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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03525613
Registration number
NCT03525613
Ethics application status
Date submitted
20/04/2018
Date registered
15/05/2018
Date last updated
6/07/2023
Titles & IDs
Public title
A Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration
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Scientific title
A Phase 3, Multi-Center, Randomized, Double-Masked, Sham-Controlled Study to Compare the Efficacy and Safety of Intravitreal Pegcetacoplan Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)
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Secondary ID [1]
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APL2-304
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Geographic Atrophy
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Condition category
Condition code
Eye
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Diseases / disorders of the eye
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Other
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Research that is not of generic health relevance and not applicable to specific health categories listed above
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - APL-2
Treatment: Drugs - APL-2
Other interventions - Sham Procedure
Other interventions - Sham Procedure
Experimental: APL-2 15mg 0.1 mL Monthly for 24 months - A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every month
Experimental: APL-2 15mg 0.1 mL EOM for 24 months - A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every other month
Experimental: Sham Procedure Monthly for 24 months - Sham Procedure monthly for 24 months
Experimental: Sham Procedure Every Other Month for 24 months - Sham Procedure every other month for 24 months
Treatment: Drugs: APL-2
Complement (C3) Inhibitor
Treatment: Drugs: APL-2
Complement (C3) Inhibitor
Other interventions: Sham Procedure
Subjects will receive a Sham procedure every month
Other interventions: Sham Procedure
Subjects will receive a Sham procedure every other month
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12
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Assessment method [1]
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The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure (MMRM) model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
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Timepoint [1]
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Baseline (screening) and Month 12
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Secondary outcome [1]
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LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24
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Assessment method [1]
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The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
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Timepoint [1]
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Baseline (screening) and Month 24
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Secondary outcome [2]
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Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24
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Assessment method [2]
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The mean change in GA lesion area through Month 24 was measured by assuming a piecewise linear trend in time with knots by FAF images at Months 6, 12, 18, and 24 and was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
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Timepoint [2]
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From Baseline (screening) through Month 24
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Secondary outcome [3]
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LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24
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Assessment method [3]
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Mean threshold sensitivity of all points was determined from the mesopic microperimetry as an assessment of the macular functional response. Microperimetry offers the option to test retinal light sensitivity while directly observing the fundus and allows for monitoring of macular function loss associated with GA progression. The microperimetry reading center overlaid the baseline FAF images with GA lesions traced by the imaging reading center and the corresponding macular integrity assessment microperimetry baseline scanning laser ophthalmoscope image and identified perilesional (within 500 microns outside the atrophy border), paralesional (beyond 500 microns outside the atrophy border), and extralesional (outside the atrophy border) loci on the microperimetry grid to determine the mean threshold sensitivity for these 3 areas. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
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Timepoint [3]
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Baseline (screening) and Month 24
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Secondary outcome [4]
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LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24
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Assessment method [4]
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The maximum reading speed of the study eye was calculated per Minnesota Low-Vision Reading Test (MNREAD) or Radner Reading Charts user manuals, with no adjustment for reading inaccuracy. An additional step to cap resulting reading speed values at a maximum of 300 words per minute (wpm) was implemented. Maximum reading speed was calculated as the mean of the 3 highest non-zero reading speeds (or 2, or 1 value, as available), except when all wpm were calculated as 0 then the maximum reading speed was calculated as 0. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
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Timepoint [4]
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Baseline (screening) and Month 24
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Secondary outcome [5]
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LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24
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Assessment method [5]
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The FRI was an interviewer-administered questionnaire with 7 items on functional reading activities most relevant to GA AMD subjects. It had 1 total index score. For each FRI Index reading activity performed in the past 7 days, subjects were asked about the extent to which they required assistance beyond eyeglasses/contact lenses, including the use of low-vision aids, adjustments in the activity, or help from another subject. Mean FRI Index scores ranged from 1 (unable to do independently) to 4 (totally independent), with higher scores indicating higher functional reading independence. A negative change from baseline indicated a decrease in the FRI; disease worsening. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
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Timepoint [5]
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Baseline (screening) and Month 24
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Secondary outcome [6]
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LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24
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Assessment method [6]
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The NL-BCVA was assessed by early treatment diabetic retinopathy study (ETDRS) chart prior to dilating the eyes at a starting distance of 4 meters and ranged from 0 (least score) to 100 (best score). If the 4-meter score was >19 letters read correctly, the visual acuity score was the sum of total letters correctly read at 4 meters plus the addition of 30. If the 4-meter score was =19 letters read correctly, the visual acuity score was the sum of total letters read correctly at 4 meters and total letters read correctly at the 1-meter distance. If no letters were read correctly at either the 4-meter distance or the 1-meter distance, the visual acuity score was 0. A positive change in the value indicated improvement in visual acuity. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
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Timepoint [6]
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Baseline (screening) and Month 24
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Eligibility
Key inclusion criteria
The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria,
the eye with the worst visual acuity at the screening visit will be designated as the study
eye. If both eyes have the same visual acuity, the right eye will be selected as the study
eye.
Ocular- specific inclusion criteria apply to the study eye only, unless otherwise
specified.
- Age = 60 years.
- Normal Luminance best corrected visual acuity of 24 letters or better using Early
Treatment Diabetic Retinopathy Study (ETDRS) charts (approximately 20/320 Snellen
equivalent).
