A Study of Lampalizumab Intravitreal Injections Administered Every Two Weeks or Every Four Weeks to Participants With Geographic Atrophy

Study Overview
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Brief Summary
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This multicenter, randomized, single-masked, sham injection-controlled study will investigate the exposure-response and safety of lampalizumab administered intravitreally every 2 weeks (Q2W) or every 4 weeks (Q4W) for 24 weeks in participants with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). A safety run-in assessment will be conducted prior to initiating enrollment in the randomized study.

Official Title
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A Phase II, Multicenter, Randomized, Single-Masked, Sham Injection-Controlled Exposure-Response Study of Lampalizumab Intravitreal Injections Administered Every Two Weeks or Every Four Weeks to Patients With Geographic Atrophy

Conditions
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Geographic Atrophy

Intervention / Treatment
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* Other: Sham
* Drug: Lampalizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Complement Factor I (CFI) profile biomarker-positive result Women of child bearing potential and men should remain abstinent or use contraceptive methods Exclusion Criteria: History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in study eye Previous subfoveal focal laser photocoagulation in study eye Laser photocoagulation in the study eye Prior treatment with external-beam radiation therapy or transpupillary thermotherapy in study eye Previous intravitreal drug administration in study eye. A single intraoperative administration of a corticosteroid during cataract surgery at least 3 months prior to screening is permitted Previous cell-based intraocular treatment in study eye Intraocular surgery in study eye Uncontrolled glaucoma and history of glaucoma-filtering surgery in study eye History of corneal transplant in study eye GA in either eye due to causes other than AMD Proliferative diabetic retinopathy in either eye Active or history of neovascular (wet) AMD in either eye History of idiopathic or autoimmune-associated uveitis, ocular or intraocular conditions, and infectious or inflammatory ocular disease Active uveitis and infectious conjunctivitis, keratitis, scleritis or endophthalmitis Previous systemic treatment with complement inhibitor and with inhibitors/modulators of visual cycle Previous expression vector mediated intraocular treatments Uncontrolled blood pressure and atrial fibrillation Medical conditions associated with clinically significant risk for bleeding- Predisposition or history of increased risk for infection Active malignancy within the previous 12 months except for appropriately treated carcinoma in situ of cervix, resolved non-melanoma skin carcinoma, and prostate cancer with a Gleason score of less than or equal to 6, and a stable prostate-specific antigen for greater than or equal to (>/=) 12 months History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of lampalizumab injection Women of child bearing potential must have a negative serum pregnancy test within 28 days prior to initiation of study treatment Previous participation in other studies of investigational drugs

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lampalizumab: Open-label Safety Run-In<br>Participants will receive 10 milligrams (mg) lampalizumab intravitreally Q2W during the safety run-in period. | Drug: Lampalizumab<br>* 10 mg dose of lampalizumab administered intravitreally<br>|
| Experimental: Q2W Lampalizumab: Randomized Treatment<br>Participants will receive 10 mg dose of lampalizumab intravitreally Q2W during the 24-week treatment period. | Drug: Lampalizumab<br>* 10 mg dose of lampalizumab administered intravitreally<br>|
| Experimental: Q4W Lampalizumab: Randomized Treatment<br>Participants will receive 10 mg dose of lampalizumab intravitreally Q4W during the 24-week treatment period. | Drug: Lampalizumab<br>* 10 mg dose of lampalizumab administered intravitreally<br>|
| Sham Comparator: Sham: Randomized Treatment<br>Participants randomized to control arms will receive sham injections, that mimics intravitreal injection of lampalizumab. | Other: Sham<br>* Sham injection will be administered as a matching intravitreal injection of lampalizumab.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluorescence (FAF) at Week 24 | GA or the death of photoreceptors and surrounding cells in the retina, is a common condition in participants with age-related macular degeneration (AMD). The death of these photoreceptors results in lesions that cause vision loss. The change in GA lesion area was measured by FAF and analysis of FAF images was performed by the central reading center. A positive change from baseline indicates an increase in size of geographic atrophy lesion area (worsening; disease progression). BCVA=best corrected visual acuity; ETDRS=Early Treatment Diabetic Retinopathy Scale. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentrations of Lampalizumab (Q2W) | Lower than reportable (LTR) results on pre-dose sample were set to 0, and LTR results on post-dose sample were set to half of lower limit of quantification (LLOQ) (0.5 nanograms per milliliter (ng/mL)). | Baseline (Day 1, predose and postdose), Weeks 2,4,8,16 and 24, early termination, unscheduled predose and postdose | 
| Serum Concentrations of Lampalizumab (Q4W) | LTR results on pre-dose sample were set to 0, and LTR results on post-dose sample were set to half of LLOQ (0.5 ng/mL). | Baseline (Day 1, predose and postdose), Weeks 4,8,16 and 24, early termination | 
| Percentage of Participants With Ocular Adverse Events (AEs) | An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, or any deterioration in a laboratory value or other clinical test. Ocular AEs are the events which are localized in the ocular region. | Baseline up to approximately 30 weeks | 
| Percentage of Participants With Systemic (Non-ocular) Adverse Events | An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, or any deterioration in a laboratory value or other clinical test. Non-ocular AEs were the systemic events. | Baseline up to approximately 30 weeks | 
| Percentage of Participants With Anti-Lampalizumab Antibodies | Having treatment-induced anti-drug antibodies (ADAs) was defined as being ADA-negative at baseline and ADA-positive at any post-baseline timepoint. Having treatment-enhanced ADAs was defined as being ADA-positive at baseline with titer values increased by 0.6 titer units at any post-baseline timepoint. | Baseline up to approximately 30 weeks |