Retinal Vein Occlusion
Conditions
Keywords
Minocycline, Macular Edema
Brief summary
Background: \- Branch retinal vein occlusion (BRVO) is a blockage of the small veins that carry blood away from the retina in the back of the eye. It often leads 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 BRVO. Objectives: \- To test the safety and effectiveness of minocycline as a treatment for branch retinal vein occlusion. Eligibility: \- Individuals at least 18 years of age who have branch 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. * Those in the study 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 (RVO) 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 RVOs 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 microglia inhibition. The objective of this study is to investigate the safety and efficacy of minocycline as a microglia inhibitor in participants with branch retinal vein occlusion (BRVO). Study Population: A minimum of ten 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 BRVO, retinal thickness in the central subfield greater than 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, the 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 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, the number and severity of systemic and ocular toxicities and the number of adverse events.
Interventions
DRUGMinocycline
100 mg of minocycline in a pink opaque capsule
OTHERPlacebo
Pill with inactive ingredients in a pink opaque capsule
DRUGBevacizumab
1.25 mg bevacizumab injection
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
PARTICIPANT ELIGIBILITY CRITERIA INCLUSION CRITERIA: To be eligible, the following inclusion criteria must be met, where applicable: 1. Participant is 18 years of age or older. 2. Participant must understand and sign the protocol's informed consent document. 3. 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. 4. Female participants of childbearing potential and male participants able to father children must meet the following site-specific criteria: 1. 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). * Note: 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. 2. 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). * Notes: i) 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. ii) 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. iii)) 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. 5. Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new medication during the course of the study. 6. 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). 7. 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. 8. Participant has at least one eye that meets the study eye criteria.
Exclusion criteria
A participant is not eligible if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 difference between the minocycline and placebo groups in the 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 Bevacizumab Injections From Baseline to 24 Months | Baseline to Month 24 | The outcome measure is the difference between the minocycline and placebo groups in 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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 3 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 3 months. Higher macular sensitivity (higher db) is better. |
| 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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 6 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 6 months. Higher macular sensitivity (higher db) is better. |
| 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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months. Higher macular sensitivity (higher db) is better. |
| 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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 18 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 18 months. Higher macular sensitivity (higher db) is better. |
| 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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months. Higher macular sensitivity (higher db) is better. |
| 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 difference between the minocycline and placebo groups in the 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. |
| Number of Bevacizumab Injections From Baseline to 12 Months | Baseline to Month 12 | The outcome measure is the difference between the minocycline and placebo groups in the number of bevacizumab injections administered to participants between baseline and 12 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 difference between the minocycline and placebo groups in the 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 mean difference between the minocycline and placebo groups in the 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 difference between the minocycline and placebo groups in the 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. |
| Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline | Baseline to Month 12 | The outcome measure is the difference between the minocycline and placebo groups in the number of participants experiencing an improvement of ≥ 1 logOCT scale step from baseline to Month 12. Improvement in ≥ 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 Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline | Baseline to Month 24 | The outcome measure is the difference between the minocycline and placebo groups in the number of participants experiencing an improvement of ≥ 1 logOCT scale step from baseline to Month 24. Improvement in ≥ 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 Participants Experiencing 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 difference between the between the minocycline and placebo groups in 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. |
| 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. | Baseline to Month 24 | The outcome measure is the difference between the between the minocycline and placebo groups in 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 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 difference between the minocycline and placebo groups in the 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. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
Recriutment was activated on November 18, 2011 at the NEI site and on May 25, 2018 at the BEH site. Enrollment was closed on May 13, 2019 at the NEI site and on December 31, 2019 at the BEH site.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants injected with bevacizumab for three months followed by PRN dosing and placebo twice daily for 24 months
Placebo: Pill with inactive ingredients in a pink opaque capsule | 4 |
| Minocycline Participants injected with bevacizumab for three months followed by PRN dosing and 100mg minocycline twice daily for 24 months
Minocycline: 100 mg of minocycline in a pink opaque capsule | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Placebo | Minocycline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 5 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 62.5 years STANDARD_DEVIATION 11.21 | 70.6 years STANDARD_DEVIATION 5.55 | 67.0 years STANDARD_DEVIATION 8.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 8 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment United Kingdom | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 3 participants | 4 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 4 / 4 | 5 / 5 |
| serious Total, serious adverse events | 0 / 4 | 1 / 5 |
Outcome results
Primary
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 difference between the minocycline and placebo groups in the 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline. | 5.3 ETDRS letters | Standard Deviation 9.6 |
| Minocycline | Mean Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline. | 13.0 ETDRS letters | Standard Deviation 11.3 |
95% CI: [-10.6, 26.1]
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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 12 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 12 months. Higher macular sensitivity (higher db) is better.
