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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04435366




Registration number
NCT04435366
Ethics application status
Date submitted
12/05/2020
Date registered
17/06/2020
Date last updated
12/12/2024

Titles & IDs
Public title
A Phase 3 Safety and Efficacy Study of Intravitreal Administration of Zimura (Complement C5 Inhibitor)
Scientific title
A Phase 3 Multicenter, Randomized, Double Masked, Sham- Controlled Clinical Trial to Assess the Safety and Efficacy of Intravitreal Administration of Zimura (Complement C5 Inhibitor) in Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration
Secondary ID [1] 0 0
ISEE2008
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Geographic Atrophy 0 0
Macular Degeneration 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avacincaptad Pegol
Treatment: Drugs - Sham

Experimental: Avacincaptad Pegol - Participants received avacincaptad pegol (ACP) 2 milligram (mg)/eye via intravitreal (IVT) injections monthly through Month 11 (Year 1). At month 12, participants were re-randomized to receive ACP 2 mg/eye via IVT injections monthly from month12 through month 23 (Year 2).

Sham comparator: Sham - Participants received sham injections; through Month 11 (Year 1). At month 12, participants continued to receive monthly sham administration from month 12 through month 23 (Year 2).

Experimental: Avacincaptad pegol and Sham - Participants who received ACP 2mg monthly through Month 11 (Year 1) were re-randomized at month 12, to receive ACP 2 mg/eye via IVT injections every other month at months 13, 15, 17, 19, 21, and 23 and sham injections at months 12, 14, 16,18, 20, and 22.


Treatment: Drugs: Avacincaptad Pegol
Avacincaptad Pegol Intravitreal Injection

Treatment: Drugs: Sham
Sham Administration (includes placement of the blunt opening of an empty, needleless syringe barrel on the conjunctiva in the inferotemporal quadrant of the eyeball to simulate the pressure of an injection)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Mean Rate of Growth (Slope) Estimated Based on GA Area Measured by Autofluorescence (FAF) at 3 Time Points: Baseline, Month 6, and Month 12
Assessment method [1] 0 0
GA was associated with age-related macular degeneration (AMD) and caused bilateral, progressive, and irreversible loss of retinal tissue (photoreceptors, retinal pigment epithelium, and choriocapillaris) leading to a permanent loss of visual function and blindness. The least squares mean used to determine mean rate of change in GA growth (slope) was measured by FAF. LS mean \& SE were based on square-root transformation.
Timepoint [1] 0 0
Baseline to month 12
Primary outcome [2] 0 0
The Mean Rate of Growth (Slope) Estimated Based on GA Area Measured by FAF at 5 Timepoints: Baseline, Month 6, Month 12, Month 18, and Month 24
Assessment method [2] 0 0
GA was associated with AMD and caused bilateral, progressive, and irreversible loss of retinal tissue (photoreceptors, retinal pigment epithelium, and choriocapillaris) leading to a permanent loss of visual function and blindness. The least square mean rate of GA growth (slope) was measured by FAF. LS mean \& SE were based on untransformed data.
Timepoint [2] 0 0
Baseline to month 24
Secondary outcome [1] 0 0
Change From Baseline in Best Corrected Visual Acuity (BCVA) Using Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at 24 Months
Assessment method [1] 0 0
BCVA was assessed using ETDRS visual acuity testing charts. The ETDRS Visual Acuity Score (VAS) is defined as the number of letters read on the ETDRS chart. Minimum and maximum possible scores are 0-100. A higher score represented better visual functioning. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.
Timepoint [1] 0 0
Baseline and month 24
Secondary outcome [2] 0 0
Change From Baseline in Low Luminance (LL) BCVA Using ETDRS Letters at 24 Months
Assessment method [2] 0 0
BCVA was assessed using ETDRS visual acuity testing charts. The ETDRS VAS is defined as the number of letters read on the ETDRS chart. Minimum and maximum possible scores are 0-100. A higher score represented better visual functioning. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. LL BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart.
Timepoint [2] 0 0
Baseline and month 24
Secondary outcome [3] 0 0
Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Scores at 6, 12 and 18 Months
Assessment method [3] 0 0
The National Eye Institute Visual Function Questionnaire-25 (VFQ-25) measured the influence of visual disability and visual symptoms on general health domains. The VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. A higher score represented better visual functioning. Each item was then converted to a 0 to 100 scale so that the lowest and highest possible scores were set at 0 and 100 points, respectively. Each subscale score had a range of 0 to 100 inclusive and were calculated from the re-scaled raw data. A composite score was derived based on the average of the 11 vision-related subscales.
Timepoint [3] 0 0
Baseline, months 6, 12, and 18
Secondary outcome [4] 0 0
Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Scores at 24 Months
Assessment method [4] 0 0
The National Eye Institute Visual Function Questionnaire-25 (VFQ-25) measured the influence of visual disability and visual symptoms on general health domains. The VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. A higher score represented better visual functioning. Each item was then converted to a 0 to 100 scale so that the lowest and highest possible scores were set at 0 and 100 points, respectively. Each subscale score had a range of 0 to 100 inclusive and were calculated from the re-scaled raw data. A composite score was derived based on the average of the 11 vision-related subscales.
Timepoint [4] 0 0
Baseline and month 24
Secondary outcome [5] 0 0
Number of Participants With Categorical One-level Loss in VFQ-25 Subscale
Assessment method [5] 0 0
The National Eye Institute VFQ-25 measured the influence of visual disability and visual symptoms on general health domains. The VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. A higher score represented better visual functioning. Each item was then converted to a 0 to 100 scale so that the lowest and highest possible scores were set at 0 and 100 points, respectively.Categorical one-level loss in each item was defined as decline of one or more levels at Month 24 on the original scale from Baseline (equivalently 20 points for general vision and 25 points for other vision items in a 0 to 100 scale).
Timepoint [5] 0 0
Baseline up to month 24
Secondary outcome [6] 0 0
Time to Persistent Vision Loss
Assessment method [6] 0 0
Vision loss event was defined as a loss of = 15 letters (equivalent to a loss of 3 lines on the ETDRS chart) in BCVA from Baseline measured at any two or more consecutive visits up to Month 24. These parameters were chosen as a 3-line BCVA loss (equivalent to doubling of visual angle) is widely recognized as a significant deterioration in vision and a minimum of two consecutive visits was representative of persistent disease progression. BCVA was assessed using ETDRS visual acuity testing charts. The ETDRS VAS was defined as the number of letters read on the ETDRS chart. Min and max possible scores are 0-100. A higher score represents better visual functioning. Kaplan-Meier method was used for analysis. Participants with an event were reported and not the median time to event.
Timepoint [6] 0 0
Baseline up to month 24

