Age-Related Macular Degeneration
Conditions
Keywords
LUV, Lucentis, Visudyne, PDT, AMD, ARMD, Age, Related, Macular, Degeneration
Brief summary
The PDT/Lucentis trial will be a Phase IV comparative trial comparing the use of combination therapy with ITV ranibizumab and verteporfin PDT to ITV ranibizumab alone in patients with exudative AMD.
Detailed description
The PDT/Lucentis trial will be a Phase IV comparative trial comparing the use of combination therapy with ITV ranibizumab and verteporfin PDT to ITV ranibizumab alone in patients with exudative AMD. Patients will be randomized to one of three groups. All patients will receive three consecutive monthly treatments with ITV ranibizumab. Patients randomized to group I will receive only ITV ranibizumab. Patients randomized to group II will also receive one treatment with reduced fluence (20% fluence) verteporfin PDT at day 0. Patients randomized to group III will also receive one treatment with reduced fluence (40% fluence) vPDT. All patients will also be evaluated for possible retreatment with ranibizumab according to established criteria. Thirty patients (ten per group) will be recruited from one U.S. sites in a 6-month period. Randomization will occur at the time of entry into the study. Follow-up will continue until month 12 (from day 0) in all subjects.
Interventions
as needed, one intravitreal injection of 0.50mg ranibizumab
as needed, one intravitreal injection of 0.50mg ranibizumab
Sponsors
Novartis Pharmaceuticals
David M. Brown, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age \> 55 years * Subfoveal neovascular membrane confirmed by fluorescein angiography and or ICG * Visual acuity not better than 20/32 and not worse than 20/320 by ETDRS refraction
Exclusion criteria
* Any previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery) * Intracapsular cataract extraction (posterior capsule needs to be present) * Previous treatment with ranibizumab * Previous treatment with pegaptanib * Previous treatment with ITV triamcinolone * Any previous treatment with photodynamic therapy * Previous history of retinal detachment in study eye * Any previous radiation treatments to head/ neck * Significant cardiovascular disease or cancer that would prevent follow-up visits or completion of the 12 month study * Prior enrollment in any study for AMD in the study eye * Participation in another simultaneous medical investigator or trial * Ocular disorders in the study eye that may confound interpretation of study results, including retinal detachment or macular hole. * Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the study period * Aphakia or absence of the posterior capsule in the study eye * Previous violation of the posterior capsule is also excluded unless it occurred as a result of YAG laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation * History of idiopathic or autoimmune uveitis in either eye * Significant structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s) * Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT * Ocular inflammation (including trace or above) in the study eye * Uncontrolled glaucoma (defined as intraocular pressure ≥30 mm Hg despite treatment with anti- medications) or previous filtration surgery in the study eye * Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye) or current treatment for serious systemic infection * Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia (For patients who have had refractive or cataract surgery in the study eye, pre-operative spherical equivalent refractive error of more than -8 diopters myopia is not allowed) Systemic Conditions * Uncontrolled Blood pressure exceeding diastolic pressure of 100 mm Hg (sitting) during the screening period * Uncontrolled diabetes mellitus * Renal failure requiring dialysis or renal transplant * Premenopausal women not using adequate contraception * Previous participation in other studies of investigational drugs (excluding vitamins and minerals) within 3 months preceding Day 0 * History of other disease, metabolic dysfunction, physical examination finding, or other findings giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications * INR ≥ 3.0 (e.g. due to current treatment with warfarin). The use of aspirin is not an exclusion. Other * History of allergy to fluorescein, not amenable to treatment * History of allergy to shellfish * History of allergy to intravenous iodine * History of allergy to indocyanine green * Inability to obtain