Retinal Vein Occlusion
Conditions
Keywords
Visual Acuity, Retinal Vein Occlusion, Central Retinal Vein Occlusion, CRVO
Brief summary
Background: \- Central retinal vein occlusion (CRVO) is a blockage of the main vein that carries blood away from the retina in the back of the eye. It can lead to macular edema, a swelling of the retina that is a common source of vision loss. Studies suggest that inflammation might be a cause. Minocycline is a drug that might help prevent cells involved in inflammation from becoming activated. It is approved for use as an antibiotic, but it has not yet been tested to see if it can treat CRVO. Objectives: \- To test the safety and effectiveness of minocycline as a treatment for central retinal vein occlusion. Eligibility: \- Individuals at least 18 years of age who have central retinal vein occlusion in at least one eye, with vision between 20/32 and 20/200. Design: * This study lasts 2 years, with at least 25 visits. * Participants will be screened with a physical exam and medical history. They will also have blood tests and an eye exam. One eye will be selected as the study eye to receive the medicine. * Participants will take minocycline or a placebo pill twice a day, about 12 hours apart, for 2 years. * Participants will have monthly visits for blood tests and full eye exams to study the effect of the treatment. Other exams may include thyroid tests and eye imaging studies. Those in the study may also receive injections of a drug to prevent the growth of new blood vessels in the eye.
Detailed description
Objective: Retinal vein occlusions (RVOs) are significant sources of vision loss, affecting mostly healthy people over 55 years of age. The common source of vision loss is the macular edema accompanying the retinal injury. Very recently, studies employing monthly anti-vascular endothelial growth factor (VEGF) treatments have demonstrated a benefit to this line of treatment; however, the duration of effectiveness appears to be short lived and the length of time needed for these monthly injections remains unknown. A histologic study of human retinas with retinal vein occlusions found the presence of activated microglia. Microglia are capable of migrating through the retina to sites of inflammation to associate closely with neurons and the vasculature, and are key cellular players in the mediation of processes of chronic inflammation. For these reasons, microglia represent a promising cellular target for forms of therapy that limit the deleterious inflammatory changes found in vein occlusions. Minocycline, a second-generation tetracycline, has been shown to exhibit anti-inflammatory properties, including microglial inhibition. The objective of this study is to investigate the safety and potential efficacy of minocycline as a microglia inhibitor in participants with central retinal vein occlusion (CRVO). Study Population: A minimum of 10 and a maximum of 20 participants who meet the eligibility criteria may be enrolled. Eligibility criteria include: foveal center-involved macular edema secondary to a CRVO, retinal thickness in the central subfield \>350 microns as measured by optical coherence tomography (OCT); and visual acuity (VA) between 20/32 and 20/200 in the study eye. Design: In this pilot, double-masked, randomized multi-center study, participants will receive monthly bevacizumab injections for the first three months, followed by PRN dosing. In addition, participants will take an oral dose of 100 mg of minocycline or placebo twice daily for 24 months. During each monthly visit, participants will have their visual acuity measured and will undergo OCT testing to measure retinal thickness. At the Month 3 visit and thereafter, participants will be evaluated for improvement and worsening and will be eligible for additional bevacizumab treatment and/or investigational product (IP) depending on which criteria they fulfill. Additionally, at Month 12, participants will also be evaluated for no improvement. Outcome Measures: The primary outcome is the difference in mean change in best-corrected visual acuity (BCVA), as measured in ETDRS letters, between the minocycline and placebo groups in the study eye at 12 months compared to baseline. Secondary outcomes include the difference between the minocycline and placebo groups in the number of intravitreal bevacizumab injections between 12 and 24 months and baseline, changes in mean macular sensitivity as measured by microperimetry at 3, 6, 12, 18 and 24 months compared to baseline, the mean change in BCVA at 24 months compared to baseline, changes in retinal thickness as measured by OCT at 6, 12, 18 and 24 months compared to baseline, number of participants improving greater than or equal to 1 logOCT scale step at 12 and 24 months compared to baseline, as well as and changes in fluid leakage in the macula as demonstrated by fluorescein angiography at 12 and 24 months compared to baseline. Safety outcomes include the number of participant withdrawals, number and severity of systemic and ocular toxicities and the number of adverse events (AEs).