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 because their Month 12 data was not recorded due to withdrawal from the study prior to the Month 12 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 12 Months Compared to Baseline | 1.1 db | Standard Deviation 1.4 |
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 12 Months Compared to Baseline | -1.4 db | Standard Deviation 3.3 |
95% CI: [-7.5, 2.5]
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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 18 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 18 months. Higher macular sensitivity (higher db) is better.
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 was excluded due to missing macular sensitivity data at Month 18.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 18 Months Compared to Baseline | 0.4 db | Standard Deviation 3 |
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 18 Months Compared to Baseline | -3.1 db | Standard Deviation 2.9 |
95% CI: [-9.4, 2.4]
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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 24 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 24 months. Higher macular sensitivity (higher db) is better.
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. One participant in the minocycline group was excluded because their Month 24 data was not recorded due to withdrawal from the study prior to the Month 24 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 24 Months Compared to Baseline | 0.1 db | Standard Deviation 3.2 |
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 24 Months Compared to Baseline | -3.7 db | Standard Deviation 3.5 |
95% CI: [-9.5, 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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 3 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 3 months. Higher macular sensitivity (higher db) is better.
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 3 Months Compared to Baseline | 0.5 db | Standard Deviation 1.2 |
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 3 Months Compared to Baseline | -0.4 db | Standard Deviation 2.5 |
95% CI: [-3.9, 2.3]
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 difference between the minocycline and placebo groups in the change in macular sensitivity as measured by microperimetry in the study eye at 6 months compared to baseline. Values presented represent mean and standard deviation of change from baseline at 6 months. Higher macular sensitivity (higher db) is better.
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 6 Months Compared to Baseline | 0.7 db | Standard Deviation 1.3 |
| Minocycline | Changes in Mean Macular Sensitivity in the Study Eye as Measured by Microperimetry at 6 Months Compared to Baseline | -1.5 db | Standard Deviation 1.7 |
95% CI: [-4.5, 0.3]
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 difference between the minocycline and placebo groups in the 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 because their Month 12 data was not recorded due to withdrawal from the study prior to the Month 12 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline | -99.3 micrometers | Standard Deviation 45 |
| Minocycline | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 12 Months Compared to Baseline | -144.8 micrometers | Standard Deviation 303.7 |
95% CI: [-522.6, 431.6]
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 mean difference between the minocycline and placebo groups in the 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. One participant in the minocycline group was excluded because their Month 18 data was not recorded due to withdrawal from the study prior to the Month 18 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 18 Months Compared to Baseline | -111.8 micrometers | Standard Deviation 63.9 |
| Minocycline | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 18 Months Compared to Baseline | -124.5 micrometers | Standard Deviation 321.3 |
95% CI: [-513.1, 487.6]
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 difference between the minocycline and placebo groups in the 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. One participant in the minocycline group was excluded because their Month 24 data was not recorded due to withdrawal from the study prior to the Month 24 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 24 Months Compared to Baseline | -125.8 micrometers | Standard Deviation 63.4 |
| Minocycline | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 24 Months Compared to Baseline | -135.3 micrometers | Standard Deviation 307 |
95% CI: [-487, 468]
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 difference between the minocycline and placebo groups in the 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 6 Months Compared to Baseline | -91.0 micrometers | Standard Deviation 53.8 |
| Minocycline | Changes in Retinal Thickness in the Study Eye as Measured by Optical Coherence Tomography (OCT) at 6 Months Compared to Baseline | -142.8 micrometers | Standard Deviation 146.5 |
95% CI: [-231.2, 127.6]
