Trial Outcomes & Findings for Safety and Efficacy of a New Treatment as Adjunctive Therapy to Anti-vascular Endothelial Growth Factor (Anti-VEGF) Treatment in Patients With Age-Related Macular Degeneration (AMD) (NCT NCT00511706)

Last Updated: 2019-04-25

Results Overview

The injection free interval was defined as the number of days between receiving the second ranibizumab injection (day 7 to 14) to the investigator's determination of eligibility to receive a third ranibizumab injection in the study eye.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

243 participants

Primary outcome timeframe

Week 1 to Week 25

Results posted on

2019-04-25

Participant Flow

Participant milestones

Participant milestones
Measure	Dexamethasone and Ranibizumab Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham and Ranibizumab Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Overall Study STARTED	123	120
Overall Study COMPLETED	115	115
Overall Study NOT COMPLETED	8	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of a New Treatment as Adjunctive Therapy to Anti-vascular Endothelial Growth Factor (Anti-VEGF) Treatment in Patients With Age-Related Macular Degeneration (AMD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dexamethasone and Ranibizumab n=123 Participants Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham and Ranibizumab n=120 Participants Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.	Total n=243 Participants Total of all reporting groups
Age, Continuous	76.1 Years STANDARD_DEVIATION 8.83 • n=5 Participants	76.2 Years STANDARD_DEVIATION 8.50 • n=7 Participants	76.1 Years STANDARD_DEVIATION 8.65 • n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	69 Participants n=7 Participants	145 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	51 Participants n=7 Participants	98 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 1 to Week 25

Population: Intent-to-treat population consisted of all randomized patients.

Outcome measures

Outcome measures
Measure	Dexamethasone and Ranibizumab n=123 Participants Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham and Ranibizumab n=120 Participants Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Injection Free Interval	34 Days Interval 28.0 to 85.0	29 Days Interval 28.0 to 56.0

SECONDARY outcome

Timeframe: Baseline, Week 25

Population: Participants from the Intent-to-treat population (all randomized patients) with data available at Baseline and Week 25 for analyses.

BCVA is measured using an eye chart and is reported as the number of letters read correctly (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

Outcome measures
Measure	Dexamethasone and Ranibizumab n=122 Participants Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham and Ranibizumab n=120 Participants Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25 Baseline	55.5 Letters Standard Deviation 15.27	58.1 Letters Standard Deviation 12.64
Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25 Change from baseline at week 25	2.0 Letters Standard Deviation 8.61	2.4 Letters Standard Deviation 9.14

SECONDARY outcome

Timeframe: Baseline, Week 25

Population: Participants from the Intent-to-treat population (all randomized patients) with data available at Baseline and Week 25 for analyses.

Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina, was performed in the study eye after pupil dilation at baseline and Month 25.

Outcome measures

Outcome measures
Measure	Dexamethasone and Ranibizumab n=120 Participants Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham and Ranibizumab n=119 Participants Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye Baseline	260.28 Microns Standard Deviation 123.625	272.45 Microns Standard Deviation 130.829
Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye Change from baseline at week 25 (n=105, 111)	-7.12 Microns Standard Deviation 77.898	-13.00 Microns Standard Deviation 97.651

SECONDARY outcome

Timeframe: Screening (-Week 28), Week 25

Population: Participants from the intent-to-treat population (all randomized participants) with data available at Screening and Week 25 for analyses.

Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the study eye after dilation at Screening and Week 25.

Outcome measures

Outcome measures
Measure	Dexamethasone and Ranibizumab n=118 Participants Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham and Ranibizumab n=116 Participants Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye Screening	8.44 Millimeters square (MM^2) Standard Deviation 6.863	8.12 Millimeters square (MM^2) Standard Deviation 6.359
Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye Change from Screening at Week 25 (n= 95,99)	-2.32 Millimeters square (MM^2) Standard Deviation 4.927	-1.73 Millimeters square (MM^2) Standard Deviation 5.465

Adverse Events

Dexamethasone and Ranibizumab

Serious events: 9 serious events

Other events: 86 other events

Deaths: 0 deaths

Sham and Ranibizumab

Serious events: 14 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Dexamethasone and Ranibizumab n=121 participants at risk Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham and Ranibizumab n=118 participants at risk Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Eye disorders Conjunctival haemorrhage	19.0% 23/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	10.2% 12/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Eye disorders Intraocular pressure increased	13.2% 16/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	4.2% 5/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Eye disorders Retinal haemorrhage	7.4% 9/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	5.9% 7/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Eye disorders Visual acuity reduced	7.4% 9/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	4.2% 5/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Eye disorders Macular degeneration	5.0% 6/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	4.2% 5/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Eye disorders Vitreous floaters	5.0% 6/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	1.7% 2/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Eye disorders Cataract subcapsular	5.0% 6/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Eye disorders Eye pain	4.1% 5/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	6.8% 8/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Eye disorders Cataract	3.3% 4/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	5.9% 7/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Eye disorders Vitreous detachment	1.7% 2/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	5.9% 7/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.

Additional Information

Therapeutic Area Head,

Allergan, Inc

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	Dexamethasone and Ranibizumab n=121 participants at risk Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham and Ranibizumab n=118 participants at risk Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Renal and urinary disorders Renal failure	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	1.7% 2/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Injury, poisoning and procedural complications Therapeutic agent toxicity	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Infections and infestations Pneumonia	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	2.5% 3/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Cardiac disorders Myocardial infarction	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	1.7% 2/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Metabolism and nutrition disorders Hyponatraemia	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Infections and infestations Gastroenteritis	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Injury, poisoning and procedural complications Spinal compression fracture	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Nervous system disorders Stupor	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Infections and infestations Enterococcal infection	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Metabolism and nutrition disorders Failure to thrive	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Gastrointestinal disorders Small intestinal obstruction	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Cardiac disorders Bradycardia	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Gastrointestinal disorders Pancreatitis acute	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
General disorders Non-cardiac chest pain	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	1.7% 2/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
General disorders Hernia	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Cardiac disorders Cardiac failure chronic	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Cardiac disorders Ischaemic cardiomyopathy	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Cardiac disorders Mitral valve incompetence	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Infections and infestations Appendicitis	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Cardiac disorders Atrioventricular block complete	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	1.7% 2/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Infections and infestations Escherichia bacteraemia	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Nervous system disorders Cerebrovascular accident	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Infections and infestations Respiratory tract infection	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Hepatobiliary disorders Cholecystitis	0.83% 1/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.00% 0/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Gastrointestinal disorders Duodenal ulcer perforation	0.00% 0/121 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.	0.85% 1/118 Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.