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

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

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.

Study Overview

• Status: Completed
• Conditions: Geographic Atrophy
• Intervention / Treatment: Drug: Lampalizumab; Other: Sham

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Barnet Dulaney Perkins Eye Center
    • Tucson, Arizona, United States, 85711
      • University of Arizona; Banner University Medical, Department of Opthalmology
  • Arkansas
    • Springdale, Arkansas, United States, 72764
      • Northwest Arkansas Retina Associates
  • California
    • Campbell, California, United States, 95008
      • Retinal Diagnostic Center
    • Encino, California, United States, 91436
      • The Retina Partners
    • Loma Linda, California, United States, 92354
      • Loma Linda University
    • Oceanside, California, United States, 92056
      • San Diego Retina Associates
    • San Francisco, California, United States, 94109
      • West Coast Retina Medical Group
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
  • Colorado
    • Golden, Colorado, United States, 80401
      • Colorado Retina Associates, PC
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Florida Eye Microsurgical Inst
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Palm Beach Gardens, Florida, United States, 33410
      • Retina Care Specialists
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Elman Retina Group
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • VitreoRetinal Surgery
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • The Retina Institute
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Eye Associates of New Mexico
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associate PA
    • Charlotte, North Carolina, United States, 28210
      • Char Eye Ear &Throat Assoc
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
    • Cleveland, Ohio, United States, 44122
      • Retina Assoc of Cleveland Inc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73099
      • Dean McGee Eye Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Retina Cons of Charleston
    • Columbia, South Carolina, United States, 29223
      • Carolina Retina Center PA
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institution
    • Knoxville, Tennessee, United States, 37923
      • Southeastern Retina Associates
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC.
  • Texas
    • Abilene, Texas, United States, 79606
      • W Texas Retina Consultants PA
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
    • DeSoto, Texas, United States, 75115
      • Retina Specialists
  • Virginia
    • Norfolk, Virginia, United States, 23451
      • Wagner Macula & Retina Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2015
• Primary Completion (Actual): June 2, 2017
• Study Completion (Actual): June 2, 2017

Study Registration Dates

• First Submitted: November 7, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 11, 2014

Study Record Updates

• Last Update Posted (Actual): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 23, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Pathological Conditions, Anatomical; Macular Degeneration; Geographic Atrophy; Atrophy
• Other Study ID Numbers: GX29455

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No