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| ID | Type | Description | Link |
|---|---|---|---|
| 11-EI-0263 |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants injected with bevacizumab for three months followed by PRN dosing and placebo twice daily for 24 months |
|
| Minocycline | Experimental | Participants injected with bevacizumab for three months followed by PRN dosing and 100mg minocycline twice daily for 24 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minocycline | Drug | 100 mg of minocycline in a pink opaque capsule |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to Month 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to Month 12 |
| Number of Bevacizumab Injections From Baseline to 24 Months |
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PARTICIPANT ELIGIBILITY CRITERIA
INCLUSION CRITERIA:
To be eligible, the following 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.
Female participants of childbearing potential and male participants able to father children must meet the following site-specific criteria:
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:
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:
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.
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 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.
EXCLUSION CRITERIA:
A participant is not eligible if any of the following exclusion criteria are present:
Participant is in another investigational study and actively receiving investigational product for BRVO.
Participant is unable to comply with study procedures or follow-up visits.
Participant has a known hypersensitivity to sodium fluorescein dye.
Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).
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 an allergy or hypersensitivity to minocycline or any drug in the tetracycline family.
Participant is currently taking a tetracycline medication.
Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane.
Participant has a blood pressure of greater than 180/110 (systolic above 180 OR diastolic above 110).
a. If blood pressure is brought below 180/110 by anti-hypertensive treatment, the participant can become eligible.
Participant is currently being treated with systemic anti-VEGF agents or systemic steroids.
Participant had a cerebral vascular event (CVA) or myocardial infarction (MI) within three months prior to study entry.
Participant has a history of thyroid cancer.
STUDY EYE ELIGIBILITY CRITERIA:
The participant must have at least one eye meeting all inclusion criteria and none of the exclusion criteria listed below:
STUDY EYE INCLUSION CRITERIA
STUDY EYE EXCLUSION CRITERIA
The study eye has macular edema considered to be due to a cause other than BRVO.
An eye should not be considered eligible if:
STUDY EYE SELECTION CRITERIA IN CASES OF BILATERAL DISEASE
If both eyes of a participant meet the criteria, the study eye will be determined at the investigator's discretion.
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| Name | Affiliation | Role |
|---|---|---|
| Catherine A Cukras, M.D. | National Eye Institute (NEI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States | ||
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| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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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.
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Study eye is the unit of analysis and is chosen based on study eye inclusion/exclusion criteria. If both eyes of a participant meet the criteria, the study eye will be determined at the investigator's discretion.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Minocycline |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | ETDRS letters | Baseline to Month 12 |
|
24 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Retinal vein occlusion | Eye disorders | MedDRA (24.0) | Systematic Assessment | CRVO OS |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Catherine Cukras, MD, PhD, Principal Investigator, NEI | National Institutes of Health | 301-435-5061 | cukrasc@nei.nih.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 6, 2021 | Oct 12, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 18, 2021 | Oct 12, 2021 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 9, 2019 | Oct 12, 2021 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D012170 | Retinal Vein Occlusion |
| C562573 | cyclopia sequence |
| D008269 | Macular Edema |
| ID | Term |
|---|---|
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D020246 | Venous Thrombosis |
| D013927 | Thrombosis |
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| ID | Term |
|---|---|
| D008911 | Minocycline |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Placebo |
| Other |
Pill with inactive ingredients in a pink opaque capsule |
|
| Bevacizumab | Drug | 1.25 mg bevacizumab injection |
|
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. |
| Baseline to Month 24 |
| 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. | Baseline to Month 3 |
| 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. | Baseline to Month 6 |
| 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. | Baseline to Month 12 |
| 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. | Baseline to Month 18 |
| 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. | Baseline to Month 24 |
| 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. | Baseline to Month 24 |
| 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. | Baseline to Month 6 |
| 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. | Baseline to Month 12 |
| 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. | Baseline to Month 18 |
| 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. | Baseline to Month 24 |
| 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. | Baseline to Month 12 |
| 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. | Baseline to Month 24 |
| 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. | Baseline to Month 12 |
| 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. | Baseline to Month 24 |
| Bristol Eye Hospital |
| Bristol |
| United Kingdom |
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
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG001 | 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 |
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| 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. | The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. | Posted | Mean | Standard Deviation | bevacizumab injections | Baseline to Month 12 |
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| 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. | The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. | Posted | Mean | Standard Deviation | bevacizumab injections | Baseline to Month 24 |
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| 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. | The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. | Posted | Mean | Standard Deviation | db | Baseline to Month 3 |
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| 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. | The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. | Posted | Mean | Standard Deviation | db | Baseline to Month 6 |
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| 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. | 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. | Posted | Mean | Standard Deviation | db | Baseline to Month 12 |
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| 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. | 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. | Posted | Mean | Standard Deviation | db | Baseline to Month 18 |
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| 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. | 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. | Posted | Mean | Standard Deviation | db | Baseline to Month 24 |
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| 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. | 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. | Posted | Mean | Standard Deviation | ETDRS letters | Baseline to Month 24 |
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| 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. | The secondary outcomes are based on the safety population, which includes all participants who were exposed to IP, regardless of adherence to protocol. | Posted | Mean | Standard Deviation | micrometers | Baseline to Month 6 |
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| 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. | 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. | Posted | Mean | Standard Deviation | micrometers | Baseline to Month 12 |
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| 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. | 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. | Posted | Mean | Standard Deviation | micrometers | Baseline to Month 18 |
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| 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. | 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. | Posted | Mean | Standard Deviation | micrometers | Baseline to Month 24 |
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| 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. | 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. | Posted | Count of Participants | Participants | Baseline to Month 12 |
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| 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. | 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. | Posted | Count of Participants | Participants | Baseline to Month 24 |
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| 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. | 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. | Posted | Number | participants | Baseline to Month 12 |
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| 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. | 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. | Posted | Number | participants | Baseline to Month 24 |
|
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 4 |
| 4 |
| EG001 | 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 | 0 | 5 | 1 | 5 | 5 | 5 |
| Abdominal distension | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Oral mucosal discolouration | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Mastitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Ocular discomfort | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Blood thyroid stimulating hormone increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Renal function test abnormal | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Thyroid function test abnormal | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Nail discolouration | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Skin mass | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Adverse drug reaction | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.0) | Systematic Assessment |
|
| Hyperaemia | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| Retinal pigmentation | Eye disorders | MedDRA (24.0) | Systematic Assessment | Natural progression of disease |
|
| Retinal vein occlusion | Eye disorders | MedDRA (24.0) | Systematic Assessment | Natural progression of disease |
|
Not provided
Not provided
Not provided
| D016769 |
| Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D008268 | Macular Degeneration |
| D012162 | Retinal Degeneration |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| No Change |
|
| Difference in Number of Participants |
| 0 |
| 2-Sided |
Difference = Minocycline - Placebo |
| Other |
The difference between the minocycline and treatment arms in the number of participants experiencing an increase in fluid leakage at Month 12 compared to baseline is reported. |
| Difference in Number of Participants | 2 | 2-Sided | Difference = Minocycline - Placebo | Other | The difference between the minocycline and treatment arms in the number of participants experiencing no change in fluid leakage at Month 12 compared to baseline is reported. |
| No Change |
|
| Difference in Number of Participants |
| 1 |
| 2-Sided |
Difference = Minocycline - Placebo |
| Other |
The difference between the minocycline and treatment arms in the number of participants experiencing an increase in fluid leakage at Month 24 compared to baseline is reported. |
| Difference in Number of Participants | 0 | 2-Sided | Difference = Minocycline - Placebo | Other | The difference between the minocycline and treatment arms in the number of participants experiencing no change in fluid leakage at Month 24 compared to baseline is reported. |