Sirolimus as Therapeutic Approach to Uveitis

NCT00908466 | Completed Phase 1 Results

• 1 other identifier: NA_00028588
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Uveitis; Intermediate Uveitis; Posterior Uveitis; Panuveitis

Keywords

Non-infectious; Uveitis; Panuveitis

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (1)

• Change From Baseline VA by ETDRS

  6 and 12 months

Study Arms (2)

Intravitreal Injection

EXPERIMENTAL

Will receive intravitreal injections of sirolimus 352 µg in study eye on Days 0, 60, and 120.

Drug: Sirolimus (rapamycin)

Subconjunctival Injection

EXPERIMENTAL

Will receive subconjunctival injections of sirolimus 1320 µg in the study eye on Days 0, 60, and 120.

Drug: Sirolimus (rapamycin)

Interventions

Sirolimus (rapamycin) DRUG

Will receive intravitreal injections of sirolimus (rapamycin) 352 µg in study eye on Days 0, 60, and 120.

Also known as: Rapamycin, Rapamune, Sirolimus

Intravitreal Injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).

You may not qualify if:

• 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:
• 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;

Sponsors & Collaborators

• Johns Hopkins University: lead
• MacuSight, Inc.: collaborator

Study Sites (1)

Wilmer Eye Institute at Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• 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.

  PMID: 25918559 DERIVED

MeSH Terms

Conditions

Uveitis; Uveitis, Intermediate; Uveitis, Posterior; Panuveitis

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Quan Dong Nguyen, MD, MSc
• Organization: University of Nebraska

quan.nguyen@unmc.edu

4025591855

Study Officials

• Quan D Nguyen, MD, MSc

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2009
• First Posted: May 25, 2009
• Study Start: July 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: February 1, 2013
• Last Updated: August 20, 2018
• Results First Posted: August 20, 2018

Record last verified: 2017-12

Locations

US (1)