Trial Outcomes & Findings for Efficacy and Safety of Ranibizumab (Intravitreal Injections) Versus Laser Treatment in Patients With Visual Impairment Due to Diabetic Macular Edema (NCT NCT00901186)

Last Updated: 2017-03-03

Results Overview

Visual acuity (VA) was assessed on the study eye during every study visit using best correction determined from protocol refraction. VA measurements were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

83 participants

Primary outcome timeframe

Baseline, 12 months

Results posted on

2017-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	RFB002 RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Overall Study STARTED	40	43
Overall Study Safety Set	39	43
Overall Study Intent to Treat	35	38
Overall Study COMPLETED	31	32
Overall Study NOT COMPLETED	9	11

Reasons for withdrawal

Reasons for withdrawal
Measure	RFB002 RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Overall Study Lack of Efficacy	0	1
Overall Study Abnormal laboratory values	0	1
Overall Study Lost to Follow-up	2	0
Overall Study Adverse Event	2	4
Overall Study Administration problems	0	1
Overall Study Protocol deviations	5	4

Baseline Characteristics

Efficacy and Safety of Ranibizumab (Intravitreal Injections) Versus Laser Treatment in Patients With Visual Impairment Due to Diabetic Macular Edema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RFB002 n=39 Participants RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation n=43 Participants At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.	Total n=82 Participants Total of all reporting groups
Age, Continuous	61.31 Years STANDARD_DEVIATION 8.94 • n=5 Participants	65.47 Years STANDARD_DEVIATION 9.40 • n=7 Participants	63.49 Years STANDARD_DEVIATION 9.36 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 12 months

Population: Intent-to-treat (ITT): The ITT consisted of all randomized participants who received at least one intravitreal ranibizumab injection of one laser photocoagulation treatment for whom there was at least one baseline and one post-treatment BCVA value. Participants who had both Baseline and Month 12 BCVA values only were included in this analysis.

Outcome measures

Outcome measures
Measure	RFB002 n=32 Participants RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation n=33 Participants At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA)	9.41 letters Standard Deviation 9.15	5.79 letters Standard Deviation 9.40

SECONDARY outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	RFB002 n=35 Participants RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation n=38 Participants At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Percentage of Participants With Improvement in BCVA	74.29 Percentage of participants	68.42 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Population: ITT: The ITT consisted of all randomized participants who received at least one intravitreal ranibizumab injection of one laser photocoagulation treatment for whom there was at least one baseline and one post-treatment BCVA value. For each month, participants who had both the baseline and the study month BCVA values were included in the analysis.

Outcome measures

Outcome measures
Measure	RFB002 n=35 Participants RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation n=38 Participants At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 1 (n=34,38)	4.56 letters Standard Deviation 7.38	1.32 letters Standard Deviation 7.99
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 2 (n=31,38)	4.61 letters Standard Deviation 6.55	1.89 letters Standard Deviation 8.04
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 3 (n=33,38)	6.24 letters Standard Deviation 6.41	3.11 letters Standard Deviation 7.83
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 4 (n=33,37)	6.33 letters Standard Deviation 7.40	2.76 letters Standard Deviation 8.66
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 5 (n=31,37)	7.03 letters Standard Deviation 8.00	3.38 letters Standard Deviation 8.95
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 6 (n=33,35)	7.61 letters Standard Deviation 6.88	4.11 letters Standard Deviation 7.65
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 7 (n=33,33)	7.91 letters Standard Deviation 7.16	3.85 letters Standard Deviation 7.97
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 8 (n=32,34)	8.00 letters Standard Deviation 7.77	3.21 letters Standard Deviation 7.75
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 9 (n=32,33)	8.44 letters Standard Deviation 8.78	6.00 letters Standard Deviation 9.81
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 10 (n=31,32)	7.32 letters Standard Deviation 8.17	5.84 letters Standard Deviation 9.14
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 11 (n=32,32)	7.69 letters Standard Deviation 8.88	6.44 letters Standard Deviation 8.32
Evolution of Mean Change From Baseline in BCVA by Study Visit Month 12 (n=32,33)	9.41 letters Standard Deviation 9.15	5.79 letters Standard Deviation 9.40

SECONDARY outcome

Timeframe: 12 months

VA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters.

Outcome measures

Outcome measures
Measure	RFB002 n=35 Participants RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation n=38 Participants At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Percentage of Participants With VA > 73 Letters With Ranibizumab (0.5 mg) vs Laser.	54.29 Percentage of participants	23.68 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

CRT was assessed by Optical Coherence Tomography (OCT).

