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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lampalizumab: Open-label Safety Run-In | Experimental | Participants will receive 10 milligrams (mg) lampalizumab intravitreally Q2W during the safety run-in period. |
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| Q2W Lampalizumab: Randomized Treatment | Experimental | Participants will receive 10 mg dose of lampalizumab intravitreally Q2W during the 24-week treatment period. |
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| Q4W Lampalizumab: Randomized Treatment | Experimental | Participants will receive 10 mg dose of lampalizumab intravitreally Q4W during the 24-week treatment period. |
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| Sham: Randomized Treatment | Sham Comparator | Participants randomized to control arms will receive sham injections, that mimics intravitreal injection of lampalizumab. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sham | Other | Sham injection will be administered as a matching intravitreal injection of lampalizumab. |
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barnet Dulaney Perkins Eye Center | Mesa | Arizona | 85206 | United States | ||
| University of Arizona; Banner University Medical, Department of Opthalmology |
A total of 332 participants were screened and 92 participants were randomized out of which 3 participants from one site were removed from the randomized population due to serious good clinical practice (GCP) noncompliance. Out of 89, 4 participants were excluded from the randomized population as they did not have any post-baseline measurement.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sham Q2W | Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks. |
| FG001 | Sham Q4W | Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 24, 2015 |
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| Lampalizumab | Drug | 10 mg dose of lampalizumab administered intravitreally |
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| 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 |
| Tucson |
| Arizona |
| 85711 |
| United States |
| Northwest Arkansas Retina Associates | Springdale | Arkansas | 72764 | United States |
| Retinal Diagnostic Center | Campbell | California | 95008 | United States |
| The Retina Partners | Encino | California | 91436 | United States |
| Loma Linda University | Loma Linda | California | 92354 | United States |
| San Diego Retina Associates | Oceanside | California | 92056 | United States |
| West Coast Retina Medical Group | San Francisco | California | 94109 | United States |
| California Retina Consultants | Santa Barbara | California | 93103 | United States |
| Colorado Retina Associates, PC | Golden | Colorado | 80401 | United States |
| Florida Eye Microsurgical Inst | Boynton Beach | Florida | 33426 | United States |
| National Ophthalmic Research Institute | Fort Myers | Florida | 33912 | United States |
| Florida Eye Associates | Melbourne | Florida | 32901 | United States |
| Retina Care Specialists | Palm Beach Gardens | Florida | 33410 | United States |
| Retina Specialty Institute | Pensacola | Florida | 32503 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Wolfe Eye Clinic | West Des Moines | Iowa | 50266 | United States |
| Elman Retina Group | Baltimore | Maryland | 21237 | United States |
| Vitreoretinal Surgery | Edina | Minnesota | 55435 | United States |
| The Retina Institute | St Louis | Missouri | 63128 | United States |
| Sierra Eye Associates | Reno | Nevada | 89502 | United States |
| Eye Associates of New Mexico | Albuquerque | New Mexico | 87102 | United States |
| Western Carolina Retinal Associate PA | Asheville | North Carolina | 28803 | United States |
| Char Eye Ear &Throat Assoc | Charlotte | North Carolina | 28210 | United States |
| Cincinnati Eye Institute | Cincinnati | Ohio | 45242 | United States |
| Retina Assoc of Cleveland Inc | Cleveland | Ohio | 44122 | United States |
| Dean McGee Eye Institute | Oklahoma City | Oklahoma | 73099 | United States |
| Retina Cons of Charleston | Charleston | South Carolina | 29414 | United States |
| Carolina Retina Center PA | Columbia | South Carolina | 29223 | United States |
| Charles Retina Institution | Germantown | Tennessee | 38138 | United States |
| Southeastern Retina Associates | Knoxville | Tennessee | 37923 | United States |
| Tennessee Retina PC. | Nashville | Tennessee | 37203 | United States |
| W Texas Retina Consultants PA | Abilene | Texas | 79606 | United States |
| Texas Retina Associates | Dallas | Texas | 75231 | United States |
| Retina Specialists | DeSoto | Texas | 75115 | United States |
| Wagner Macula & Retina Center | Norfolk | Virginia | 23451 | United States |
| FG002 | Lampalizumab Q2W | Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks. |
| FG003 | Lampalizumab Q4W | Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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Modified intent-to-treat (mITT) population included participants who were randomly assigned to study treatment and had at least one post-baseline geographic atrophy (GA) area measurement.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sham Q2W | Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks. |
| BG001 | Sham Q4W | Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks. |
| BG002 | Lampalizumab Q2W | Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks. |
| BG003 | Lampalizumab Q4W | Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Geographic Atrophy Area, as Assessed by Fundus Autofluorescence (FAF) | 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. | Mean | Standard Deviation | millimeter square (mm^2) |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Modified intent-to-treat (mITT) population included participants who were randomly assigned to study treatment and had at least one post-baseline GA area measurement. Number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Mean | Standard Error | mm^2 | Baseline, Week 24 |
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| Secondary | 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)). | Pharmacokinetics (PK) population included participants randomized to lampalizumab treatment who received at least one dose of study drug and provided at least one serum sample for determination of lampalizumab. Number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Baseline (Day 1, predose and postdose), Weeks 2,4,8,16 and 24, early termination, unscheduled predose and postdose |
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| Secondary | 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). | PK population included participants randomized to lampalizumab treatment who received at least one dose of study drug and provided at least one serum sample for determination of lampalizumab. Number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Baseline (Day 1, predose and postdose), Weeks 4,8,16 and 24, early termination |
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| Secondary | 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. | Safety analysis population included all randomized participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Baseline up to approximately 30 weeks |
