Trial Outcomes & Findings for Efficacy and Safety of Lucentis® Use in Patients With Diabetic Macular Edema Evaluating a Spaced Out Follow-up After Intensive Treatment Phase (NCT NCT02032173)
NCT ID: NCT02032173
Last Updated: 2020-10-22
Results Overview
Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 6 months minus BCVA score at 24 months ≤4 letters) were reported.
TERMINATED
PHASE3
31 participants
Month 6 and 24
2020-10-22
Participant Flow
Participants were recruited from 10 centers across France.
Participant milestones
| Measure |
Ranibizumab
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Overall Study
STARTED
|
31
|
|
Overall Study
Included Population - Main Group
|
31
|
|
Overall Study
Rescue Group
|
1
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
31
|
Reasons for withdrawal
| Measure |
Ranibizumab
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Overall Study
Discontinuation due to sponsor decision
|
31
|
Baseline Characteristics
Efficacy and Safety of Lucentis® Use in Patients With Diabetic Macular Edema Evaluating a Spaced Out Follow-up After Intensive Treatment Phase
Baseline characteristics by cohort
| Measure |
Ranibizumab
n=31 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Age, Continuous
|
64.7 Years
STANDARD_DEVIATION 7.08 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Month 6 and 24Population: Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12
Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 6 months minus BCVA score at 24 months ≤4 letters) were reported.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 11 and 24Population: Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12
Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants with a stable BCVA (BCVA score at 11 months minus BCVA score at 24 months ≤4 letters) was calculated as well as its confidence interval at 95%.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Month 3, 6, 8 and 11Population: Included population with evaluable patients at specific time points.
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥10 letters gains in BCVA (compared to the baseline BCVA \[Day 0\]) value for each visit from Month 3 onwards were reported.
Outcome measures
| Measure |
Ranibizumab
n=21 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters
Month 3
|
8 Participants
|
|
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters
Month 6
|
4 Participants
|
|
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters
Month 8
|
3 Participants
|
|
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥10 Letters
Month 11
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline, Months 3, 6, 8 and 11Population: Included population with evaluable patients at specific time points.
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The number of participants maintaining ≥15 letters gains in BCVA (compared to the baseline BCVA \[Day 0\]) value for each visit from Month 3 onwards were reported.
Outcome measures
| Measure |
Ranibizumab
n=21 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters
Month 3
|
4 Participants
|
|
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters
Month 6
|
3 Participants
|
|
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters
Month 8
|
1 Participants
|
|
Visual Acuity: Number of Participants Keeping a BCVA Score Gain ≥15 Letters
Month 11
|
0 Participants
|
SECONDARY outcome
Timeframe: Months 6, 8 and 11Population: Included population with evaluable patients at specific time points.
Best-Corrected Visual Acuity (BCVA) letters were measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. Number of participants presenting with a ≥15 letter loss in BCVA (compared to the value observed at 6 months) and leading to a treatment change (Rescue Group) for month 8 and 11 were analyzed.
Outcome measures
| Measure |
Ranibizumab
n=5 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Visual Acuity: Number of Participants With a BCVA Loss ≥15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye.
Month 6 to Month 8
|
0 Participants
|
|
Visual Acuity: Number of Participants With a BCVA Loss ≥15 Letters at Months 8 and 11 Compared to Month 6 in the Study Eye.
Month 6 to Month 11
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11Population: Included population with evaluable patients at specific time points.
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value \[Day 0\] over a period of 24 months for patients in the Main Group.
Outcome measures
| Measure |
Ranibizumab
n=31 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Month 1
|
5.45 Letters
Standard Deviation 6.444
|
|
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Month 2
|
5.81 Letters
Standard Deviation 7.328
|
|
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Month 3
|
8.05 Letters
Standard Deviation 6.704
|
|
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Month 4
|
9.94 Letters
Standard Deviation 5.805
|
|
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Month 5
|
9.88 Letters
Standard Deviation 5.290
|
|
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Month 6
|
11.00 Letters
Standard Deviation 8.485
|
|
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Month 8
|
10.40 Letters
Standard Deviation 5.413
|
|
Visual Acuity : Change of BCVA From Baseline in the Study Eye (ETDRS)
Month 11
|
10.00 Letters
Standard Deviation NA
standard deviation not calculated for n=1
|
SECONDARY outcome
Timeframe: Baseline, months 1, 2, 3, 4, 5, 6, 8 and 11Population: Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12
Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) was measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log\[CRT/200\]).
