A Study Investigating the Efficacy and Safety of Lampalizumab Intravitreal Injections in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration

Geographic Atrophy Clinical Trial

— CHROMA  

Official title:

A Phase III, Multicenter, Randomized, Double-Masked, Sham-Controlled Study to Assess the Efficacy and Safety of Lampalizumab Administered Intravitreally to Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02247479
• Other study ID #: GX29176
• Secondary ID: 2014-000107-27
• Status: Terminated
• Phase: Phase 3
• Start date: September 18, 2014
• Est. completion date: January 29, 2018

Study information

• Verified date: June 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a Phase III, double-masked, multicenter, randomized, sham injection-controlled study evaluating the efficacy and safety of lampalizumab administered by intravitreal injections in participants with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 906
• Est. completion date: January 29, 2018
• Est. primary completion date: January 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Well demarcated area(s) of Geographic Atrophy (GA) secondary to Age-Related Macular Degeneration (AMD) with no evidence of prior or active choroidal neovascularization (CNV) in both eyes

Exclusion Criteria:

Ocular Exclusion Criteria: Study Eye

• History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD

• Previous laser photocoagulation for CNV, diabetic macular edema, retinal vein occlusion, and proliferative diabetic retinopathy

• Previous intravitreal drug delivery (intravitreal corticosteroid injection, anti-angiogenic drugs, anti-complement agents, or device implantation) Ocular Exclusion Criteria: Both Eyes

• GA in either eye due to causes other than AMD

• Previous treatment with eculizumab, lampalizumab and/or fenretinide

Related Conditions & MeSH terms

• Atrophy
• Geographic Atrophy
• Macular Degeneration

Intervention

Drug:
• Lampalizumab
Participants will receive 10 mg dose of lampalizumab administered intravitreally.

Other:
• Sham
A sham injection is a procedure that mimics an intravitreal injection of lampalizumab.