Interventions
DRUGBevacizumab
1.25 mg bevacizumab injection
DRUGMinocycline
100 mg pink opaque capsule
DRUGPlacebo
Placebo
Sponsors
National Eye Institute (NEI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: To be eligible, the following participant-level inclusion criteria must be met, where applicable: * Participant is 18 years of age or older. * Participant must understand and sign the protocol s informed consent document. * Female participants of childbearing potential must not be pregnant or breast-feeding and must be willing to undergo serum (BRC sites only) and urine pregnancy tests throughout the study. * For the NEI Site: 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 must agree to practice two acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation (based on the half life of minocycline which is 11-22 hours). 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). * Oral birth control pills must be used with caution as minocycline decreases the effectiveness of some oral contraceptives. Participants already taking oral contraceptives may continue to use them, but must agree to use at least one other method of birth control while on study. * For the BRC Sites: 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, or be completely abstinent from intercourse. Male participants or male partners (of female participants) who have not had a vasectomy or are not abstinent are required to use a condom with spermicide throughout the course of the study and for one week after study medication discontinuation (based on the half life of minocycline which is 11-22 hours). Female participants of childbearing potential or female partners (of male participants) of childbearing potential must practice one of the below acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation: * hormonal contraception (i.e., birth control pills\*, injected hormones, dermal patch or vaginal ring), * intrauterine device, * barrier methods (e.g., diaphragm) 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. \*Oral birth control pills must be used with caution as minocycline decreases the effectiveness of some oral contraceptives. Participants already taking oral contraceptives may continue to use them, but must agree to use at least one other method of birth control while on study. It should be noted that two forms of contraception (as specified above) will be used by sexually active participants for the duration of the study and for one week after study medication discontinuation. * Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new medication during the course of this study. * 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 AEs v4.0 (CTCAE). * Participant must agree to minimize exposure to sunlight or artificial UV rays and to wear protective clothing, sunglasses, and sunscreen (minimum SPF 15) if s/he must be out in the sun. * Participant has at least one eye that meets the study eye criteria listed in the Study Eye Eligibility Criteria below.
Exclusion criteria
A participant is not eligible if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome is the Comparison Between the Minocycline and Placebo Groups of the Mean Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline. | Baseline to Month 12 | The primary outcome measure is the mean change in best-corrected visual acuity (BCVA), as measured in ETDRS letters in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline | Baseline to Month 24 | Improvement of ≥ 1 logOCT scale step is defined as a decrease of ≥ 1-step on the logOCT scale. A 1-step decrease is equivalent to at least a 20% improvement of central macular thickness. |
| Number of Bevacizumab Injections From Baseline to 12 Months | Baseline to Month 12 | The outcome measure is the number of bevacizumab injections administered to participants between baseline and 12 months. |
| Number of Bevacizumab Injections From Baseline to 24 Months | Baseline to Month 24 | The outcome measure is the number of bevacizumab injections administered to participants between baseline and 24 months. |
| Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 3 Months Compared to Baseline | Baseline to Month 3 | The outcome measure is the mean change in macular sensitivity in the study eye at 3 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 3 months. |
| Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 6 Months Compared to Baseline | Baseline to Month 6 | The outcome measure is the mean change in macular sensitivity in the study eye at 6 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 6 months. |
| Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 12 Months Compared to Baseline | Baseline to Month 12 | The outcome measure is the mean change in macular sensitivity in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months. |
| Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 18 Months Compared to Baseline | Baseline to Month 18 | The outcome measure is the mean change in macular sensitivity in the study eye at 18 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 18 months. |
| Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline | Baseline to Month 12 | Improvement of ≥ 1 logOCT scale step is defined as a decrease of ≥ 1-step on the logOCT scale. A 1-step decrease is equivalent to at least a 20% improvement of central macular thickness. |
| Mean Change in the ETDRS BCVA in the Study Eye at 24 Months Compared to Baseline | Baseline to Month 24 | The outcome measure is the mean change in best-corrected visual acuity (BCVA), as measured in ETDRS letters in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months. |
| Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 6 Months Compared to Baseline | Baseline to Month 6 | The outcome measure is the mean change in central retinal thickness in the study eye at 6 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 6 months. |
| Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline | Baseline to Month 12 | The outcome measure is the mean change in central retinal thickness in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months. |
| Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 18 Months Compared to Baseline | Baseline to Month 18 | The outcome measure is the difference in the mean change in central retinal thickness in the study eye at 18 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 18 months. |
| Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 24 Months Compared to Baseline | Baseline to Month 24 | The outcome measure is the mean change in central retinal thickness in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months. |
| Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline | Baseline to Month 12 | The outcome measure is the number of participants experiencing changes in fluid leakage in the macula of the study eye as demonstrated by fluorescein angiography at 12 months compared to baseline. The counts presented are the number of participants experiencing decrease, increase, or no change in fluid leakage from baseline. |
| Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline. | Baseline to Month 24 | The outcome measure is the the number of participants experiencing changes in fluid leakage in the macula of the study eye as demonstrated by fluorescein angiography at 24 months compared to baseline. The counts presented are the number of participants experiencing decrease, increase, or no change in fluid leakage from baseline. |
| Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 24 Months Compared to Baseline | Baseline to Month 24 | The outcome measure is the mean change in macular sensitivity in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Minocycline Participants injected with bevacizumab for three months followed by PRN dosing and 100mg minocycline twice daily for 24 months
Minocycline: 100 mg pink opaque capsule | 4 |
| Placebo Participants injected with bevacizumab for three months followed by PRN dosing and placebo twice daily for 24 months
Placebo: Placebo | 2 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Minocycline | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Continuous | 71.0 years STANDARD_DEVIATION 8.8 | 66.0 years STANDARD_DEVIATION 11.1 | 69.3 years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 2 |
| other Total, other adverse events | 4 / 4 | 2 / 2 |
| serious Total, serious adverse events | 1 / 4 | 1 / 2 |
Outcome results
Primary
The Primary Outcome is the Comparison Between the Minocycline and Placebo Groups of the Mean Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline.
The primary outcome measure is the mean change in best-corrected visual acuity (BCVA), as measured in ETDRS letters in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months.
Time frame: Baseline to Month 12
Population: The primary outcome analysis population includes those participants who were exposed to IP and were followed up for at least 12 months. One participant in the minocycline group was excluded from the analysis because their Month 12 data was not recorded due to their withdrawal from the study prior to Month 12, and one participant in the placebo group was excluded due to missing ETDRS BCVA letters data at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | The Primary Outcome is the Comparison Between the Minocycline and Placebo Groups of the Mean Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline. | 13.3 ETDRS letters | Standard Deviation 7 |
| Placebo | The Primary Outcome is the Comparison Between the Minocycline and Placebo Groups of the Mean Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline. | -2.0 ETDRS letters | — |
Secondary
Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline
The outcome measure is the number of participants experiencing changes in fluid leakage in the macula of the study eye as demonstrated by fluorescein angiography at 12 months compared to baseline. The counts presented are the number of participants experiencing decrease, increase, or no change in fluid leakage from baseline.
Time frame: Baseline to Month 12
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. Two participants in the minocycline group were excluded from the analysis: one because their Month 12 data was not recorded due to withdrawal from the study prior to Month 12, and one due to missing data for fluid leakage at the Month 12 visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline | Decrease | 2 participants |
| Minocycline | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline | Increase | 0 participants |
| Minocycline | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline | No Change | 0 participants |
| Placebo | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline | Decrease | 1 participants |
| Placebo | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline | Increase | 1 participants |
| Placebo | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 12 Months Compared to Baseline | No Change | 0 participants |
Secondary
Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline.