fundus photographs or angiograms of sufficient quality to be analyzed and graded by the central reading center * Inability to comply with study or follow up procedures * History of allergy to humanized antibodies or any component of the ranibizumab formulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best-corrected ETDRS Visual Acuity at 6 Months and 12 Months Only Time Points (Gain or Loss of >15 Letters at 12 Months) | 1 Year | Visual Acuity was measured by ETDRS by certified refractionists in certified lanes at 12 months. Visual Acuity was not measured by ETDRS at 6 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Intravitreal Injections With Ranibizumab Needed by Patients at 12 Months | 1 Year | Number of intravitreal injections with ranibizumab needed by patients at 12 months was not determined due to lack of efficacy. |
| OCT 3 Macular Thickness Improvement (Baseline-1month, 2months, 3months, 6months &12 Months) | 1 Year | OCT 3 macular thickness improvement at Baseline-1month, 2months, 3months, 6months &12 months was not determined due to lack of efficacy. |
| Choroidal Perfusion as Assessed by ICG Angiography at 1, 2, 3, 6, and 12 Months | 1 Year | Choroidal perfusion as assessed by ICG angiography at 1, 2, 3, 6, and 12 months was not determined due to lack of efficacy |
| Safety of Combination Therapy With Verteporfin PDT and ITV Ranibizumab | 1 Year | Safety of combination therapy with verteporfin PDT and ITV ranibizumab was not determined due to lack of efficacy. |
Countries
United States
Participant flow
Recruitment details
7 patients, over a 12 month period were followed after receiving treatment of either decreased fluence(2 different fluences) and 0.5mg ranibizumab, as compared to monotherapy of 0.5mg ranibizumab at a single site
Pre-assignment details
patients that were considered to have recalcitrant wet age related macular degeneration were recruited for this trial
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 drug - intravitreal ranibizumab | 2 |
| Arm 2 40% fluence photodynamic therapy - procedure | 3 |
| Arm 3 20% fluence photodynamic therapy - procedure | 2 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Arm 1 | Arm 2 | Arm 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 73 years STANDARD_DEVIATION 3 | 78 years STANDARD_DEVIATION 7 | 67 years STANDARD_DEVIATION 5 | 72 years STANDARD_DEVIATION 5 |
| Region of Enrollment United States | 2 participants | 03 participants | 2 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 2 | 1 / 3 | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 | 1 / 3 | 0 / 2 |
Outcome results
Primary
Best-corrected ETDRS Visual Acuity at 6 Months and 12 Months Only Time Points (Gain or Loss of >15 Letters at 12 Months)
Visual Acuity was measured by ETDRS by certified refractionists in certified lanes at 12 months. Visual Acuity was not measured by ETDRS at 6 months.
Time frame: 1 Year
Population: As per subjects participated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab Only | Best-corrected ETDRS Visual Acuity at 6 Months and 12 Months Only Time Points (Gain or Loss of >15 Letters at 12 Months) | 0 participants |
| 40% Fluence PDT/Ranibizumab | Best-corrected ETDRS Visual Acuity at 6 Months and 12 Months Only Time Points (Gain or Loss of >15 Letters at 12 Months) | 0 participants |
| 20% Fluence PDT/Ranibizumab | Best-corrected ETDRS Visual Acuity at 6 Months and 12 Months Only Time Points (Gain or Loss of >15 Letters at 12 Months) | 0 participants |
Secondary
Choroidal Perfusion as Assessed by ICG Angiography at 1, 2, 3, 6, and 12 Months
Choroidal perfusion as assessed by ICG angiography at 1, 2, 3, 6, and 12 months was not determined due to lack of efficacy
Time frame: 1 Year
Secondary
Number of Intravitreal Injections With Ranibizumab Needed by Patients at 12 Months
Number of intravitreal injections with ranibizumab needed by patients at 12 months was not determined due to lack of efficacy.
Time frame: 1 Year
Population: not determined due to lack of efficacy
Secondary
OCT 3 Macular Thickness Improvement (Baseline-1month, 2months, 3months, 6months &12 Months)
OCT 3 macular thickness improvement at Baseline-1month, 2months, 3months, 6months &12 months was not determined due to lack of efficacy.
Time frame: 1 Year
Secondary
Safety of Combination Therapy With Verteporfin PDT and ITV Ranibizumab
Safety of combination therapy with verteporfin PDT and ITV ranibizumab was not determined due to lack of efficacy.
Time frame: 1 Year