Trial Outcomes & Findings for A Study of Intravitreal Injections of 2.0mg Ranibizumab in Subjects With Chronic Fluid On OCT Post Multiple Injections With Ranibizumab (Super-dose Anti-VEgf SAVE Trial) (NCT NCT01025232)
NCT ID: NCT01025232
Last Updated: 2017-01-02
Results Overview
Early Treatment Diabetic Retinopathy Study Best Corrected Visual Acuity (ETDRS BCVA) was used to quantify visual acuity. BCVA is measured using an eye chart and is reported as the number of letters read correctly 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.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
88 participants
Primary outcome timeframe
1 Year
Results posted on
2017-01-02
Participant Flow
Participant milestones
| Measure |
4 Week Re-treatment
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Overall Study
STARTED
|
46
|
42
|
|
Overall Study
COMPLETED
|
43
|
36
|
|
Overall Study
NOT COMPLETED
|
3
|
6
|
Reasons for withdrawal
| Measure |
4 Week Re-treatment
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Overall Study
Study drug no longer available
|
3
|
6
|
Baseline Characteristics
A Study of Intravitreal Injections of 2.0mg Ranibizumab in Subjects With Chronic Fluid On OCT Post Multiple Injections With Ranibizumab (Super-dose Anti-VEgf SAVE Trial)
Baseline characteristics by cohort
| Measure |
4 Week Re-treatment
n=46 Participants
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
n=42 Participants
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
44 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
83 Participants
n=5 Participants
|
|
Age, Continuous
|
76 years
n=5 Participants
|
77 years
n=7 Participants
|
76.1 years
n=5 Participants
|
|
Gender
Female
|
25 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Gender
Male
|
21 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
46 participants
n=5 Participants
|
42 participants
n=7 Participants
|
88 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 YearEarly Treatment Diabetic Retinopathy Study Best Corrected Visual Acuity (ETDRS BCVA) was used to quantify visual acuity. BCVA is measured using an eye chart and is reported as the number of letters read correctly 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.
Outcome measures
| Measure |
4 Week Re-treatment
n=43 Participants
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
n=36 Participants
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Mean Change From Baseline in ETDRS BCVA at Month 12 (Fixed Interval Dosing Primary Endpoint After 3 Monthly Doses. Variable Interval Dosing Primary Endpoint at 1 Year.)
|
4.1 ETDRS BCVA Letters
Standard Error 1.4
|
4.1 ETDRS BCVA Letters
Standard Error 1.0
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
4 Week Re-treatment
n=46 Participants
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
n=42 Participants
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Evaluate the Incidence and Severity of Ocular and Non-ocular Adverse Events (AEs) Through Month 12
Ocular Events
|
18 Incidents
|
8 Incidents
|
|
Evaluate the Incidence and Severity of Ocular and Non-ocular Adverse Events (AEs) Through Month 12
Serious Non-Ocular Events
|
7 Incidents
|
10 Incidents
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
4 Week Re-treatment
n=46 Participants
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
n=42 Participants
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Determine Number of Patients Who Experience a Loss of 15 or More Letters From Baseline to Month 12 and Month 12 in ETDRS BCVA
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
4 Week Re-treatment
n=46 Participants
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
n=42 Participants
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Determine Number of Patients Who Experience a Gain of 15 or More Letters From Baseline to Month 12 in ETDRS BCVA.
|
5 participants
|
3 participants
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
4 Week Re-treatment
n=46 Participants
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
n=42 Participants
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Evaluate Mean Change in Central Retinal Thickness Over Time Through Month12 as Assessed by All Three OCTs (Stratus, Cirrus, and Spectralis)
|
-59.2 micrometer
Standard Deviation 107.8
|
-31.8 micrometer
Standard Deviation 87.2
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
4 Week Re-treatment
n=46 Participants
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
n=42 Participants
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Assess Number of Ranibizumab Injections in Each of the Two Doses Required Through Month 12
|
11.6 number of injection
Standard Deviation 1.1
|
8.6 number of injection
Standard Deviation 0.8
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Given lack of clinical benefit of 2.0 mg ranibizumab, as demonstrated in the HARBOR trial \[Busbee BG, et al. (2013) Ophthalmology 120(5), 1046-1056\], further secondary analyses were suspended.
Outcome measures
Outcome data not reported
Adverse Events
4 Week Re-treatment
Serious events: 7 serious events
Other events: 18 other events
Deaths: 0 deaths
6 Week Re-treatment
Serious events: 10 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
4 Week Re-treatment
n=46 participants at risk
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
n=42 participants at risk
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Cardiac disorders
Death
|
2.2%
1/46
|
0.00%
0/42
|
|
Cardiac disorders
Myocardial Infarction
|
2.2%
1/46
|
2.4%
1/42
|
|
Cardiac disorders
Arrhythmia
|
2.2%
1/46
|
2.4%
1/42
|
|
Blood and lymphatic system disorders
Idiopathic internal bleeding
|
0.00%
0/46
|
2.4%
1/42
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
2.2%
1/46
|
4.8%
2/42
|
|
Hepatobiliary disorders
Pancreatic cancer
|
2.2%
1/46
|
4.8%
2/42
|
|
Respiratory, thoracic and mediastinal disorders
Lung cancer
|
0.00%
0/46
|
2.4%
1/42
|
|
Musculoskeletal and connective tissue disorders
Hip fracture
|
2.2%
1/46
|
4.8%
2/42
|
|
Skin and subcutaneous tissue disorders
Cellulitis
|
2.2%
1/46
|
0.00%
0/42
|
Other adverse events
| Measure |
4 Week Re-treatment
n=46 participants at risk
Subjects can receive re-treatment every 4 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
6 Week Re-treatment
n=42 participants at risk
Subjects can receive re-treatment every 6 weeks if there is persistent or recurrent intraretinal, subretinal, or sub-RPE fluid on any OCT modality, or any evidence of hemorrhage on clinical evaluation. Every 6 weeks regimen will test potential longer duration of action of 2.0 mg ranibizumab. Subjects will go no longer than 12 weeks without treatment.
Ranibizumab: Intravitreal Injection of 2.0mg formulation
|
|---|---|---|
|
Eye disorders
RPE rip
|
0.00%
0/46
|
2.4%
1/42
|
|
Eye disorders
Subretinal hemorrhage
|
6.5%
3/46
|
4.8%
2/42
|
|
Eye disorders
Vitreous hemorrhage
|
2.2%
1/46
|
2.4%
1/42
|
|
Eye disorders
Vein occlusion
|
2.2%
1/46
|
0.00%
0/42
|
|
Eye disorders
Increase in NS
|
6.5%
3/46
|
0.00%
0/42
|
|
Eye disorders
Increase in PSC
|
8.7%
4/46
|
0.00%
0/42
|
|
Eye disorders
Cataract surgery
|
6.5%
3/46
|
0.00%
0/42
|
|
Eye disorders
PVD
|
6.5%
3/46
|
9.5%
4/42
|
Additional Information
David M. Brown, MD Director of Clinical Research
Retinal Consultants of Houston
Phone: 713-394-7534
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place