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| Name | Class |
|---|---|
| Bayer | INDUSTRY |
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The primary objective of the study was to compare the efficacy of intravitreal (IVT)-administered REGN910-3 compared to intravitreal aflibercept injection (IAI) in improving best corrected visual acuity (BCVA) in participants with diabetic macular edema (DME).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| REGN910-3 (3 mg: 2 mg) | Experimental | Participants were administered intravitreal injection of REGN910-3 (3 milligram (mg):2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 up to Week 32. |
|
| REGN910-3 (6 mg:2 mg) | Experimental | Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to week 12. |
|
| Aflibercept 2 mg | Active Comparator | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. |
|
| REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8 | Experimental | Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 16 and Q8 through Week 32. |
|
| REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12 | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| REGN910-3 | Drug | Co-formulation for intravitreal (IVT) injection consisting of REGN910 (nesvacumab) and REGN3 (aflibercept) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12 | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. Best Corrected Visual Acuity (BCVA) score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 12. | Baseline, Week 12 |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 36. | Baseline, Week 36 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12 | Central Sub-field Retinal Thickness (CST) was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Other inclusion/ exclusion criteria apply
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trial Management | Regeneron Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mesa | Arizona | United States | ||||
Out of 438 participants, 302 were randomized & treated in study. Participants were randomized in 1:2:3 to receive REGN910-3 3:2mg, REGN910-3 6:2mg & 2mg intravitreal aflibercept injection followed by re-randomization at week 12 in REGN910-3 6:2mg & IAI 2mg arm. Not all participants who completed Week 12 were re-randomized & continued to Week 36.
The study was conducted at 70 sites in US. A total of 438 participants were screened in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | REGN910-3 (3 mg: 2 mg) | Participants were administered intravitreal injection of REGN910-3 (3 milligram [mg]:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 up to Week 32. |
| FG001 | REGN910-3 (6 mg:2 mg) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Baseline (Day 1) up to Week 12 |
|
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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 31, 2017 | Jul 10, 2018 |
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Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 20 and Q12 through Week 32.
|
| Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8 | Experimental | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week16 and Q8 through Week 32. |
|
| Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12 | Experimental | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week 20 and Q12 through Week 32. |
|
| Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Experimental | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 and Q8 through week 32. |
|
| Intravitreal Aflibercept Injection (IAI) | Drug |
|
|
| Baseline, Week 12 |
| Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 36. | Baseline, Week 36 |
| Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative). | Baseline, Week 12 |
| Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative). | Baseline, Week 36 |
| Tucson |
| Arizona |
| United States |
| Arcadia | California | United States |
| Beverly Hills | California | United States |
| Mountain View | California | United States |
| Oceanside | California | United States |
| Palm Desert | California | United States |
| Colorado Springs | Colorado | United States |
| New London | Connecticut | United States |
| Lakeland | Florida | United States |
| Tampa | Florida | United States |
| Winter Haven | Florida | United States |
| Augusta | Georgia | United States |
| Decatur | Georgia | United States |
| ‘Aiea | Hawaii | United States |
| Chicago | Illinois | United States |
| New Albany | Indiana | United States |
| Shawnee Mission | Kansas | United States |
| Lexington | Kentucky | United States |
| Portland | Maine | United States |
| Baltimore | Maryland | United States |
| Rockville | Maryland | United States |
| Boston | Massachusetts | United States |
| Grand Rapids | Michigan | United States |
| Jackson | Michigan | United States |
| Minneapolis | Minnesota | United States |
| Florissant | Missouri | United States |
| Las Vegas | Nevada | United States |
| Bloomfield | New Jersey | United States |
| Edison | New Jersey | United States |
| Teaneck | New Jersey | United States |
| Albany | New York | United States |
| Rochester | New York | United States |
| Asheville | North Carolina | United States |
| Charlotte | North Carolina | United States |
| Kingston | Pennsylvania | United States |
| Florence | South Carolina | United States |
| West Columbia | South Carolina | United States |
| Rapid City | South Dakota | United States |
| Germantown | Tennessee | United States |
| Nashville | Tennessee | United States |
| Abilene | Texas | United States |
| Austin | Texas | United States |
| Dallas | Texas | United States |
| Fort Worth | Texas | United States |
| Harlingen | Texas | United States |
| Houston | Texas | United States |
| San Antonio | Texas | United States |
| The Woodlands | Texas | United States |
| Willow Park | Texas | United States |
| Bellevue | Washington | United States |
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to week 12. |
| FG002 | Aflibercept 2 mg | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. |
| FG003 | REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8 | Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, week 4 and week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 and Q8 through week 32. |
| FG004 | REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12 | Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 20 and Q12 through Week 32. |
| FG005 | Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive IAI at week 16 and Q8 through week 32. |
| FG006 | Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week 20 and Q12 through Week 32. |
| FG007 | Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 and Q8 through week 32. |
| COMPLETED |
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| NOT COMPLETED |
|
|
| From Week 12 up to Week 36 |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | REGN910-3 (3 mg: 2 mg) | Participants were administered intravitreal injection of REGN910-3 (3 milligram (mg):2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 up to Week 32 |
| BG001 | REGN910-3 (6 mg:2 mg) | Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, week 4 and week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 or Week 20 and Q8 or Q12 through week 32. |
| BG002 | Aflibercept 2 mg | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive IAI or REGN910-3 (6 mg:2 mg) at week 16 or 20 and Q8 through week 32. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | 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 | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12 | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. Best Corrected Visual Acuity (BCVA) score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 12. | Full analysis set included all randomized participants who received any study drug, had baseline measurement of BCVA & at least 1 post-baseline assessment of BCVA. Last observation carried forward (LOCF) method was used to impute missing data. Here "Overall Number of Participants Analyzed" = Participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Letters correctly read | Baseline, Week 12 |