Eligibility
Key inclusion criteria
* Subjects of either gender aged = 50 years
* Diagnosis of Non-foveal GA secondary to dry AMD
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any prior treatment for AMD (dry or wet) or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins and minerals
* Any intraocular surgery or thermal laser within 3 months of trial entry.
* Any prior thermal laser in the macular region, regardless of indication
* Any ocular or periocular infection (including blepharitis), or ocular surface inflammation in the past 12 weeks.
* Previous therapeutic radiation in the region of the study eye
* Any sign of diabetic retinopathy in either eye

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/08/2023
Sample size
Target
Accrual to date
Final
448
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sydney Eye Hospital - Sydney
Recruitment hospital [2] 0 0
Sydney Retina Clinic and Day Surgery - Sydney
Recruitment hospital [3] 0 0
Royal Victorian Eye & Ear Hospital - East Melbourne
Recruitment postcode(s) [1] 0 0
2000 - Sydney
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
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Hawaii
Country [7] 0 0
United States of America
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Illinois
Country [8] 0 0
United States of America
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Indiana
Country [9] 0 0
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Iowa
Country [10] 0 0
United States of America
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Kansas
Country [11] 0 0
United States of America
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Louisiana
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United States of America
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Maryland
Country [13] 0 0
United States of America
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Massachusetts
Country [14] 0 0
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Michigan
Country [15] 0 0
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Minnesota
Country [16] 0 0
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Missouri
Country [17] 0 0
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Nevada
Country [18] 0 0
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New Jersey
Country [19] 0 0
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New York
Country [20] 0 0
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North Carolina
Country [21] 0 0
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Virginia
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United States of America
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Washington
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Argentina
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Caba
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Argentina
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Santa Fe
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Argentina
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Buenos Aires
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Argentina
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Córdoba
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Argentina
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Mendoza
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Argentina
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Rosario
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Austria
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Graz
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Austria
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Innsbruck
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Austria
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Vienna
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Belgium
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Brussels
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Brazil
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Belo Horizonte
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Brazil
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São Paulo
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Brazil
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Vila Clementino
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Alberta
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British Columbia
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Ontario
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Canada
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Ottawa
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Colombia
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Antioquia
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Colombia
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Bogotá
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Croatia
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Osijek
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Czechia
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Smichov
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Estonia
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Tallin
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Estonia
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Tartu
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Bordeaux
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Créteil
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Dijon
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Lyon
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Nantes
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Paris
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Saint-Cyr-sur-Loire
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France
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Écully
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Germany
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Aachen
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Bonn
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Göttingen
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Hamburg
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Lübeck
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Mainz
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Budapest
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Debrecen
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Nyiregyhaza
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Pécs
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Szeged
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Ashkelon
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Israel
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Be'er Ya'aqov
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Israel
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Haifa
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Israel
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Holon
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Israel
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Jerusalem
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Israel
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Petah tikva
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Israel
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Re?ovot
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Israel
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Tel Aviv
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Italy
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Ancona
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Italy
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Bologna
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Italy
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Chieti
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Italy
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Ferrara
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Italy
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Florence
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Italy
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Milan
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Italy
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Naples
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Italy
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Padova
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Italy
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Pisa
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Italy
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Roma
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Italy
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Udine
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Latvia
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Riga
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Poland
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Bydgoszcz
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Poland
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Tarnowskie Góry
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Poland
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Wroclaw
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Poland
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Lódz
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Spain
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Barcelona
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Spain
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Bilbao
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Spain
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Córdoba
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Spain
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Majadahonda
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Spain
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Pamplona
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Spain
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Santiago De Compostela
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Spain
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Valencia
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Spain
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Valladolid
Country [112] 0 0
Spain
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Zaragoza
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Hull

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
IVERIC bio, Inc.
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04435366