Secondary
Mean Change in the ETDRS BCVA in the Study Eye at 24 Months Compared to Baseline
The outcome measure is the mean difference between the minocycline and placebo groups in the 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. One participant in the minocycline group was excluded because their Month 24 data was not recorded due to withdrawal from the study prior to the Month 24 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in the ETDRS BCVA in the Study Eye at 24 Months Compared to Baseline | 2.8 ETDRS letters | Standard Deviation 10.7 |
| Minocycline | Mean Change in the ETDRS BCVA in the Study Eye at 24 Months Compared to Baseline | 8.5 ETDRS letters | Standard Deviation 14.8 |
95% CI: [-17.1, 28.6]
Secondary
Number of Bevacizumab Injections From Baseline to 12 Months
The outcome measure is the difference between the minocycline and placebo groups in 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 |
|---|---|---|---|
| Placebo | Number of Bevacizumab Injections From Baseline to 12 Months | 5.5 bevacizumab injections | Standard Deviation 1.9 |
| Minocycline | Number of Bevacizumab Injections From Baseline to 12 Months | 6.6 bevacizumab injections | Standard Deviation 2.4 |
Secondary
Number of Bevacizumab Injections From Baseline to 24 Months
The outcome measure is the difference between the minocycline and placebo groups in 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 |
|---|---|---|---|
| Placebo | Number of Bevacizumab Injections From Baseline to 24 Months | 9.0 bevacizumab injections | Standard Deviation 5.9 |
| Minocycline | Number of Bevacizumab Injections From Baseline to 24 Months | 8.8 bevacizumab injections | Standard Deviation 4.2 |
Comparison: The mean difference between the minocycline and placebo treatment arms in number of bevacizumab injections received from baseline to Month 24 is reported.
Secondary
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 outcome measure is the difference between the between the minocycline and placebo groups in 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. One participant in the minocycline group was excluded because their Month 12 data was not recorded due to withdrawal from the study prior to the Month 12 visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | Decrease | 4 participants |
| Placebo | 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 | Increase | 0 participants |
| Placebo | 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 | No Change | 0 participants |
| Minocycline | 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 | Decrease | 2 participants |
| Minocycline | 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 | Increase | 0 participants |
| Minocycline | 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 | No Change | 2 participants |
Secondary
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 outcome measure is the difference between the between the minocycline and placebo groups in 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. One participant in the minocycline group was excluded because their Month 24 data was not recorded due to withdrawal from the study prior to the Month 24 visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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. | Decrease | 4 participants |
| Placebo | 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. | Increase | 0 participants |
| Placebo | 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. | No Change | 0 participants |
| Minocycline | 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. | Increase | 1 participants |
| Minocycline | 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. | Decrease | 3 participants |
| Minocycline | 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. | No Change | 0 participants |
Secondary
Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline
The outcome measure is the difference between the minocycline and placebo groups in the number of participants experiencing an improvement of ≥ 1 logOCT scale step from baseline to Month 12. Improvement in ≥ 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 because their Month 12 data was not recorded due to withdrawal from the study prior to the Month 12 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline | 2 Participants |
| Minocycline | Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 12 Months Compared to Baseline | 3 Participants |
Secondary
Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline
The outcome measure is the difference between the minocycline and placebo groups in the number of participants experiencing an improvement of ≥ 1 logOCT scale step from baseline to Month 24. Improvement in ≥ 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. One participant in the minocycline group was excluded because their Month 24 data was not recorded due to withdrawal from the study prior to the Month 24 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline | 3 Participants |
| Minocycline | Number of Participants Improving ≥ 1 logOCT Scale Step in the Study Eye at 24 Months Compared to Baseline | 3 Participants |