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| Primary | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 36. | FAS secondary randomization set = all participants in full analysis set (FAS) who had completed study through week 12, received any study drug after secondary randomization or after Week 12, had BCVA assessment at Week 12 & had at least 1 post-Week 16 BCVA assessment. Overall Number of Participants Analyzed=Participants evaluable for this endpoint. | Posted | Mean | Standard Deviation | Letters correctly read | Baseline, Week 36 |
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| Secondary | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12 | Central Sub-field Retinal Thickness (CST) was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12. | Full analysis set included all randomized participants who received any study drug, had baseline measurement of BCVA & at least 1 post-baseline assessment of BCVA. Last observation carried forward (LOCF) method was used to impute missing data. Here "Overall Number of Participants Analyzed" = Participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Microns | Baseline, Week 12 |
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| Secondary | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 36. | FAS secondary randomization set was used. Here "Overall Number of Participants Analyzed"= Participants who were evaluable for this endpoint. | Posted | Mean | Standard Deviation | Microns | Baseline, Week 36 |
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| Secondary | Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative). | Full analysis set included all randomized participants who received any study drug, had baseline measurement of BCVA & at least 1 post-baseline assessment of BCVA. Last observation carried forward (LOCF) method was used to impute missing data. Here "Overall Number of Participants Analyzed" = Participants who were evaluable for this outcome measure. | Posted | Number | Percentage of participants | Baseline, Week 12 |
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| Secondary | Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative). | FAS secondary randomization set was used. Overall Number of Participants Analyzed = Participants who were evaluable for this outcome measure. | Posted | Number | Percentage of participants | Baseline, Week 36 |
|
All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 36) regardless of seriousness or relationship to investigational product.
Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (Baseline up to Week 36).
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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 | REGN910-3 (3 mg: 2 mg) | Participants were administered intravitreal injection of REGN910-3 (3 milligram (mg):2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 up to Week 32. | 5 | 50 | 6 | 50 | 18 | 50 |
| EG001 | REGN910-3 (6 mg:2 mg) | Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, week 4 and week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 or Week 20 and Q8 or Q12 through week 32. | 0 | 100 | 18 | 100 | 42 | 100 |
| EG002 | Aflibercept 2 mg | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive IAI or REGN910-3 (6 mg:2 mg) at week 16 or 20 and Q8 through week 32. | 4 | 152 | 31 | 152 | 55 | 152 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiomegaly | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiorenal syndrome | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Iridocyclitis | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Retinal artery occlusion | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Intestinal varices | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Death | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Diabetic foot infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Endocarditis staphylococcal | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Extradural abscess | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Gangrene | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Gastric infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Septic arthritis staphylococcal | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Burns second degree | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Burns third degree | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Mental status changes postoperative | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Troponin increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Lactic acidosis | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Type 1 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Breast cancer stage ii | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Intraductal proliferative breast lesion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Large intestine benign neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Guillain-Barre syndrome | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hepatic encephalopathy | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| End stage renal disease | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Nephrotic syndrome | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Penile oedema | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Respiratory depression | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Diabetic foot | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Arteriosclerosis | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypertensive emergency | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Peripheral arterial occlusive disease | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctival haemorrhage | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Vitreous detachment | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Management | Regeneron Pharmaceuticals, Inc. | 844-734-6643 | clinicaltrials@regeneron.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 12, 2017 | Jul 10, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| C533178 | aflibercept |
| D007267 | Injections |
| ID | Term |
|---|---|
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
| Death |
|
| Lost to Follow-up |
|
| Physician Decision |
|
| Withdrawal by Subject |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors. |
| ANCOVA |
| 0.9716 |
Threshold for significance at 0.05 level. |
| Least square mean difference |
| 0.04 |
| 2-Sided |
| 95 |
| - 2.10 |
| 2.18 |
| Superiority |
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, week 4 and week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 and Q8 through week 32. |
| OG002 | REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12 | Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 20 and Q12 through Week 32. |
| OG003 | Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive IAI at week 16 and Q8 through week 32. |
| OG004 | Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week 20 and Q12 through Week 32. |
| OG005 | Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 and Q8 through week 32. |
|
|
|
| OG002 | Aflibercept 2 mg | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive IAI or REGN910-3 (6 mg:2 mg) at week 16 or 20 and Q8 through week 32. |
|
|
|
| REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12 |
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 20 and Q12 through Week 32. |
| OG003 | Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive IAI at week 16 and Q8 through week 32. |
| OG004 | Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week 20 and Q12 through Week 32. |
| OG005 | Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 and Q8 through week 32. |
|
|
|
| OG002 |
| Aflibercept 2 mg |
Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive IAI or REGN910-3 (6 mg:2 mg) at week 16 or 20 and Q8 through week 32. |
|
|
|
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 20 and Q12 through Week 32.
| OG003 | Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive IAI at week 16 and Q8 through week 32. |
| OG004 | Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week 20 and Q12 through Week 32. |
| OG005 | Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 and Q8 through week 32. |
|
|
|