Evaluation of Oral Minocycline in the Treatment of Geographic Atrophy Associated With Age-Related Macular Degeneration
Condition: Age-Related Macular Degeneration
MeSH terms: Macular Degeneration; Geographic Atrophy; Atrophy
Intervention: Minocycline
Intervention description: Adult participants will be instructed to take their prescribed IP orally two times a day, once in the morning and once in the evening, approximately 12 hours apart. The capsules will be dispensed to the participant in a tight, light-resistant container as defined in the USP in three-month supply aliquots. Starting at Month 9 and continuing at Month 12, a three-month supply will be dispensed to the participant during the study visit or mailed to the participant. Participants will be given an instruction sheet for taking the prescribed IP. Starting at Month 15 participants will receive two bottles for a six-month supply. The IP should be stored between 15-30 degrees C (or 59-86 degrees F).They should be protected from light, moisture, and excessive heat. Participants will be required to bring their bottles of IP to each appropriate visit for capsule counts for compliance monitoring.
Intervention MeSH terms: Minocycline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: Eye Disease; Degenerative

Summary:

      Background:

      Age-related macular degeneration (AMD) is the main reason older people lose their vision. It
      affects the macula, the center of the retina needed for sharp, clear vision. Researchers want
      to see if an antibiotic can help people with an advanced form of AMD, Geographic Atrophy
      (GA).

      Objective:

      To see if minocycline is safe for people with GA and if it helps preserve their vision.

      Eligibility:

      People age 55 and older who have GA in at least one eye.

      Design:

      Participants will be screened with physical exam, medical history, blood tests, and eye exam.

      Participants will take minocycline. They will take 1 pill twice a day for at least 3 years.

      Participants will have a minimum of 11 study visits. (But they are not every 3 months.). At
      each visit, participants will have a medical history. They may have:

      Blood tests.

      Eye exam. Vision, eye pressure, and eye movements will be checked. The pupils may be dilated.
      The inside of the eyes may be photographed.

      Their thyroid gland felt while they swallow.

      Microperimetry. They will sit in front of a computer and press a button when they see a light
      on the screen.

      Fluorescein angiography. An intravenous line (IV) will be placed in an arm vein. A dye called
      fluorescein will be placed in the IV and travel through the veins to the blood vessels in the
      eyes. A camera will take pictures of the dye as it flows through the eye blood vessels.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        To be eligible, the following inclusion criteria must be met, where applicable:

          -  Participant must be 55 years of age or older.

          -  Participant must understand and sign the protocol s informed consent document.

          -  Participant must have evidence of early or intermediate AMD as defined by
             characteristic presence of drusen and/or pigmentary changes.

          -  Participant must be able to swallow capsules.

          -  Participant must have normal renal function and liver function or have mild
             abnormalities not above grade 1 as defined by the Common Terminology Criteria for
             Adverse Events v4.0 (CTCAE).

          -  Participant must agree to minimize exposure to sunlight or artificial ultraviolet (UV)
             rays and to wear protective clothing, sunglasses and sunscreen (minimum sun protection
             factor (SPF) 15) if s/he must be out in the sun.

          -  Any female participant of childbearing potential (see Appendix 1 for definition) must
             have a negative pregnancy test at screening and be willing to undergo pregnancy tests
             throughout the study.

          -  Any female participant of childbearing potential (see Appendix 1 for definition) and
             any male participant able to father children must have (or have a partner who has) had
             a hysterectomy or vasectomy, be completely abstinent* from intercourse or must agree
             to practice two acceptable methods of contraception throughout the course of the study
             and for at least one week after investigational product (IP) discontinuation.
             Acceptable methods of contraception include:

               1. hormonal contraception (i.e., birth control pills, injected hormones, dermal
                  patch or vaginal ring),

               2. intrauterine device,

               3. barrier methods (diaphragm, condom) with spermicide, or,

               4. surgical sterilization (hysterectomy or tubal ligation).

                    -  Abstinence is only acceptable when it is the participant s preferred and
                       usual lifestyle choice. Periodic abstinence (e.g., calendar, ovulation,
                       symptothermal, post-ovulation methods) and withdrawal are not acceptable
                       methods of contraception.

        EXCLUSION CRITERIA:

        A participant is not eligible if any of the following exclusion criteria are present.

          -  Participant is actively receiving study therapy in another investigational study.

          -  Any female participant of childbearing potential (see Appendix 1 for definition) that
             is pregnant, breast-feeding or planning to become pregnant during the study.

          -  Participant is expected to be unable to comply with study procedures or follow-up
             visits.

          -  Participant is on ocular or systemic medications known to be toxic to the lens, retina
             or optic nerve (e.g., ethambutol, chloroquine, or hydroxychloroquine).

          -  Participant has a condition that would preclude participation in the study (e.g.,
             unstable medical status including blood pressure and glycemic control) by interfering
             with the participant s ability to engage in the required protocol evaluation and
             testing and/or comply with study visits.

          -  Participant has a history of chronic renal failure requiring dialysis or kidney
             transplant.

          -  Participant has a history of chronic hepatitis or liver failure.

          -  Participant has a history of thyroid cancer.

          -  Participant has an allergy or hypersensitivity to minocycline or any drug in the
             tetracycline family.

          -  Participant is currently taking minocycline or another tetracycline medication.

          -  Participant is taking any medication that could adversely interact with minocycline
             such as methoxyflurane.

          -  Participant has a prior history of idiopathic intracranial hypertension.

        STUDY EYE ELIGIBILITY CRITERIA:

        The participant must have at least one eye meeting all inclusion criteria and none of the
        exclusion criteria listed below.

        STUDY EYE INCLUSION CRITERIA:

          -  The study eye must have greater than 1/2 disc area (approximately 1 mm(2)) of GA
             compatible with dry AMD. 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 the study 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.

          -  The total area of GA lesions combined should be less than 7.0 MPS disc areas (DA)
             (17.78 mm(2)) as evident on FAF imaging.

          -  The VA of the study eye should be greater than or equal to19 E-ETDRS letters (i.e.,
             20/400 or better).

          -  The study eye must have clarity of ocular media and degree of pupil dilation
             sufficient to permit adequate fundus photographs.

        STUDY EYE EXCLUSION CRITERIA:

          -  Current evidence of choroidal neovascularization (CNV) as determined by the treating
             physician or a history of treatments for CNV

          -  Evidence of retinal atrophy due to causes other than atrophic AMD.

          -  Current evidence or history of ocular disorders in the study eye that in the opinion
             of the investigator confounds study outcome measures, including (but not limited to):

               1. non-proliferative diabetic retinopathy involving 10 or more hemorrhages or
                  microaneurysms, or active proliferative diabetic retinopathy

               2. Branch or central retinal vein or artery occlusion

               3. Macular hole

               4. Pathologic myopia

               5. Uveitis

               6. Pseudovitelliform maculopathy

          -  History of vitreoretinal surgery.

          -  Need for ocular surgery during the course of the study.

          -  Recent history of lens removal (less than 3 months) or Yttrium Aluminum Garnet (YAG)
             laser capsulotomy (less than 1 month).