Locations

Country	Name	City	State
Argentina	Organizacion Medica de Investigacion	Buenos Aires
Argentina	Fundacion Zambrano	Caba
Argentina	Oftar	Mendoza
Argentina	Grupo Laser Vision	Rosario
Argentina	Microcirugía Ocular S.A	Rosario
Australia	Eyeclinic Albury Wodonga	Albury	New South Wales
Australia	Marsden Eye Research Centre	Parramatta	New South Wales
Australia	Save Sight Institute	Sydney	New South Wales
Australia	Sydney West Retina	Westmead	New South Wales
Austria	Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Augenheilkunde	Linz
Belgium	CHU Brugmann (Victor Horta)	Bruxelles
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Sint Rafael	Leuven
Belgium	CHU Sart-Tilman	Liège
Canada	Institut De L'Oeil Des Laurentides	Boisbriand	Quebec
Canada	Calgary Retina Consultants	Calgary	Alberta
Canada	QEII - HSC Department of Ophthalmology	Halifax	Nova Scotia
Canada	University of Ottawa Eye Institute	Ottawa	Ontario
Canada	St. Michael'S Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network Toronto Western Hospital	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
Denmark	Sjællands Universitetshospital, Roskilde; Øjenafdelingen	Roskilde
France	Chi De Creteil; Ophtalmologie	Creteil
France	Centre Odeon; Exploration Ophtalmologique	Paris
France	Centre Ophtalmologique; Imagerie et laser	Paris
France	Ch Pitie Salpetriere; Ophtalmologie	Paris
France	Hopital Lariboisiere; Ophtalmologie	Paris
France	CHU Poitiers - CHR La Miletrie; Ophtalmologie	Poitiers
Germany	Universitäts-Augenklinik Bonn	Bonn
Germany	Universitätsmedizin Göttingen Georg-August-Universität; Klinik für Augenheilkunde	Göttingen
Germany	Medizinische Hochschule Hannover, Klinik für Augenheilkunde	Hannover
Germany	Universitätsklinikum Köln; Augenklinik	Köln
Germany	Universitätskliniikum Schleswig-Holstein, Campus Lübeck, Klinik für Augenheilkunde	Lübeck
Germany	Augenabteilung am St. Franziskus-Hospital	Münster
Germany	Universitätsklinikum Münster; Augenheilkunde	Münster
Hungary	Budapest Retina Associates Kft.	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont; Szemeszeti Klinika	Debrecem
Hungary	Ganglion Medial Center	Pecs
Italy	Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena;U.O.C Oculistica	Milano	Lombardia
Italy	Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia-Presidio Ospedaliero Britannico	Roma	Lazio
Italy	Fondazione Ptv Policlinico Tor Vergata Di Roma;U.O.S.D. Patologie Renitiche	Roma	Lazio
Italy	Azienda Ospedaliero Universitaria Di Sassari;U.O. Oculistica	Sassari	Sardegna
Mexico	Hospital de la Ceguera APEC	Mexico, D.F.
Mexico	Macula Retina Consultores	Mexico, D.F.
Netherlands	Academisch Medisch Centrum Universiteit Amsterdam	Amsterdam
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Radboud University Nijmegen Medical Centre; Ophthalmology	Nijmegen
Peru	Clinica Anglo Americana	Lima
Peru	CLINICA RICARDO PALMA; Oftalmologos Contreras	Lima
Poland	OFTALMIKA Sp. z o.o	Bydgoszcz
Poland	Optimum Profesorskie Centrum Okulistyki	Gdansk
Poland	Gabinet Okulistyczny Prof Edward Wylegala	Katowice
Poland	SP ZOZ Szpital Uniwersytecki w Krakowie Oddzial Kliniczny Okulistyki i Onkologii Okulistycznej	Krakow
Slovakia	Nemocnica sv. Michala, a.s.	Bratislava
Slovakia	Fakultna nemocnica Trencin Ocna klinika	Trencin
Slovakia	Fakultna nemocnica s poliklinikou Zilina; Ocne oddelenie	Zilina
Spain	VISSUM Instituto Oftalmológico de Alicante	Alicante
Spain	Institut de la Macula i la retina	Barcelona
Spain	Instituto Clinico Quirurgico de Oftalmologia - ICQO	Bilbao	Guipuzcoa
Spain	Hospital Universitari de Bellvitge; Servicio de Oftalmologia	Hospitalet De Llobregat	Barcelona
Spain	Hospital General de Catalunya	San Cugat Del Valles	Barcelona
Spain	FISABIO. Fundación Oftalmologica del Mediterraneo	Valencia
Spain	Hospital Universitario Rio Hortega; Servicio de Oftalmologia	Valladolid
Switzerland	Stadtspital Triemli; Augenklinik	Zürich
United Kingdom	Ayr Hospital	AYR
United Kingdom	The Princess Alexandra Eye Pavilion	Edinburgh
United Kingdom	Frimley Park Hospital	Frimley
United Kingdom	Royal Hallamshire Hospita	Sheffield
United States	Retina Consultants of Hawaii	'Aiea	Hawaii
United States	Retina Res Institute of Texas	Abilene	Texas
United States	Texas Retina Associates	Arlington	Texas
United States	Western Carolina Retinal Associate PA	Asheville	North Carolina
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Retina Associates	Austin	Texas
United States	Retina Research Center	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	Retina Assoc of Cleveland Inc	Beachwood	Ohio
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Uni of Alabama At Birmingham Clinical Research Unit	Birmingham	Alabama
United States	Retina Center of New Jersey	Bloomfield	New Jersey
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Tufts Medical Center Research	Boston	Massachusetts
United States	Florida Eye Microsurgical Inst	Boynton Beach	Florida
United States	Northwestern Medical Group/Northwestern University	Chicago	Illinois
United States	Cleveland Clinic Foundation; Cole Eye Institute	Cleveland	Ohio
United States	UT Southwestern MC at Dallas	Dallas	Texas
United States	New Jersey Retina Research Foundation	Edison	New Jersey
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Vitreo-Retinal Associates	Grand Rapids	Michigan
United States	Long Is. Vitreoretinal Consult	Hauppauge	New York
United States	Midwest Eye Institute Northside	Indianapolis	Indiana
United States	The Gavin Herbert Eye Institute - UC, Irvine	Irvine	California
United States	Specialty Eye Institute	Jackson	Michigan
United States	Charleston Neuroscience Inst	Ladson	South Carolina
United States	Retina Consultants of Nevada	Las Vegas	Nevada
