Intravitreal Sirolimus as Therapeutic Approach to Uveitis

NCT01280669 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: NA_00046190
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Uveitis; Intermediate Uveitis; Posterior Uveitis; Panuveitis

Keywords

Non-infectious; Uveitis; Panuveitis

Outcome Measures

Primary Outcomes (1)

• Frequency of uveitic attacks as assessed by vitreous haze and cells.

  6 months

Secondary Outcomes (3)

• Incidence of adverse and serious adverse events

  6 months

• Changes in central retinal thickness

  6 months

• Steroid sparing effect

  6 months

Study Arms (2)

Group 1

EXPERIMENTAL

Intravitreal injections of 440mcg sirolimus (low-dose monthly group)

Drug: Intravitreal injection 440mcg

Group 2

EXPERIMENTAL

Intravitreal injections of 880mcg sirolimus (high-dose every other month group)

Drug: Intravitreal injection of sirolimus 880mcg

Interventions

Intravitreal injection 440mcg DRUG

Intravitreal injections of sirolimus 440mcg/20mcL at baseline and months 1, 2, 3, 4, and 5.

Also known as: Low-dose, Monthly

Group 1

Intravitreal injection of sirolimus 880mcg DRUG

Intravitreal injection of 880mcg/20mcL sirolimus at baseline and months 2 and 4.

Also known as: High-dose, Bi-monthly

Group 2

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 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
• 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.

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 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;
• 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;

Sponsors & Collaborators

• Stanford University: lead
• Santen Inc.: collaborator

Study Sites (1)

Stanford University

Palo Alto, California, 94303, United States

Location

Related Publications (1)

• 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.

  PMID: 37172782 DERIVED

MeSH Terms

Conditions

Uveitis; Uveitis, Intermediate; Uveitis, Posterior; Panuveitis

Interventions

Intravitreal Injections; Contraceptives, Oral

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Injections, Intraocular; Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses

Study Officials

• Quan D Nguyen, MD, MSc

  Stanford University Byers Eye Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 20, 2011
• First Posted: January 21, 2011
• Study Start: September 1, 2022
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: October 26, 2023

Record last verified: 2023-10

Locations

US (1)