Age-Related Macular Degeneration
Conditions
Keywords
Age Related macular Degeneration, Macular Degeneration, Drusen, Geographic atrophy, Eculizumab, Soliris
Brief summary
To evaluate the safety and efficacy of eculizumab for the treatment of dry AMD as evaluated by the change in drusen volume and area of geographic atrophy.
Detailed description
This is a randomized, double-arm, double-masked study designed to evaluate the safety and efficacy of eculizumab for the treatment of patients with dry AMD. There are three stages in the study: the screening period, the treatment period, and the follow-up period.During the screening period patients will be evaluated for eligibility. Eligible patients will receive either eculizumab or placebo for 24 weeks. A total of 60 patients will be enrolled and divided equally between the drusen cohort and the GA cohort. A 2:1 randomization will result in 20 patients in each cohort receiving eculizumab while 10 patients receive placebo. The treatment period will begin two weeks after administration of the meningococcal vaccine. During the treatment period, patients will receive eculizumab or placebo over a period of approximately 26 weeks. Patient will treatment according to the following regimen: Induction Period: patient will receive eculizumab 600 mg or 900 mg via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by 900 mg eculizumab for the fifth dose 7 days later (7 ± 2 days). Maintenance Period: patient will receive eculizumab 900 mg or 1200 mg via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days). After the final scheduled dose of eculizumab or Placebo at week 24, patients will return for follow-up exam 2 weeks, 3 months, and 6 months after the final dose.
Interventions
DRUGEculizumab
Induction Period: patient will receive eculizumab 600 mg or 900 mg via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by 900 mg or 1200 mg eculizumab for the fifth dose 7 days later (7 ± 2 days). Maintenance Period: patient will receive eculizumab 900 mg or 1200 mg via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days) until week 24. Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months.
DRUGSaline
Induction Period: patient will receive saline via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by saline for the fifth dose 7 days later (7 ± 2 days). Maintenance Period: patient will receive saline via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days) until week 24. Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months.
Sponsors
Alexion Pharmaceuticals, Inc.
Philip J. Rosenfeld, MD, PhD
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
* Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age \> 50 years * In the study eye(s), the presence of non-exudative AMD documented by fundus photography, autofluorescence, fluorescein angiography, and spectral domain OCT. * Visual acuity of 20/63 or better (BCVA score of at least 59 letters) as measured on an ETDRS chart. * Able and willing to comply with study procedures.
Exclusion criteria
* Visual acuity worse than 20/63 * Any history of choroidal neovascularization in the study eye * Unresolved meningococcal disease. * Confounding ocular conditions such as amblyopia; aphakia; myopia requiring \>6 diopters of correction; pigment epithelial detachment; uncontrolled glaucoma (intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma medication); steroid-induced ocular hypertension; retinal inflammatory disease; central serous choroidopathy; prior or current retinal detachment; macular edema; cystic lesion (individual cysts or cystoid macular edema); ocular herpes simplex virus; severe non-proliferative or worse diabetic retinopathy; anterior ischemic optic neuropathy; RPE tear involving the macula; pseudovitelliform macular degeneration; vitreo-retinal traction maculopathy; vitreous hemorrhage, history of or current rhegmatogenous retinal detachment or macular hole; uveitis; diffuse choroidal atrophy; optic atrophy (as evidenced by pallor); intraocular inflammation; ocular or periocular infection; moderate or worse dry eye syndrome; clinically significant cataract or opacification of the posterior capsule which, in the Investigator's opinion, would progress during the course of the study and could affect central vision; other ocular conditions that the Investigator believes may be a confounding factor in this study * Refusal to be vaccinated against Neisseria meningitides or an active Neisseria meningitides infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Growth of Geographic Atrophy | 6 months |
| Decrease in Drusen Volume | 6 Months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Acuity for Drusen Group | Baseline/ 6 Months | Visual function was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. Maximum score would be 100 letters read and minimum would be count fingers, hand motion and light perception if there were no letters read on the chart. |
| Change in Visual Acuity for Geographic Atrophy Group | Baseline/ 6 Months | Visual function was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. Maximum score would be 100 letters read and minimum would be count fingers, hand motion and light perception if there were no letters read on the chart. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Saline Randomized patients in the drusen or the GA cohort will receive placebo saline infusions as a comparator
Saline: Induction Period: patient will receive saline via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by saline for the fifth dose 7 days later (7 ± 2 days).
Maintenance Period: patient will receive saline via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days) until week 24.
Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months. | 20 |
| Eculizumab Randomized patients in the drusen or the GA cohort will receive active treatment with eculizumab
Eculizumab: Induction Period: patient will receive eculizumab 600 mg or 900 mg via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by 900 mg or 1200 mg eculizumab for the fifth dose 7 days later (7 ± 2 days).
Maintenance Period: patient will receive eculizumab 900 mg or 1200 mg via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days) until week 24.
Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months. | 40 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period | Physician Decision | 1 | 0 |
| Treatment Period | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Eculizumab | Saline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 34 Participants | 17 Participants | 51 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 3 Participants | 9 Participants |
| Age, Continuous | 75.1 years STANDARD_DEVIATION 8 | 75.7 years STANDARD_DEVIATION 8.64 | 75.3 years STANDARD_DEVIATION 8.2 |
| Region of Enrollment United States | 40 participants | 20 participants | 60 participants |
| Sex: Female, Male Female | 19 Participants | 10 Participants | 29 Participants |
| Sex: Female, Male Male | 21 Participants | 10 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 20 | 0 / 40 |
| serious Total, serious adverse events | 0 / 20 | 0 / 40 |
Outcome results
Primary
Decrease in Drusen Volume
Time frame: 6 Months
Population: Drusen Cohort included 10 eyes randomized to saline and 20 eyes randomized to Eculizumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saline | Decrease in Drusen Volume | 0.12 mm^3 | Standard Deviation 0.08 |
| Eculizumab | Decrease in Drusen Volume | 0.15 mm^3 | Standard Deviation 0.17 |
Primary
Growth of Geographic Atrophy
Time frame: 6 months
Population: Geographic Atrophy Cohort included 10 eyes randomized to saline and 20 eyes randomized to Eculizumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saline | Growth of Geographic Atrophy | 0.18 millimeters | Standard Deviation 0.15 |
| Eculizumab | Growth of Geographic Atrophy | 0.19 millimeters | Standard Deviation 0.12 |
Secondary
Change in Visual Acuity for Drusen Group
Visual function was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. Maximum score would be 100 letters read and minimum would be count fingers, hand motion and light perception if there were no letters read on the chart.
Time frame: Baseline/ 6 Months
Population: Drusen Cohort included 10 eyes randomized to saline and 20 eyes randomized to Eculizumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saline | Change in Visual Acuity for Drusen Group | 4.0 letters | Standard Deviation 7 |
| Eculizumab | Change in Visual Acuity for Drusen Group | 2.4 letters | Standard Deviation 3.9 |
Secondary
Change in Visual Acuity for Geographic Atrophy Group
Visual function was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. Maximum score would be 100 letters read and minimum would be count fingers, hand motion and light perception if there were no letters read on the chart.
Time frame: Baseline/ 6 Months
Population: Geographic Atrophy Cohort included 10 eyes randomized to saline and 20 eyes randomized to Eculizumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saline | Change in Visual Acuity for Geographic Atrophy Group | -2.6 letters | Standard Deviation 7.2 |
| Eculizumab | Change in Visual Acuity for Geographic Atrophy Group | 2.5 letters | Standard Deviation 4.1 |