E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063947 |
E.1.2 | Term | Geographic atrophy |
E.1.2 | System Organ Class | 100000004853 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy and safety of 10 mg lampalizumab intravitreal injections of administered every 4 weeks (Q4W) or every 6 weeks (Q6W) in patients compared with sham control assessed by change in the geographic atrophy (GA) area from baseline as measured by fundus autofluorescence (FAF). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of lampalizumab compared with sham control with the use of secondary assessments BCVA, microperimetry, reading charts and patient reported questionnaires. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Willingness to provide signed informed consent; additionally, at U.S. sites, patients must provide Health Insurance Portability and Accountability Act (HIPAA) authorization, and in other countries, as applicable according to national laws
- Participants aged >/= 50 years
Ocular Inclusion Criteria: Study Eye
- Well demarcated area(s) of GA secondary to AMD with no evidence of prior or active choroidal neovascularization (CNV)
- BCVA of 20/100 or better (Snellen equivalent) using ETDRS charts at starting distance of 4 m
If BCVA is superior or equal to 20/25, at least one GA lesion must be within 250 micrometers of the foveal centre.
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E.4 | Principal exclusion criteria |
GA Characteristics Exclusion Criteria
- GA in either eye due to causes other than AMD (monogenetic macular dystrophies [e.g., Stargardt disease, cone rod dystrophy] or toxic maculopathies [e.g., chloroquine/hydroxychloroquine maculopathy])
Ocular Exclusion Criteria: Study Eye
- History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
- Previous laser photocoagulation for CNV, diabetic macular edema, retinal vein occlusion, and proliferative diabetic retinopathy
- Prior treatment with Visudyne®, external-beam radiation therapy, or transpupillary thermotherapy
- History of prophylactic subthreshold laser treatment for AMD
- Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection, anti-angiogenic drugs, anti-complement agents, or device implantation). A single intraoperative administration of a corticosteroid during cataract surgery for cystoid macular edema prophylaxis at least 3 months prior to screening is permitted.
Ocular Exclusion Criteria: Non-study eye
- Non-functioning non-study eye defined as either:
BCVA of hand motion or worse OR no physical presence of non-study eye (i.e., monocular)
Ocular Exclusion Criteria: Both Eyes
- Previous treatment with eculizumab or participation in eculizumab studies
- Previous treatment of either eye with lampalizumab
- Previous treatment with fenretinide or participation in fenretinide studies
Concurrent Systemic Conditions Exclusion Criteria
- Uncontrolled blood pressure (defined as systolic >180 mm Hg and/or diastolic >110 mm Hg while patient is sitting) If a patient’s initial measurement exceeds these values, a second reading may be taken 30 or more minutes later. If the patient’s blood pressure must be controlled by anti hypertensive medication, the patient can become eligible if medication is taken continuously for at least 30 days prior to Day 1.
- History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that gives reasonable suspicion of a disease or condition that contraindicates the use of lampalizumab or that might affect interpretation of the results of the study or that renders the patient at high risk of treatment complications
- Treatment for active systemic infection
- Predisposition or history of increased risk of infection
- Active malignancy
- History of allergy to fluorescein that is not amenable to treatment
- History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lampalizumab injection
- Inability to comply with study or follow-up procedures
- Inability to obtain CFP, FAF, and FA of sufficient quality to be analyzed and graded by the central reading center
- Previous participation in any studies of investigational drugs within 3 months preceding Day 1 (excluding vitamins and minerals) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in GA area, as assessed by fundus autofluorescence (FAF) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change in best corrected visual acuity (BCVA), as assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 m
- Change in BCVA, as assessed by the ETDRS chart (at a starting distance of 4 m) under low luminance conditions
Safety:
- Incidence of adverse events relative to sham
- Proportion of patients with confirmed anti-therapeutic antibodies directed against lampalizumab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 8 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Denmark |
France |
Germany |
Hungary |
Italy |
Mexico |
Netherlands |
Peru |
Poland |
Portugal |
Russian Federation |
Slovakia |
Spain |
Sweden |
Switzerland |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |