Trial Outcomes & Findings for The Efficacy of Oral Everolimus in Patients With Neovascular Age-related Macular Degeneration (NCT NCT00857259)

Last Updated: 2011-08-19

Results Overview

Central retinal thickness was assessed by Optical coherence tomography (OCT). The primary thickness endpoint was the mean thickness of the foveal field of the macula map produced by the analysis of the sequence of six radial scans. Foveal field thickness was the average thickness of a circular field with a diameter of 1 mm. OCT images were analyzed by a central reading center.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

Baseline and 4 weeks

Results posted on

2011-08-19

Participant Flow

Participant milestones

Participant milestones
Measure	Everolimus 5 mg 5 mg orally once daily plus sham ocular injection on Day 1 (Baseline)	Ranibizumab 0.5 mg Ranibizumab intra-vitreal therapy (IVT) 0.5 mg on Day 1 (baseline)	Everolimus and Ranibizumab Everolimus oral 5 mg once daily plus ranibizumab Intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline)
Overall Study STARTED	8	1	7
Overall Study COMPLETED	7	1	6
Overall Study NOT COMPLETED	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus 5 mg 5 mg orally once daily plus sham ocular injection on Day 1 (Baseline)	Ranibizumab 0.5 mg Ranibizumab intra-vitreal therapy (IVT) 0.5 mg on Day 1 (baseline)	Everolimus and Ranibizumab Everolimus oral 5 mg once daily plus ranibizumab Intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline)
Overall Study Protocol Violation	1	0	1

Baseline Characteristics

The Efficacy of Oral Everolimus in Patients With Neovascular Age-related Macular Degeneration

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus 5 mg n=8 Participants 5 mg orally once daily plus sham ocular injection on Day 1 (Baseline)	Ranibizumab 0.5 mg n=1 Participants Ranibizumab intra-vitreal therapy (IVT) 0.5 mg on Day 1 (baseline)	Everolimus and Ranibizumab n=7 Participants Everolimus oral 5 mg once daily plus ranibizumab Intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline)	Total n=16 Participants Total of all reporting groups
Age Continuous	75.9 years STANDARD_DEVIATION 3.44 • n=5 Participants	71.00 years n=7 Participants	78.1 years STANDARD_DEVIATION 14.23 • n=5 Participants	76.6 years STANDARD_DEVIATION 9.49 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 4 weeks

Population: The Per Protocol Analysis Set (PPAS)consisted of all patients in the Full Analysis Set (FAS)who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and had non-missing central retinal thickness values for the study eye at both baseline and Day 28.

Outcome measures

Outcome measures
Measure	Oral Everolimus 5 mg n=6 Participants 5 mg once daily plus sham ocular injection on Day 1 (Baseline)	Ranibizumab 0.5 mg n=1 Participants Ranibizumab intra-vitreal therapy 0.5 mg on Day 1 (baseline)	Everolimus 5 mg and Ranibizumab 0.5 mg n=6 Participants Everolimus orally 5 mg once daily plus Ranibizumab intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline)
Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) Baseline	454.8 µm Standard Deviation 59.56	306.0 µm	244.3 µm Standard Deviation 80.37
Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) Week 4	492.2 µm Standard Deviation 122.16	308.0 µm	217.6 µm Standard Deviation 33.87
Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) Change from Baseline	37.3 µm Standard Deviation 67.31	2.0 µm	-41.0 µm Standard Deviation 56.18

SECONDARY outcome

Timeframe: Baseline and week 4

Best corrected visual acuity (BCVA) was assessed on both eyes. BCVA measurements were taken in sitting position using Early Treatment Diabetic Retinopathy Study (ETDRs)-like visual acuity testing charts at an initial testing distance specific to test charts. BCVA is measured from the number of letters the patient can read on the eye chart.

Outcome measures

Outcome measures
Measure	Oral Everolimus 5 mg n=6 Participants 5 mg once daily plus sham ocular injection on Day 1 (Baseline)	Ranibizumab 0.5 mg n=1 Participants Ranibizumab intra-vitreal therapy 0.5 mg on Day 1 (baseline)	Everolimus 5 mg and Ranibizumab 0.5 mg n=5 Participants Everolimus orally 5 mg once daily plus Ranibizumab intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline)
Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus 4 Weeks	43 Letters Standard Deviation 17.09	69.0 Letters	63.2 Letters Standard Deviation 12.32
Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus Change in baseline	-3 Letters Standard Deviation 7.59	2.0 Letters	4.4 Letters Standard Deviation 5.73
Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus Baseline	46 Letters Standard Deviation 16.91	67.0 Letters	55.3 Letters Standard Deviation 10.54

Adverse Events

Oral Everolimus 5 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Everolimus 5 mg and Ranibizumab 0.5 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 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 the trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER

Measure	Oral Everolimus 5 mg n=8 participants at risk 5 mg once daily plus sham ocular injection on Day 1 (Baseline)	Everolimus 5 mg and Ranibizumab 0.5 mg n=7 participants at risk Everolimus orally 5 mg once daily plus Ranibizumab intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline)
Eye disorders Lacrimation increased	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Eye disorders Macular degeneration	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Eye disorders Optic disc haemorrhage	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Eye disorders Vitreous floaters	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Gastrointestinal disorders Diarrhoea	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	28.6% 2/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Gastrointestinal disorders Mouth ulceration	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Gastrointestinal disorders Nausea	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	28.6% 2/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Gastrointestinal disorders Tongue ulceration	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
General disorders Oedema peripheral	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Infections and infestations Furuncle	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Infections and infestations Nasopharyngitis	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Infections and infestations Pneumonia	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Injury, poisoning and procedural complications Periorbital haematoma	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Investigations Blood cholesterol increased	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Investigations Blood creatine phosphokinase increased	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Investigations Blood lactate dehydrogenase increased	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Investigations Blood triglycerides increased	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Musculoskeletal and connective tissue disorders Osteopenia	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Nervous system disorders Headache	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Nervous system disorders Migraine	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Psychiatric disorders Insomnia	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Vascular disorders Aortic wall hypertrophy	0.00% 0/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	14.3% 1/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.
Vascular disorders Hypertension	12.5% 1/8 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.	0.00% 0/7 Only two arms are represented in the Serious Adverse Events and Adverse Events \> 5% Tables. The Ranibizumab 0.5 mg IVT arm is omitted because there were no SAEs or AEs reported in that treatment group.