Age-related Macular Degeneration, Choroidal Neo-Vascular Age-onset Macular Degeneration
Conditions
Keywords
AMD, macular degeneration, Everolimus, Lucentis, Ranibizumab, Choroidal Neo-Vascular (CNV) age-onset macular degeneration, Age-related Macular Degeneration (AMD)
Brief summary
The study will assess the safety and efficacy of Everolimus (RAD001) alone or in combination with Lucentis in patients with neo-vascular age related macular degeneration (AMD)
Interventions
DRUGEverolimus
5 mg oral tablet
DRUGRanibizumab
0.5 mg administered by intravitreal injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with neovascular Age-Related Macular Degeneration (AMD) * Best corrected visual acuity ( BCVA) of 20/40 or worse in study eye * Patients with predominantly classic, minimally classic, or occult choroidal neovascularization in the macula of one eye (the study eye) who have had an inadequate response to VEGF inhibitors in the study eye. Inadequate response is defined as a gain of less than one line of visual acuity and persistent macular edema (central sub-fiel thickness ≥ 300 μm as measured by Optical Coherence Tomography (OCT) despite a minimum of 3 treatments with Lucentis or Avastin
Exclusion criteria
* Any concurrent ocular condition in the study eye that may result in substantial change in vision during the study * Uncontrolled medical conditions such as cancer, angina, diabetes, viral or fungal infections, impaired lung function, history of stroke * Patients who have macular edema in the study eye that, in the judgment of the investigator, is unlikely to respond to treatment. Examples of features that may guide the investigator's judgment about unresponsiveness are large regions of geographic atrophy, retinal angiomatous proliferation, or large regions of sub-retinal fibrosis. The presence of one of these features excludes a patient only if the investigator judges the study eye to have irreversible macular edema. * active bacterial, fungal or viral infections at the time of enrollment, e.g. hepatitis B or C infection. Patients with risk factors for hepatitis B should be tested for hepatitis B viral load and serological markers at screening (a positive HBV-DNA, HBsAg). Patients with risk factors for hepatitis C should be tested using HCVRNA-PCR at screening. A clinical history of hepatitis B or hepatitis C will exclude the patient from the study. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) | Baseline and 4 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | 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. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Everolimus 5 mg 5 mg orally once daily plus sham ocular injection on Day 1 (Baseline) | 8 |
| Ranibizumab 0.5 mg Ranibizumab intra-vitreal therapy (IVT) 0.5 mg on Day 1 (baseline) | 1 |
| Everolimus and Ranibizumab Everolimus oral 5 mg once daily plus ranibizumab Intra-vitreal therapy (IVT) 0.5 mg on day 1 (baseline) | 7 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Everolimus 5 mg | Ranibizumab 0.5 mg | Everolimus and Ranibizumab | Total |
|---|---|---|---|---|
| Age Continuous | 75.9 years STANDARD_DEVIATION 3.44 | 71.00 years | 78.1 years STANDARD_DEVIATION 14.23 | 76.6 years STANDARD_DEVIATION 9.49 |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 5 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 |
Outcome results
Primary
Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Everolimus 5 mg | 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 |
| Oral Everolimus 5 mg | 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 |
| Oral Everolimus 5 mg | 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 |
| Ranibizumab 0.5 mg | Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) | Week 4 | 308.0 µm | — |
| Ranibizumab 0.5 mg | Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) | Baseline | 306.0 µm | — |
| Ranibizumab 0.5 mg | Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) | Change from Baseline | 2.0 µm | — |
| Everolimus 5 mg and Ranibizumab 0.5 mg | Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) | Baseline | 244.3 µm | Standard Deviation 80.37 |
| Everolimus 5 mg and Ranibizumab 0.5 mg | Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) | Change from Baseline | -41.0 µm | Standard Deviation 56.18 |
| Everolimus 5 mg and Ranibizumab 0.5 mg | Change in Central Retinal Thickness From Baseline to Week 4, as Measured by Optical Coherence Tomography (OCT) | Week 4 | 217.6 µm | Standard Deviation 33.87 |
Secondary
Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus
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.
Time frame: Baseline and week 4
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Everolimus 5 mg | Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | 4 Weeks | 43 Letters | Standard Deviation 17.09 |
| Oral Everolimus 5 mg | Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | Baseline | 46 Letters | Standard Deviation 16.91 |
| Oral Everolimus 5 mg | Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | Change in baseline | -3 Letters | Standard Deviation 7.59 |
| Ranibizumab 0.5 mg | Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | Baseline | 67.0 Letters | — |
| Ranibizumab 0.5 mg | Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | 4 Weeks | 69.0 Letters | — |
| Ranibizumab 0.5 mg | Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | Change in baseline | 2.0 Letters | — |
| Everolimus 5 mg and Ranibizumab 0.5 mg | Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | Baseline | 55.3 Letters | Standard Deviation 10.54 |
| Everolimus 5 mg and Ranibizumab 0.5 mg | Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | Change in baseline | 4.4 Letters | Standard Deviation 5.73 |
| Everolimus 5 mg and Ranibizumab 0.5 mg | Change in Visual Acuity From Baseline to Week 4 in Patients Treated With Everolimus | 4 Weeks | 63.2 Letters | Standard Deviation 12.32 |