Outcome measures
| Measure |
Ranibizumab
n=31 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Month 1
|
-0.10 log[μm/200]
Standard Deviation 0.117
|
|
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Month 2
|
-0.12 log[μm/200]
Standard Deviation 0.122
|
|
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Month 3
|
-0.13 log[μm/200]
Standard Deviation 0.123
|
|
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Month 4
|
-0.13 log[μm/200]
Standard Deviation 0.104
|
|
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Month 5
|
-0.16 log[μm/200]
Standard Deviation 0.096
|
|
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Month 6
|
-0.15 log[μm/200]
Standard Deviation 0.120
|
|
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Month 8
|
-0.12 log[μm/200]
Standard Deviation 0.062
|
|
Central Retinal Thickness : Change of Log OCT From Baseline in the Study Eye
Month 11
|
-0.13 log[μm/200]
Standard Deviation NA
standard deviation not calculated for n=1
|
SECONDARY outcome
Timeframe: Baseline, Months 3, 6, 8 and 11Population: Included population for subjects entering Rescue Group: No subjects provided evaluable data after switching to the Rescue Group
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement. Best value on the scale 100, worst 0. The mean variation in BCVA was compared to the baseline BCVA value \[Day 0\] over a period of 24 months for patients in the Rescue Group.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Months 3, 6, 8 and 11Population: Included population for subjects entering Rescue Group: No subjects provided evaluable data after switching to the Rescue Group
Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative mean change from baseline indicates an improvement and a positive mean change from baseline indicates a worsening.The absolute variations of the Central Retinal Thickness (CRT) measured using a Spectral Domain-Optical Coherence Tomography (SD-OCT) at each visit. Values were calculated as a log OCT (=log\[CRT/200\]).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline, months 11, 12 and 24Population: Included population: No subjects included as analysis required data at month 24 and trial terminated before any subject reached month 12
The global score obtained on the Visual Function Questionnaire 25 (VFQ 25) was compared from baseline to months 11 and 24 for the Main group and from baseline to months 12 and 24 for the Rescue group.
Outcome measures
Outcome data not reported
Adverse Events
Ranibizumab
Serious adverse events
| Measure |
Ranibizumab
n=31 participants at risk
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
Other adverse events
| Measure |
Ranibizumab
n=31 participants at risk
Intravitreal injection with standard dose of 0.5 mg/0.05mL Pro re nata (PRN)
|
|---|---|
|
Cardiac disorders
Coronary artery stenosis
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Eye disorders
Eye allergy (Both eyes)
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Eye disorders
Halo vision (Study eye)
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Eye disorders
Macular oedema (Contralateral eye)
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Eye disorders
Posterior capsule opacification (Contralateral eye)
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Eye disorders
Vitreous haemorrhage (Study eye)
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
General disorders
Chills
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
General disorders
Oedema peripheral
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
General disorders
Pyrexia
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Infections and infestations
Conjunctivitis (Both eyes)
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Infections and infestations
Conjunctivitis viral (Study eye)
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Infections and infestations
Gastroenteritis
|
9.7%
3/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Infections and infestations
Nasopharyngitis
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Injury, poisoning and procedural complications
Wound
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Nervous system disorders
Paraesthesia
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Renal and urinary disorders
Microalbuminuria
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
3.2%
1/31 • Adverse events (AEs) were collected from the patient screening onwards. However, a safety observation period which started from first injection until 4 weeks after discontinuation - up to 11 months.
|
Additional Information
Study Director
Novartis Pharmaceuticals
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