United States	Delaware Valley Retina Assoc	Lawrenceville	New Jersey
United States	Lahey Clinic Med Ctr	Lexington	Kentucky
United States	Retina Associates of Kentucky	Lexington	Kentucky
United States	Eye Surgical Associates	Lincoln	Nebraska
United States	Jules Stein Eye Institute/ UCLA	Los Angeles	California
United States	Opthalmic Consultants of LI	Lynbrook	New York
United States	University of Wisconsin	Madison	Wisconsin
United States	Georgia Retina PC	Marietta	Georgia
United States	Valley Retina Institute P.A.	McAllen	Texas
United States	Florida Eye Associates	Melbourne	Florida
United States	Retina Vitreous Consultants	Monroeville	Pennsylvania
United States	West Virginia University Eye Institute	Morgantown	West Virginia
United States	Tennessee Retina PC.	Nashville	Tennessee
United States	Vanderbilt	Nashville	Tennessee
United States	New York Eye & Ear Infirmary	New York	New York
United States	University Retina and Macula Associates, PC	Oak Forest	Illinois
United States	East Bay Retina Consultants	Oakland	California
United States	Retina Consultants of Western New York	Orchard Park	New York
United States	Bascom Palmer Eye Institute	Palm Beach Gardens	Florida
United States	Retina Care Specialists	Palm Beach Gardens	Florida
United States	Southern CA Desert Retina Cons	Palm Desert	California
United States	Retina Specialty Institute	Pensacola	Florida
United States	Retinal Research Institute, LLC	Phoenix	Arizona
United States	Fort Lauderdale Eye Institute	Plantation	Florida
United States	Maine Eye Center	Portland	Maine
United States	Eye Surgeons of Richmond Inc. dba Virginia Eye Institute	Richmond	Virginia
United States	Retina Institute of Virginia	Richmond	Virginia
United States	Assoc Retinal Consultants PC	Royal Oak	Michigan
United States	Retina Vitreous Assoc of FL	Saint Petersburg	Florida
United States	Retina Associates of Utah	Salt Lake City	Utah
United States	UCSF; Ophthalmology	San Francisco	California
United States	W Coast Retina Med Group Inc	San Francisco	California
United States	Orange County Retina Med Group	Santa Ana	California
United States	California Retina Consultants	Santa Barbara	California
United States	Retina Associates	Shawnee Mission	Kansas
United States	Retina Center Northwest	Silverdale	Washington
United States	Retina Consultants of Michigan	Southfield	Michigan
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	Retina Vit Surgeons/Central NY	Syracuse	New York
United States	Southern Vitreoretinal Assoc	Tallahassee	Florida
United States	Retina Associates of Florida, LLC	Tampa	Florida
United States	Retina Specialists	Towson	Maryland
United States	Retina Centers P.C.	Tucson	Arizona
United States	Virginia Retina Center	Warrenton	Virginia
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Associates in Ophthalmology	West Mifflin	Pennsylvania
United States	Strategic Clinical Research Group, LLC	Willow Park	Texas
United States	Wake Forest Baptist Health Eye Centre	Winston-Salem	North Carolina
United States	Vitreo-Retinal Associates, PC	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Hungary,  Italy,  Mexico,  Netherlands,  Peru,  Poland,  Slovakia,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluoresence (FAF) at Week 48	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 GA lesion area (worsening; disease progression).	Baseline, Week 48
Primary	Change From Baseline in GA Area in Complement Factor I (CFI) Positive and Negative Participants at Week 48	For CFI profile, positive or negative biomarker status refers to the presence (carrier) or absence of the risk allele at CFI and at least one risk allele at complement factor H (CFH) or risk locus containing both complement component 2 and complement factor B (C2/CFB).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 GA lesion area (worsening; disease progression).	Baseline, Week 48
Secondary	Change From Baseline in Number of Absolute Scotomatous Points as Assessed by Mesopic Micrometry at Week 48	Scotomatous points were the testing points on microperimetry examination that were centered on the macula and reported a lack of retinal sensitivity within the range tested, a maximum of 68 points were tested within this range. Higher results indicate expansion of absolute scotoma and higher number of abolute scotomatous points. Mesopic microperimetry assessments were performed post-dilation on the study eye only, and the data was forwarded to the central reading center. The data was collected up to Week 48 instead of Week 96, due to early termination of the study. A positive change from baseline indicates an increase in the number of absolute scotomatous points (more lack of retinal sensitivity); disease worsening.	Baseline, Week 48
Secondary	Change From Baseline in Mean Macular Sensitivity as Assessed by Mesopic Microperimetry at Week 48	Mesopic microperimetry was used to assess macular sensitivity and assessments were performed post-dilation on the study eye only, and the data was forwarded to the central reading center. A negative change from baseline indicates a decrease in the mean macular sensitivity; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Baseline, Week 48
Secondary	Change From Baseline in Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at Week 48	BCVA score was based on the number of letters read correctly on the ETDRS visual acuity chart assessed at a starting distance of 4 meters (m). BCVA score testing was performed prior to dilating the eyes. BCVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A negative change from baseline indicates a decrease in the visual acuity; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Baseline, Week 48