Outcome measures

Outcome measures
Measure	RFB002 n=35 Participants RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation n=38 Participants At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 1 (n=33,37)	-50.18 micrometers Standard Deviation 62.23	-21.86 micrometers Standard Deviation 82.86
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 2 (n=31,38)	-69.52 micrometers Standard Deviation 65.10	-14.21 micrometers Standard Deviation 66.95
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 3 (n=33,37)	-80.64 micrometers Standard Deviation 87.06	-43.16 micrometers Standard Deviation 89.74
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 4 (n=33,38)	-81.79 micrometers Standard Deviation 92.14	-37.66 micrometers Standard Deviation 83.29
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 5 (n=30,37)	-77.77 micrometers Standard Deviation 73.47	-28.92 micrometers Standard Deviation 91.51
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 6 (n=33,34)	-93.73 micrometers Standard Deviation 79.42	-40.47 micrometers Standard Deviation 100.12
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 7 (n=33,35)	-92.76 micrometers Standard Deviation 79.55	-60.94 micrometers Standard Deviation 110.05
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 8 (n=32,34)	-92.41 micrometers Standard Deviation 82.27	-64.82 micrometers Standard Deviation 110.05
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 9 (n=32,34)	-81.59 micrometers Standard Deviation 81.38	-74.59 micrometers Standard Deviation 112.75
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 10 (n=31,31)	-83.32 micrometers Standard Deviation 81.56	-84.39 micrometers Standard Deviation 102.79
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 11 (n=32,33)	-98.03 micrometers Standard Deviation 76.75	-94.85 micrometers Standard Deviation 114.67
Mean Change From Baseline in Central Retinal Thickness (CRT) by Study Visit Month 12 (n=32,33)	-76.28 micrometers Standard Deviation 76.56	-86.00 micrometers Standard Deviation 115.53

SECONDARY outcome

Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

CRT was assessed by Optical Coherence Tomography (OCT).

Outcome measures

Outcome measures
Measure	RFB002 n=35 Participants RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation n=38 Participants At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Percentage of CRT Change From Baseline by Study Visit Month 1 (n=33,37)	-12.06 Percentage change Standard Deviation 15.16	-3.01 Percentage change Standard Deviation 17.52
Percentage of CRT Change From Baseline by Study Visit Month 2 (n=31,38)	-15.61 Percentage change Standard Deviation 13.90	-2.20 Percentage change Standard Deviation 15.24
Percentage of CRT Change From Baseline by Study Visit Month 3 (n=33,37)	-18.25 Percentage change Standard Deviation 17.09	-7.97 Percentage change Standard Deviation 17.80
Percentage of CRT Change From Baseline by Study Visit Month 4 (n=33,38)	-18.00 Percentage change Standard Deviation 17.93	-6.99 Percentage change Standard Deviation 17.18
Percentage of CRT Change From Baseline by Study Visit Month 5 (n=30,37)	-18.21 Percentage change Standard Deviation 15.68	-6.39 Percentage change Standard Deviation 19.27
Percentage of CRT Change From Baseline by Study Visit Month 6 (n=33,34)	-20.69 Percentage change Standard Deviation 15.85	-8.55 Percentage change Standard Deviation 21.06
Percentage of CRT Change From Baseline by Study Visit Month 7 (n=33,35)	-21.11 Percentage change Standard Deviation 15.68	-12.50 Percentage change Standard Deviation 23.05
Percentage of CRT Change From Baseline by Study Visit Month 8 (n=32,34)	-21.20 Percentage change Standard Deviation 16.43	-13.02 Percentage change Standard Deviation 20.95
Percentage of CRT Change From Baseline by Study Visit Month 9 (n=32,34)	-19.17 Percentage change Standard Deviation 17.95	-15.68 Percentage change Standard Deviation 21.87
Percentage of CRT Change From Baseline by Study Visit Month 10 (n=31,31)	-19.55 Percentage change Standard Deviation 17.34	-17.24 Percentage change Standard Deviation 19.63
Percentage of CRT Change From Baseline by Study Visit Month 11 (n=32,33)	-22.65 Percentage change Standard Deviation 15.85	-19.04 Percentage change Standard Deviation 22.31
Percentage of CRT Change From Baseline by Study Visit Month 12 (n=32,33)	-18.23 Percentage change Standard Deviation 16.66	-16.59 Percentage change Standard Deviation 25.06

Adverse Events

RFB002

Serious events: 3 serious events

Other events: 2 other events

Deaths: 0 deaths

Laser Photocoagulation

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RFB002 n=39 participants at risk RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation n=43 participants at risk At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Cardiac disorders Cardiac failure acute	2.6% 1/39	0.00% 0/43
Cardiac disorders Cardiac failure congestive	0.00% 0/39	2.3% 1/43
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Penile cancer	0.00% 0/39	2.3% 1/43
Nervous system disorders Cerebral infarction	2.6% 1/39	0.00% 0/43
Vascular disorders Necrosis ischaemic	2.6% 1/39	0.00% 0/43

Other adverse events

Other adverse events
Measure	RFB002 n=39 participants at risk RFB002 0.5 mg was administered to the study eye with a single monthly intravitreal injection on day 1, day 30 and day 60. After day 90, if stable vision was not achieved, a monthly injection of RFB002 0.5 mg was administered until stable vision was achieved.	Laser Photocoagulation n=43 participants at risk At least one treatment of laser photocoagulation was applied on day 1. The maximum number of laser photocoagulation treatments was 4.
Infections and infestations Pharyngitis	5.1% 2/39	0.00% 0/43
Surgical and medical procedures Cataract operation	0.00% 0/39	7.0% 3/43

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 1-862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER