Uveitis and Intermediate Uveitis, run by Johns Hopkins 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 11 inclusion and 21 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: finished, as of the sponsor's last update on 20 Aug 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With at Least 2-step Decrease in Vitreous Haze (VH) (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 NCT00908466, 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 20 Aug 2018; AzTrials last refreshed its copy on 6 Nov 2026.