Trial Outcomes & Findings for Safety and Tolerability of Ranibizumab in Mono/Bilateral Wet Age Related Macular Degeneration (w-AMD) Patients in Eyes With BCVA<2/10 and/or 2nd Affected Eye (NCT NCT01986907)
NCT ID: NCT01986907
Last Updated: 2019-07-19
Results Overview
Monitoring and recording all adverse events, including serious adverse events.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
1049 participants
Primary outcome timeframe
Baseline to Month 12
Results posted on
2019-07-19
Participant Flow
Patients were recruited from investigative sites located in Italy.
This reporting group includes all treated patients (one eye or both eyes)
Participant milestones
| Measure |
Ranibizumab
patients treated with 0.5mg ranibizumab
|
|---|---|
|
Overall Study
STARTED
|
936
|
|
Overall Study
COMPLETED
|
774
|
|
Overall Study
NOT COMPLETED
|
162
|
Reasons for withdrawal
| Measure |
Ranibizumab
patients treated with 0.5mg ranibizumab
|
|---|---|
|
Overall Study
Adverse Event
|
11
|
|
Overall Study
Unsatisfactory therapeutic effect
|
24
|
|
Overall Study
Protocol Violation
|
4
|
|
Overall Study
Withdrawal by Subject
|
76
|
|
Overall Study
Lost to Follow-up
|
38
|
|
Overall Study
Death
|
9
|
Baseline Characteristics
Safety and Tolerability of Ranibizumab in Mono/Bilateral Wet Age Related Macular Degeneration (w-AMD) Patients in Eyes With BCVA<2/10 and/or 2nd Affected Eye
Baseline characteristics by cohort
| Measure |
Ranibizumab
n=936 Participants
patients treated with 0.5mg ranibizumab
|
|---|---|
|
Age, Continuous
|
78.68 years
STANDARD_DEVIATION 7.34 • n=5 Participants
|
|
Age, Customized
18 to less than 65 years
|
33 Participants
n=5 Participants
|
|
Age, Customized
65 to 74 years
|
212 Participants
n=5 Participants
|
|
Age, Customized
75 to 84 years
|
483 Participants
n=5 Participants
|
|
Age, Customized
85 years and older
|
208 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
582 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
354 Participants
n=5 Participants
|
|
Treatment by Eye
Unilateral treatment
|
823 Participants
n=5 Participants
|
|
Treatment by Eye
Bilateral treatment
|
113 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Month 12Population: Safety Set
Monitoring and recording all adverse events, including serious adverse events.
Outcome measures
| Measure |
Ranibizumab
n=936 Participants
patients treated with 0.5mg ranibizumab
|
Unilaterally Treted
|
Bilaterally Treated
|
|---|---|---|---|
|
Number of Participants With Systemic Drug-related Adverse Events
Serious Adverse Event
|
3 participants
|
—
|
—
|
|
Number of Participants With Systemic Drug-related Adverse Events
Non Serious Adverse Event
|
0 participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to Month 12Population: Safety Set
Monitoring and recording all adverse events, including serious adverse events.
Outcome measures
| Measure |
Ranibizumab
n=936 Participants
patients treated with 0.5mg ranibizumab
|
Unilaterally Treted
|
Bilaterally Treated
|
|---|---|---|---|
|
Number of Eyes With Ocular Drug-related Adverse Events
Serious Adverse Event
|
1 eyes
|
—
|
—
|
|
Number of Eyes With Ocular Drug-related Adverse Events
Non Serious Adverse Event
|
8 eyes
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to month 12Population: Safety Set
Outcome measures
| Measure |
Ranibizumab
n=936 Participants
patients treated with 0.5mg ranibizumab
|
Unilaterally Treted
|
Bilaterally Treated
|
|---|---|---|---|
|
Overall Number of Ranibizumab Injections
|
5.97 injections per patient
Standard Deviation 3.62
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to month 12Population: This analysis population includes all eyes naïve to ranibizumab, i.e., had not been treated with the study medication (or with the equivalent commercial formulation) before the first study drug injection, regardless of whether the contralateral eye had been treated.
