Sirolimus for Advanced Age-Related Macular Degeneration

NCT01445548 | Completed Phase 1 Results DMC

• 2 other identifiers: 11024911-EI-0249
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine whether a drug called sirolimus is safe to give to people with geographic atrophy (GA) and if it can help preserve vision in patients. GA is an advanced form of dry age-related macular degeneration (AMD). AMD affects the macula, the central part of the retina at the back of the eye needed for sharp, clear vision. There are two types of AMD, wet and dry. In dry AMD, cells in the macula die. GA may be partially caused by inflammation. Sirolimus helps prevent inflammation and therefore may help people with GA. Researchers want to see whether sirolimus can help prevent vision loss in people with GA. People at least 56 years of age who have GA related to AMD in both eyes may be eligible for this study. This study requires at least 8 visits to the National Eye Institute over 1 year. Study visits will be every 2 months for 1 year. Participants will undergo the following procedures:

• Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, and eye exams. One eye will be selected as the study eye to receive the sirolimus injections.
• Participants will have a sirolimus injection into the study eye at the first visit and every 2 months thereafter unless contraindicated. There will be a follow-up eye exam 1 month after the first injection.

Conditions

Age-Related Macular Degeneration; Geographic Atrophy

Keywords

Age-Related Macular Degeneration (AMD); Geographic Atrophy; Bilateral Geographic Atrophy; Sirolimus; Age Related Macular Degeneration; AMD

Outcome Measures

Primary Outcomes (2)

• Rate of Change in Area of Geographic Atrophy (GA), Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Study Eye at 12 Months Compared to Baseline.

  Baseline and Month 12

• Rate of Change in Area of Geographic Atrophy (GA), Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Fellow Eye at 12 Months Compared to Baseline.

  Baseline and Month 12

Secondary Outcomes (17)

• Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline

  Baseline and Month 12

• Changes in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Fellow Eye at 12 Months Compared to Baseline

  Baseline and Month 12

• Absolute Change in Total Area of Macular GA, Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Study Eye at 12 Months Compared to Baseline.

  Baseline and Month 12

• Absolute Change in Total Area of Macular GA, Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Fellow Eye at 12 Months Compared to Baseline.

  Baseline and Month 12

• Relative Change in Total Area of Macular GA, Based on Masked, Digital Grading of Fundus Photography by an External Reading Center, in the Study Eye at 12 Months Compared to Baseline.

  Baseline and Month 12

Study Arms (1)

Sirolimus

EXPERIMENTAL

Participants initially received a 20 μL (440 μg) intravitreal injection sirolimus in the study eye at baseline and every two months thereafter unless contraindicated. As of September 2012, sirolimus intravitreal injections were no longer administered to participants.

Drug: Sirolimus

Interventions

Sirolimus DRUG

Also known as: Rapamune®, rapamycin

Sirolimus

Eligibility Criteria

• Age: 56 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• or older
• Must understand and sign the protocol's informed consent document
• Must have at least ½ disc area (approximately 1 mm\^2) of GA compatible with AMD present in each eye
• GA is defined as one or more well-defined and often circular patches of partial or complete depigmentation of the RPE, typically with exposure of underlying choroidal blood vessels. Even if much of the RPE appears to be preserved and large choroidal vessels are not visible, a round patch of RPE partial depigmentation may be classified as early GA. The GA in each eye must be able to be photographed in their entirety, and it must not be contiguous with any areas of peripapillary atrophy, which can complicate area measurements
• Must have at least one large druse (greater than or equal to 125 μm) in each eye
• Must not have any evidence or history of exudative disease related to AMD in either eye as determined by a recent fluorescein angiogram performed within 4 months of study enrollment
• Must have a steady fixation in both eyes in the foveal or parafoveal area and media clear enough for good quality photographs
• Must have visual acuity of 20/400 or better in each eye
• Female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse, or agree to practice two acceptable methods of contraception throughout the course of the study and four months after their last study injection. Acceptable methods of contraception 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 (hysterectomy or tubal ligation).

You may not qualify if:

• Actively receiving study therapy in another investigational study
• Unable to comply with study procedures or follow-up visits
• Evidence of an ocular disease other than AMD in either eye that may confound the outcome of the study (e.g., diabetic retinopathy with 10 or more hemorrhages or microaneurysms, uveitis, pseudovitelliform macular degeneration moderate/severe myopia)
• Has any of the following: a) a history of macular laser, b) a history of photodynamic therapy (PDT), c) received an intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent for wet/exudative AMD at any point, or d) received an intravitreal injection of any other agent (not an anti-VEGF agent) within four months prior to study enrollment
• Participants currently taking or who have previously taken AREDS vitamin supplementation are not excluded.
• Has had a vitrectomy
• Expected to need ocular surgery during the course of the trial
• Has undergone lens removal in the last three months or yttrium aluminum- garnet (YAG) laser capsulotomy within the last month
• On chemotherapy
• On immunosuppressive medication
• On ocular or systemic medications known to be toxic to the lens, retina or optic nerve
• History of ocular herpes simplex virus (HSV)
• Has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control)
• Has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years
• Has laboratory values outside normal limits and considered clinically significant by the investigator

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Klein R, Klein BE, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997 Jan;104(1):7-21. doi: 10.1016/s0161-6420(97)30368-6.

  PMID: 9022098 BACKGROUND

• Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1992 Jun;99(6):933-43. doi: 10.1016/s0161-6420(92)31871-8.

  PMID: 1630784 BACKGROUND

• Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science. 2005 Apr 15;308(5720):421-4. doi: 10.1126/science.1110189. Epub 2005 Mar 10.

  PMID: 15761121 BACKGROUND

• Petrou PA, Cunningham D, Shimel K, Harrington M, Hammel K, Cukras CA, Ferris FL, Chew EY, Wong WT. Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial. Invest Ophthalmol Vis Sci. 2014 Dec 18;56(1):330-8. doi: 10.1167/iovs.14-15877.

  PMID: 25525171 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Macular Degeneration; Geographic Atrophy

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Wai T. Wong, MD, PhD
• Organization: National Eye Institute

wongw@nei.nih.gov

301-496-7566

Study Officials

• Wai T Wong, MD, PhD

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 3, 2011
• Study Start: September 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: February 1, 2014
• Last Updated: July 7, 2021
• Results First Posted: May 9, 2014

Record last verified: 2014-05

Locations

US (1)