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| Secondary | 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. | Safety analysis population included all randomized participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Baseline up to approximately 30 weeks |
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| Secondary | 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. | Safety analysis population included all randomized participants who received at least one dose of study drug. Number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Number | percentage of participants | Baseline up to approximately 30 weeks |
|
Baseline up to approximately 30 weeks
Safety analysis population included all randomized participants who received at least one dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lampalizumab Q2W | Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks. | 2 | 46 | 7 | 46 | 21 | 46 |
| EG001 | Lampalizumab Q4W | Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks. | 0 | 22 | 3 | 22 | 13 | 22 |
| EG002 | Sham Q2W | Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks. | 0 | 10 | 0 | 10 | 7 | 10 |
| EG003 | Sham Q4W | Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks. | 0 | 11 | 1 | 11 | 7 | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Scleritis | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Uveitis | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA version 20.0 | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA version 20.0 | Systematic Assessment |
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| Postural orthostatic tachycardia syndrome | Cardiac disorders | MedDRA version 20.0 | Systematic Assessment |
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| Abdominal hernia | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA version 20.0 | Systematic Assessment |
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| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA version 20.0 | Systematic Assessment |
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| Malignant melanoma in situ | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 20.0 | Systematic Assessment |
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| Non-hodgkins lymphoma recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 20.0 | Systematic Assessment |
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| Embolic stroke | Nervous system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA version 20.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA version 20.0 | Systematic Assessment |
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| Deafness unilateral | Ear and labyrinth disorders | MedDRA version 20.0 | Systematic Assessment |
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| Middle ear effusion | Ear and labyrinth disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Conjunctival haemorrhage | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Eye pain | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Vitreous floaters | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Vitreous detachment | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Cataract subcapsular | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Photopsia | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Posterior capsule opacification | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Retinal haemorrhage | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Borderline glaucoma | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Cataract nuclear | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Conjunctival oedema | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Eye pruritus | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Eyelid ptosis | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Neovascular age-related macular degeneration | Eye disorders | MedDRA version 20.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
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| Dental caries | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
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| Seasonal allergy | Immune system disorders | MedDRA version 20.0 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
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| Tooth infection | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA version 20.0 | Systematic Assessment |
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| Tooth fracture | Injury, poisoning and procedural complications | MedDRA version 20.0 | Systematic Assessment |
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| Blood glucose increased | Investigations | MedDRA version 20.0 | Systematic Assessment |
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| Neutrophil count increased | Investigations | MedDRA version 20.0 | Systematic Assessment |
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| Prothrombin time prolonged | Investigations | MedDRA version 20.0 | Systematic Assessment |
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| White blood cell count increased | Investigations | MedDRA version 20.0 | Systematic Assessment |
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| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA version 20.0 | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA version 20.0 | Systematic Assessment |
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| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 20.0 | Systematic Assessment |
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| Device breakage | Product Issues | MedDRA version 20.0 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.0 | Systematic Assessment |
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| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.0 | Systematic Assessment |
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The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | (+41) 616878333 | global.trial_information@roche.com |
| Jan 24, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D057092 | Geographic Atrophy |
| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| C005703 | salicylhydroxamic acid |
| C000603963 | lampalizumab |
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| Male |
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| Not Hispanic or Latino |
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| Asian |
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| White |
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| MMRM |
MMRM analysis variables: treatment group, visit, treatment-by-visit interaction, baseline GA area, and BCVA ETDRS chart Snellen equivalent category. |
| 0.3361 |
| Difference in Adjusted Means |
| -0.210 |
| 2-Sided |
| 80 |
| -0.491 |
| 0.071 |
| Superiority |
|
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Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks. |
|
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Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks. |
|
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Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks. |
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| Title | Measurements |
|---|---|
|