Mean number of days between two consecutive injections per eye
Outcome measures
| Measure |
Ranibizumab
n=771 eyes
patients treated with 0.5mg ranibizumab
|
Unilaterally Treted
|
Bilaterally Treated
|
|---|---|---|---|
|
Time Interval Between Injections in Bilateral Disease
|
51.94 days
Standard Deviation 26.56
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to month 12Population: Safety set
Number of injections per patient
Outcome measures
| Measure |
Ranibizumab
n=936 Participants
patients treated with 0.5mg ranibizumab
|
Unilaterally Treted
n=823 Participants
|
Bilaterally Treated
n=113 Participants
|
|---|---|---|---|
|
Mean Number of Injections Per Patient
|
5.97 injections
Standard Deviation 3.62
|
5.35 injections
Standard Deviation 2.88
|
10.55 injections
Standard Deviation 4.98
|
Adverse Events
Ranibizumab 0.5 mg
Serious events: 63 serious events
Other events: 76 other events
Deaths: 9 deaths
Serious adverse events
| Measure |
Ranibizumab 0.5 mg
n=936 participants at risk
Ranibizumab 0.5 mg
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.21%
2/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Blood and lymphatic system disorders
Bone marrow disorder
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Cardiac disorders
Angina pectoris
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Cardiac disorders
Atrial fibrillation
|
0.21%
2/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Cardiac disorders
Atrioventricular block
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Cardiac disorders
Cardiac arrest
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Cardiac disorders
Cardiac failure
|
0.32%
3/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Cardiac disorders
Myocardial infarction
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Cardiac disorders
Myocardial ischaemia
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Endocrine disorders
Goitre
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Eye disorders
Ocular hypertension
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Eye disorders
Retinal haemorrhage
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Eye disorders
Vitreous haemorrhage
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Gastrointestinal disorders
Faecaloma
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Gastrointestinal disorders
Gastritis
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.21%
2/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Gastrointestinal disorders
Large intestine polyp
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Gastrointestinal disorders
Lumbar hernia
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Gastrointestinal disorders
Vomiting
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
General disorders
Asthenia
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
General disorders
General physical health deterioration
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Hepatobiliary disorders
Hepatic lesion
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Infections and infestations
Escherichia sepsis
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Infections and infestations
Herpes zoster
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Infections and infestations
Influenza
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Infections and infestations
Pneumonia
|
0.53%
5/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Infections and infestations
Pyelonephritis
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Infections and infestations
Sepsis
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Infections and infestations
Urinary tract infection
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Injury, poisoning and procedural complications
Fall
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.75%
7/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Injury, poisoning and procedural complications
Pancreatic injury
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.21%
2/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.32%
3/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer recurrent
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Nervous system disorders
Cerebrovascular accident
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Nervous system disorders
Cognitive disorder
|
0.21%
2/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Nervous system disorders
Dizziness
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Nervous system disorders
Myasthenia gravis
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Nervous system disorders
Syncope
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Nervous system disorders
Transient ischaemic attack
|
0.32%
3/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Renal and urinary disorders
Acute kidney injury
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Renal and urinary disorders
Haematuria
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Renal and urinary disorders
Renal cyst
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.21%
2/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.21%
2/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.21%
2/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Surgical and medical procedures
Mastectomy
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Surgical and medical procedures
Transurethral prostatectomy
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Vascular disorders
Peripheral artery stenosis
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Vascular disorders
Peripheral ischaemia
|
0.11%
1/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
Other adverse events
| Measure |
Ranibizumab 0.5 mg
n=936 participants at risk
Ranibizumab 0.5 mg
|
|---|---|
|
Eye disorders
Cataract
|
1.1%
10/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Eye disorders
Conjunctival haemorrhage
|
1.4%
13/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Eye disorders
Neovascular age-related macular degeneration
|
3.6%
34/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
General disorders
Pyrexia
|
1.1%
10/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
|
Infections and infestations
Influenza
|
1.6%
15/936 • Adverse events are reported from time of first treatment until study exit (approximately 12 months)
This reporting group (Safety Population) includes all treated participants (one or both eyes).
|
Additional Information
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