- Clinical diagnosis of GA of the macula secondary to AMD as determined by the
Investigator and confirmed by the Reading Center.
- The GA lesion must meet the following criteria as determined by the central reading
center's assessment of Fundus Autofluorescence (FAF) imaging at screening:
- Total GA area must be = 2.5 and = 17.5 mm2 (1 and 7 disk areas [DA] respectively)
- If GA is multifocal, at least one focal lesion must be = 1.25 mm2 (0.5 DA), with
the overall aggregate area of GA, as specified above in 4a.
- The entire GA lesion must be completely visualized on the macula centered image
and must be able to be imaged in its entirety and not contiguous with any areas
of peripapillary atrophy.
- Presence of any pattern of hyperautofluorescence in the junctional zone of GA.
Absence of hyperautofluorescence (i.e. pattern = none) is exclusionary.
- Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit
the collection of good quality images as determined by the Investigator.
- Meets the following criteria related to microperimetry:
- Able to detect fixation target.
- Total elapsed time to complete the 10-2 68 point exam is = 30 minutes in
duration.
- Reliability test ratio must be = 20%.
- Subject is willing and able to undertake microperimetry assessment in the opinion
of the investigator.
- Female subjects must be:
- Women of non-child-bearing potential (WONCBP), or
- Women of child-bearing potential (WOCBP) with a negative pregnancy test at
screening and must agree to use protocol defined methods of contraception for the
duration of the study and refrain from breastfeeding for the duration of the
study.
- Males with female partners of child-bearing potential must agree to use protocol
defined methods of contraception and agree to refrain from donating sperm for the
duration of the study.
- Willing and able to give informed consent and to comply with the study procedures and
assessments.
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Minimum age
60
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Ocular specific exclusion criteria apply to the study eye only, unless otherwise specified.
- GA secondary to a condition other than AMD such as Stargardt disease, cone rod
dystrophy or toxic maculopathies like plaquenil maculopathy in either eye.
- Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or
an axial length >26 mm.
- Any history or active choroidal neovascularization (CNV), associated with AMD or any
other cause, including any evidence of retinal pigment epithelium rips or evidence of
neovascularization anywhere based on SD-OCT imaging and/or fluorescein angiography as
assessed by the Reading Center.
- Presence of an active ocular disease that in the opinion of the Investigator
compromises or confounds visual function, including but not limited to, uveitis, other
macular diseases (e.g. clinically significant epiretinal membrane (ERM), full
thickness macular hole or uncontrolled glaucoma/ocular hypertension. Benign conditions
in the opinion of the investigator such as peripheral retina dystrophy are not
exclusionary).
- Intraocular surgery (including lens replacement surgery) within 3 months prior to
randomization.
- History of laser therapy in the macular region.
- Aphakia or absence of the posterior capsule. Note: YAG laser posterior capsulotomy for
posterior capsule opacification done at least 60 days prior to screening is not
exclusionary.
- Any ocular condition other than GA secondary to AMD that may require surgery or
medical intervention during the study period or, in the opinion of the Investigator,
could compromise visual function during the study period.
- Any contraindication to IVT injection including current ocular or periocular
infection.
- History of prior intravitreal injection.
- Unable to perform microperimetry reliably in the opinion of the investigator
- Prior participation in another interventional clinical study for intravitreal
therapies in either eye (including subjects receiving sham).
- Prior participation in another interventional clinical study for geographic atrophy in
either eye including investigational oral medication and placebo.
- Participation in any systemic experimental treatment or any other systemic
investigational new drug within 6 weeks or 5 half-lives of the active ingredient
(whichever is longer) prior to the start of study treatment. Note: clinical trials
solely involving observation, over-the-counter vitamins, supplements, or diets are not
exclusionary.
- Medical or psychiatric conditions that, in the opinion of the investigator, make
consistent follow-up over the 24-month treatment period unlikely, or would make the
subject an unsafe study candidate.
- Any screening laboratory value (hematology, serum chemistry or urinalysis) that in the
opinion of the Investigator is clinically significant and not suitable for study
participation.
- Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to
APL-2 or any of the excipients in APL-2 solution.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
31/08/2018
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
28/06/2022
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Sample size
Target
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Accrual to date
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Final
637
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Recruitment in Australia
Recruitment state(s)
NSW,SA,South BlockWA
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Recruitment hospital [1]
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Marsden Eye Specialist - Parramatta
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Adelaide Eye & Retina Clinic - Adelaide
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Save Sight Institute - Sydney
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Lions Eye Institute - Nedlands
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Strathfield Retina Clinic - Strathfield
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Recruitment hospital [6]
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Sydney West Retina - Westmead
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Recruitment postcode(s) [1]
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2150 - Parramatta
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Recruitment postcode(s) [2]
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5000 - Adelaide
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Recruitment postcode(s) [3]
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2000 - Sydney
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Recruitment postcode(s) [4]
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6009 - Nedlands
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Recruitment postcode(s) [5]
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2135 - Strathfield
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Recruitment postcode(s) [6]
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2145 - Westmead
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Recruitment outside Australia
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Bonn
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York
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Apellis Pharmaceuticals, Inc.
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Ethics approval
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Summary
Brief summary
This is a 24-month, Phase III, multicenter, randomized, double-masked, sham-injection
controlled study to assess the efficacy and safety of multiple IVT injections of APL-2 in
subjects with GA secondary to AMD.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03525613
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03525613
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