Secondary	Percentage of Participants With Less Than 15 Letters Loss From Baseline in BCVA Score at Week 48	Loss of less than 15 letters from baseline was assessed by the ETDRS chart at a starting distance of 4 meters (m). BCVA was measured using an eye chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Week 48
Secondary	Change From Baseline in Low Luminance Visual Acuity (LLVA) as Assessed by ETDRS Chart Under Low Luminance Conditions at Week 48	The LLVA 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. The assessment was performed prior to dilating the eyes. LLVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Baseline, Week 48
Secondary	Percentage of Participants With Less Than 15 Letters Loss From Baseline in LLVA Score at Week 48	Loss of less than 15 letters from baseline was assessed by the ETDRS chart at a starting distance of 4 m. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Week 48
Secondary	Change From Baseline in Binocular Reading Speed as Assessed by Minnesota Low-Vision Reading Test (MNRead) Charts or Radner Reading Charts at Week 48	MNRead acuity cards were continuous-text reading-acuity cards suitable for measuring the reading acuity and reading speed of normal and low-vision participants. The MNRead acuity cards consisted of single, simple sentences with equal numbers of characters. A stopwatch was used to record time to a tenth of a second. Sentences that could not be read or were not attempted due to vision should be recorded as 0 for time and 10 for errors. The Radner Reading Cards were suitable for measuring reading speed, reading visual acuity, and critical print size. The reading test was stopped when the reading time was longer than 20 seconds or when the participant was making severe errors. A negative change from baseline indicates a decrease in the binocular reading speed; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Baseline, Week 48
Secondary	Change From Baseline in Monocular Maximum Reading Speed as Assessed by MNRead Charts or Radner Reading Charts at Week 48	MNRead acuity cards were continuous-text reading-acuity cards suitable for measuring the reading acuity and reading speed of normal and low-vision participants. The MNRead acuity cards consisted of single, simple sentences with equal numbers of characters. A stopwatch was used to record time to a tenth of a second. Sentences that could not be read or were not attempted due to vision should be recorded as 0 for time and 10 for errors. The Radner Reading Cards were suitable for measuring reading speed, reading visual acuity, and critical print size. The reading test was stopped when the reading time was longer than 20 seconds or when the participant was making severe errors. A negative change from baseline indicates a decrease in the monocular reading speed; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Baseline, Week 48
Secondary	Change From Baseline in National Eye Institute Visual Functioning Questionnaire 25-item (NEI VFQ-25) Version Composite Score at Week 48	NEI-VFQ-25 questionnaire included 25 items based on which overall composite VFQ score and 12 subscales were derived: near activities, distance activities, general health,general vision, ocular pain, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision and peripheral vision. Response to each question converted to 0-100 score. Each subscale, total score=average of items contributing to score. For each subscale and total score, score range: 0 to 100, a higher score represents better functioning. A negative change from baseline indicates a decrease in the visual functioning; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Baseline, Week 48
Secondary	Change From Baseline in NEI VFQ-25 Near Activity Subscale Score at Week 48	NEI-VFQ-25 questionnaire included 25 items based on which near activities were measured. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf. Response to each question converted to 0-100 score. Subscale=average of items contributing to score. For this subscale the score range is 0 to 100, a higher score represents better functioning. A negative change from baseline indicates a decrease in the near visual activities; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Baseline, Week 48
Secondary	Change From Baseline in NEI VFQ-25 Distance Activity Subscale Score at Week 48	NEI-VFQ-25 questionnaire included 25 items based on which distance activities were measured. Distance activities are defined as reading street signs or names on stores, and going down stairs, steps, or curbs. Response to each question converted to 0-100 score. Subscale=average of items contributing to score. For this subscale the score range is 0 to 100, a higher score represents better functioning. A negative change from baseline indicates a decrease in the distance visual activities; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Baseline, Week 48
Secondary	Change From Baseline in Mean Functional Reading Independence (FRI) Index at Week 48	The FRI was an interviewer-administered questionnaire with 7 items on functional reading activities most relevant to GA AMD participants. It has one total index score. For each FRI Index reading activity performed in the past 7 days, participants were asked about the extent to which they required vision aids, adjustments in the activity, or help from another participant. Mean FRI Index scores range from 1 to 4, with higher scores indicating greater independence. A negative change from baseline indicates a decrease in the FRI; disease worsening. The data was collected up to Week 48 instead of Week 96, due to early termination of the study.	Baseline, Week 48