The outcome measure is the the number of participants experiencing changes in fluid leakage in the macula of the study eye as demonstrated by fluorescein angiography at 24 months compared to baseline. The counts presented are the number of participants experiencing decrease, increase, or no change in fluid leakage from baseline.
Time frame: Baseline to Month 24
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. Two participants in the minocycline group were excluded from the analysis because their Month 24 data was not recorded due to withdrawal from the study prior to Month 24, and one participant in the placebo group was excluded due to missing data for fluid leakage at the Month 24 visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline. | Decrease | 2 participants |
| Minocycline | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline. | Increase | 0 participants |
| Minocycline | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline. | No Change | 0 participants |
| Placebo | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline. | Decrease | 1 participants |
| Placebo | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline. | Increase | 0 participants |
| Placebo | Changes in Fluid Leakage in the Macula of the Study Eye as Demonstrated by Fluorescein Angiography at 24 Months Compared to Baseline. | No Change | 0 participants |
Secondary
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 12 Months Compared to Baseline
The outcome measure is the mean change in macular sensitivity in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months.
Time frame: Baseline to Month 12
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. One participant in the minocycline group was excluded from the analysis because their Month 12 data was not recorded due to withdrawal from the study prior to Month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 12 Months Compared to Baseline | -1.7 db | Standard Deviation 5.5 |
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 12 Months Compared to Baseline | 1.3 db | Standard Deviation 0.6 |
Secondary
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 18 Months Compared to Baseline
The outcome measure is the mean change in macular sensitivity in the study eye at 18 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 18 months.
Time frame: Baseline to Month 18
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. Two participants in the minocycline group were excluded from the analysis because their Month 18 data was not recorded due to withdrawal from the study prior to Month 18.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 18 Months Compared to Baseline | -0.9 db | Standard Deviation 4 |
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 18 Months Compared to Baseline | 4.5 db | Standard Deviation 0.3 |
Secondary
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 24 Months Compared to Baseline
The outcome measure is the mean change in macular sensitivity in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months.
Time frame: Baseline to Month 24
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. Two participants in the minocycline group were excluded from the analysis because their Month 24 data was not recorded due to withdrawal from the study prior to Month 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 24 Months Compared to Baseline | -1.5 db | Standard Deviation 3.3 |
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 24 Months Compared to Baseline | 3.9 db | Standard Deviation 4.2 |
Secondary
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 3 Months Compared to Baseline
The outcome measure is the mean change in macular sensitivity in the study eye at 3 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 3 months.
Time frame: Baseline to Month 3
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. One participant in the minocycline group was excluded due to missing macular sensitivity data at Month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 3 Months Compared to Baseline | 0.8 db | Standard Deviation 2.2 |
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 3 Months Compared to Baseline | 3.4 db | Standard Deviation 0.2 |
Secondary
Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 6 Months Compared to Baseline
The outcome measure is the mean change in macular sensitivity in the study eye at 6 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 6 months.
Time frame: Baseline to Month 6
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. One participant in the minocycline group was excluded from the analysis because their Month 6 data was not recorded due to withdrawal from the study prior to Month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 6 Months Compared to Baseline | 0.3 db | Standard Deviation 2.8 |
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 6 Months Compared to Baseline | 1.1 db | Standard Deviation 4.5 |
Secondary
Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline
The outcome measure is the mean change in central retinal thickness in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months.
Time frame: Baseline to Month 12
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. One participant in the minocycline group was excluded from the analysis because their Month 12 data was not recorded due to withdrawal from the study prior to Month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline | -145.3 micrometers | Standard Deviation 259.1 |
| Placebo | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline | -458.5 micrometers | Standard Deviation 313.2 |
Secondary
Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 18 Months Compared to Baseline
The outcome measure is the difference in the mean change in central retinal thickness in the study eye at 18 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 18 months.
