Intravitreal Injections of Sirolimus in the Treatment of Geographic Atrophy

NCT01675947 | Terminated Phase 2 DMC

• 1 other identifier: 3368-12056
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 13

Brief Summary

This study will seek to enroll 50 persons who have central or non-central geographic atrophy (GA) associated with age-related macular degeneration (AMD). GA in treated eye must be between 0.75 disk areas (DA) and 8 DA. Eligible participants will be randomly chosen to receive one of the following treatments in the study eye:

1. 1.A 20 μL (440 μg) intravitreal (IVT) injection of sirolimus, or
2. 2.A sham treatment (subconjunctival injection of lidocaine) Participants with two (2) eligible eyes will have one eye randomly assigned to receive intravitreal sirolimus and no sham in the fellow eye.
3. 3.A clinical evaluation, including safety measures, will occur monthly.
4. 4.Vision will be measured at the screening/enrollment visit and at 2, 3, 6, 9, 12, 18 and 24 months after the first injection has occurred.
5. 5.Fundus autofluorescence will occur at screening/enrollment and at 2, 6, 12, 18 and 24 months after the first injection has occurred.
6. 6.Fundus color photography and optical coherence tomography will occur at screening/enrollment and at 6, 12, 18 and 24 months after the first injection has occurred.

Conditions

Geographic Atrophy

Outcome Measures

Primary Outcomes (1)

• Rate of change in area of geographic atrophy

  Every 6 months after enrollment for 2 years

Secondary Outcomes (1)

• Change in best-corrected visual acuity

  Every 6 months after enrollment for 2 years

Other Outcomes (1)

• Number and severity of systemic and ocular toxicities, adverse events and infections

  Monthly for 2 years

Study Arms (2)

Sirolimus

EXPERIMENTAL

Monthly 20 μL (440 μg) intravitreal injection of sirolimus

Drug: Sirolimus

Lidocaine

SHAM COMPARATOR

Monthly subconjunctival injection of 2% lidocaine

Drug: Lidocaine

Interventions

Sirolimus DRUG

Immunosuppressive agent. Blocks the T-lymphocyte activation and smooth muscle and endothelial cell proliferation that occurs in response to antigenic and cytokine (interleukin IL-2, IL-4 and IL-15) stimulation through either Ca2+-dependent or Ca2+-independent pathways. Sirolimus arrests cell cycle progression by direct interaction with two intracellular proteins (immunophilin FK binding protein 12 (FKBP-12) and the mammalian target of rapamycin (mTOR), a multifunctional serine-threonine kinase). In cells, sirolimus binds to FKBP-12, and the resulting sirolimus-FKBP-12 complex then binds to and inhibits mTOR.

Also known as: Rapamycin, Rapamune

Sirolimus

Lidocaine DRUG

Lidocaine 2%

Also known as: Xylocaine, lignocaine

Lidocaine

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55 years of age or older. Prior participation in the Age-Related Eye Disease Study 2 (AREDS2) is not required.
• Participant must understand and sign the protocol's informed consent document.
• Participant must have central or non-central geographic atrophy (GA) in at least one eye. GA should be at least 0.75 disk areas (DA) in size but no more than 8 disk areas (DA); approximately 2.54 mm2 is 1 DA. GA is defined as one or more well-defined, usually more or less circular patches of partial or complete de-pigmentation of the retinal pigment epithelium (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 de-pigmentation may still be classified as early GA.
• Participant must have a steady fixation in the study eye in the foveal or parafoveal area and media clear enough for good quality photographs.
• Participant must have visual acuity between 20/25 and 20/200 in the study eye.
• Female participants must be post-menopausal.
• Male participants with female partners capable of conceiving children will be required to use contraception during the study and for four months after their last sirolimus injection.

You may not qualify if:

• Participant is in another investigational study other than AREDS2 and actively receiving study therapy for geographic atrophy or choroidal neovascularization (CNV).
• Participant is unable to comply with study procedures or follow-up visits.
• Participant has evidence of ocular disease other than AMD in either eye that may confound the outcome of the study (e.g., glaucoma, diabetic retinopathy with 10 or more hemorrhages or microaneurysms, uveitis, pseudovitelliform macular degeneration, moderate/severe myopia).
• Participant has had a vitrectomy.
• Participant is expected to need ocular surgery during the course of the trial.
• Participant has undergone lens removal in the last three months or Yttrium Aluminium Garnet (YAG) laser capsulotomy within the last month.
• Participant is on chemotherapy.
• Participant is on immunosuppressive medication or is immunosuppressed.
• Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve.
• Participant with a history of malignancy that would compromise the 2-year study survival.
• Participant with a history of ocular herpes simplex virus (HSV).
• 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).
• History of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years that could be worsened by immunosuppression. (The risk of immunosuppression must be determined by an oncology consultation prior to enrollment.)
• Ocular or periocular inflammation or infection in either eye.
• Presence of active or inactive toxoplasmosis in the study eye.

Sponsors & Collaborators

• National Eye Institute (NEI): lead
• The Emmes Company, LLC: collaborator
• Santen Inc.: collaborator

Study Sites (13)

Loma Linda University

Loma Linda, California, 92354, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

University of Florida HSC

Jacksonville, Florida, 32209, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

Elman Retina Group

Baltimore, Maryland, 21237, United States

Location

Vision Research Foundation

Grand Rapids, Michigan, 49546, United States

Location

Charlotte Eye Ear Nose & Throat Associates

Charlotte, North Carolina, 28210, United States

Location

Scheie Eye Institute, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Palmetto Retina Center

West Columbia, South Carolina, 29169, United States

Location

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, 37909, United States

Location

Texas Retina Associates

Dallas, Texas, 75231, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Geographic Atrophy

Interventions

Sirolimus; Lidocaine

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines

Study Officials

• Emily Y Chew, MD

  National Eye Institute (NEI)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2012
• First Posted: August 30, 2012
• Study Start: February 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: February 1, 2016
• Last Updated: December 10, 2015

Record last verified: 2015-12

Locations

US (13)