Evaluation of Oral Minocycline in the Treatment of Geographic Atrophy Associated With Age-Related Macular Degeneration

NCT02564978 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 15020215-EI-0202
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Age-Related Macular Degeneration

Keywords

Eye Disease; Degenerative

Outcome Measures

Primary Outcomes (1)

• Difference in Square-Root Transformed GA Area Expansion Rates in the Study Eye Between the Treatment Phase and Run-in Phase Based on Fundus Autofluorescence (FAF)

  The difference in the square-root transformed GA area expansion rates in the study eye based on fundus autofluorescence (FAF) between the treatment phase (Month 9 to Month 33) and the run-in phase (baseline to Month 9) was compared using a linear spline regression model with a fixed knot at Month 9, at a Type I error rate of 2.5%.

  Run-in phase (baseline to Month 9) before initiation of IP and 24 months treatment phase after initiation of IP (Month 9 to Month 33)

Secondary Outcomes (5)

• Difference in Square-root Transformed GA Area Expansion Rates Between the Treatment Phase and Run-in Phase Based on Fundus Autofluorescence (FAF)

  Run-in phase (baseline to Month 9) before initiation of IP and 24 months treatment phase after initiation of IP (Month 9 to Month 33)

• Difference in the Square-root Transformed GA Area Expansion Rates Between the Treatment Phase and Run-in Phase Based on Color Fundus Photography (CFP)

  Run-in phase (baseline to Month 9) before initiation of IP and 24 months treatment phase after initiation of IP (Month 9 to Month 33)

• Difference in the Mean Rate of Change in Best Corrected Visual Acuity (BCVA) Between the Treatment Phase and Run-in Phase

  Run-in phase (baseline to Month 9) before initiation of IP and 24 months treatment phase after initiation of IP (Month 9 to Month 33)

• Difference in the Mean Rate of Change in Low-Luminance Visual Acuity (LLVA) Between the Treatment Phase and Run-in Phase

  Run-in phase (baseline to Month 9) before initiation of IP and 24 months treatment phase after initiation of IP (Month 9 to Month 33)

• Difference in the Mean Rate of Change of Central Retinal Thickness as Measured on Optical Coherence Tomography (OCT) Between the Treatment Phase and Run-in Phase

  Run-in phase (baseline to Month 9) before initiation of IP and 24 months treatment phase after initiation of IP (Month 9 to Month 33)

Study Arms (1)

Minocycline

EXPERIMENTAL

Oral administration of minocycline.

Drug: Minocycline

Interventions

Minocycline DRUG

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.

Minocycline

Eligibility Criteria

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

You may qualify if:

• 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:
• 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).
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Mukherjee S, Vance E, von der Emde L, Arunachalam T, De Silva T, Thavikulwat AT, Orndahl C, Nyaiburi C, Abraham M, Hammel K, Sadda SR, Chew EY, Pfau M, Wong WT, Jeffrey BG, Keenan TDL. Variation in Mesopic Retinal Sensitivity Relative to Distance from Geographic Atrophy in Age-Related Macular Degeneration. Ophthalmol Sci. 2025 Jul 8;5(6):100879. doi: 10.1016/j.xops.2025.100879. eCollection 2025 Nov-Dec.

  PMID: 40837068 RESULT

• Keenan TDL, Bailey C, Abraham M, Orndahl C, Menezes S, Bellur S, Arunachalam T, Kangale-Whitney C, Srinivas S, Karamat A, Nittala M, Cunningham D, Jeffrey BG, Wiley HE, Thavikulwat AT, Sadda S, Cukras CA, Chew EY, Wong WT. Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration: A Nonrandomized Controlled Trial. JAMA Ophthalmol. 2024 Apr 1;142(4):345-355. doi: 10.1001/jamaophthalmol.2024.0118.

  PMID: 38483382 RESULT

• Mukherjee S, Arunachalam T, Duic C, Abraham M, Orndahl C, Menezes S, Agron E, Pfau M, de Silva T, Bailey C, Thavikulwat AT, Bellur S, Sadda SR, Chew EY, Jeffrey BG, Wong WT, Keenan TDL. Structure-Function Relationships in Geographic Atrophy Based on Mesopic Microperimetry, Fundus Autofluorescence, and Optical Coherence Tomography. Transl Vis Sci Technol. 2025 Feb 3;14(2):7. doi: 10.1167/tvst.14.2.7.

  PMID: 39908134 RESULT

• Arunachalam T, Abraham M, Orndahl C, Menezes S, Mukherjee S, Duic C, Prasad M, Siddig F, Bellur S, Thavikulwat AT, Bailey C, Sadda SR, Wong WT, Chew EY, Jeffrey BG, Keenan TDL. Longitudinal Analysis of Mesopic Microperimetry in a Phase II Trial Evaluating Minocycline for Geographic Atrophy. Ophthalmol Sci. 2025 Apr 1;5(5):100783. doi: 10.1016/j.xops.2025.100783. eCollection 2025 Sep-Oct.

  PMID: 40417242 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Macular Degeneration; Eye Diseases

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Potential disadvantages of study design (each participant eye serves as own control): long study period, requirement for participants to wait to begin treatment, and more complex interpretation of safety data. Potential limitations of study: discontinuation of study drug/study in number of participants (accounted for in sample size calculations), absence of assays to analyze microglial activity.

Results Point of Contact

• Title: Tiarnan Keenan, MD, PhD, Principal Investigator, NEI
• Organization: National Institutes of Health

tiarnan.keenan@nih.gov

301-451-6330

Study Officials

• Tiarnan DL Keenan, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 1, 2015
• Study Start: December 14, 2016
• Primary Completion: September 28, 2022
• Study Completion: March 8, 2023
• Last Updated: November 18, 2025
• Results First Posted: February 1, 2024

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)