Time frame: Baseline to Month 18
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. Two participants in the minocycline group were excluded from the analysis because their Month 18 data was not recorded due to withdrawal from the study prior to Month 18.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 18 Months Compared to Baseline | -52.0 micrometers | Standard Deviation 169.7 |
| Placebo | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 18 Months Compared to Baseline | -480.5 micrometers | Standard Deviation 118.1 |
Secondary
Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 24 Months Compared to Baseline
The outcome measure is the mean change in central retinal thickness in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months.
Time frame: Baseline to Month 24
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. Two participants in the minocycline group were excluded from the analysis because their Month 24 data was not recorded due to withdrawal from the study prior to Month 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 24 Months Compared to Baseline | -227.0 micrometers | Standard Deviation 84.9 |
| Placebo | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 24 Months Compared to Baseline | -346.0 micrometers | Standard Deviation 41 |
Secondary
Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 6 Months Compared to Baseline
The outcome measure is the mean change in central retinal thickness in the study eye at 6 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 6 months.
Time frame: Baseline to Month 6
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. One participant in the minocycline group was excluded from the analysis because their Month 6 data was not recorded due to withdrawal from the study prior to Month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 6 Months Compared to Baseline | -272.7 micrometers | Standard Deviation 117 |
| Placebo | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 6 Months Compared to Baseline | -312.0 micrometers | Standard Deviation 128.7 |
Secondary
Mean Change in the ETDRS BCVA in the Study Eye at 24 Months Compared to Baseline
The outcome measure is the mean change in best-corrected visual acuity (BCVA), as measured in ETDRS letters in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months.
Time frame: Baseline to Month 24
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. Two participants in the minocycline group were excluded from the analysis because their Month 24 data was not recorded due to withdrawal from the study prior to Month 24, and one participant in the placebo group was excluded due to missing baseline BCVA data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Mean Change in the ETDRS BCVA in the Study Eye at 24 Months Compared to Baseline | 13 ETDRS letters | Standard Deviation 0 |
| Placebo | Mean Change in the ETDRS BCVA in the Study Eye at 24 Months Compared to Baseline | -17.0 ETDRS letters | — |
Secondary
Number of Bevacizumab Injections From Baseline to 12 Months
The outcome measure is the number of bevacizumab injections administered to participants between baseline and 12 months.
Time frame: Baseline to Month 12
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Number of Bevacizumab Injections From Baseline to 12 Months | 5.5 injections | Standard Deviation 4.4 |
| Placebo | Number of Bevacizumab Injections From Baseline to 12 Months | 10.5 injections | Standard Deviation 0.7 |
Secondary
Number of Bevacizumab Injections From Baseline to 24 Months
The outcome measure is the number of bevacizumab injections administered to participants between baseline and 24 months.
Time frame: Baseline to Month 24
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Number of Bevacizumab Injections From Baseline to 24 Months | 7.8 injections | Standard Deviation 8.8 |
| Placebo | Number of Bevacizumab Injections From Baseline to 24 Months | 16.0 injections | Standard Deviation 0 |
Secondary
Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline
Improvement of ≥ 1 logOCT scale step is defined as a decrease of ≥ 1-step on the logOCT scale. A 1-step decrease is equivalent to at least a 20% improvement of central macular thickness.
Time frame: Baseline to Month 12
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. One participant in the minocycline group was excluded from the analysis because their Month 12 data was not recorded due to their withdrawal from the study prior to Month 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Minocycline | Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline | 2 Participants |
| Placebo | Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline | 2 Participants |
Secondary
Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline
Improvement of ≥ 1 logOCT scale step is defined as a decrease of ≥ 1-step on the logOCT scale. A 1-step decrease is equivalent to at least a 20% improvement of central macular thickness.
Time frame: Baseline to Month 24
Population: The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. Two participants in the minocycline group were excluded because their Month 24 data was not recorded due to their withdrawal from the study prior to Month 24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Minocycline | Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline | 2 Participants |
| Placebo | Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline | 2 Participants |