Zimura Compared to Sham in Patients With Autosomal Recessive Stargardt Disease (STGD1)

Stargardt's Macular Dystrophy Clinical Trial

Official title:

A Phase 2b Randomized, Double-masked, Controlled Trial to Establish the Safety and Efficacy of Zimura™ (Complement C5 Inhibitor) Compared to Sham in Subjects With Autosomal Recessive Stargardt Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03364153
• Other study ID #: OPH2005
• Secondary ID: 2017-004783-35
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 12, 2018
• Est. completion date: April 30, 2025

Study information

• Verified date: June 2024
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of avacincaptad pegol intravitreal injection compared to Sham in participants with autosomal recessive Stargardt disease 1 (STGD1).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 121
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• At least two pathogenic mutations of ATP-Binding Cassette (ABC)A4 gene confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory

• Best corrected visual acuity in the study eye between 20/20 - 20/200 Snellen equivalent, inclusive

Exclusion Criteria:

• Macular atrophy secondary to any condition other than STGD1 in either eye

• Any prior treatment for STGD1 including gene therapy, stem cell therapy or any prior intravitreal treatment for any indication in either eye

• Participation in an interventional study of a vitamin A derivative </= 3 months prior to screening

• Presence of intraocular inflammation, macular hole, pathologic myopia, epiretinal membrane, evidence of significant vitreo-macular traction, vitreous hemorrhage or aphakia

• Any intraocular surgery or thermal laser within 3 months of trial entry. Any prior thermal laser in the macular region

• Diabetes mellitus

• Hemoglobin A1c (HbA1c) value of >/=6.5%

• Stroke within 12 months of trial entry

• Any major surgical procedure within one month of trial entry or anticipated during the trial

• Any treatment with an investigational agent in the past 60 days for any condition

• Women who are pregnant or nursing

• Known serious allergies to the fluorescein dye used in angiography, povidone iodine, or to the components of the avacincaptad pegol formulation

Related Conditions & MeSH terms

• Macular Degeneration
• Stargardt Disease
• Stargardt's Macular Dystrophy

Intervention

Drug:
• avacincaptad pegol
Intravitreal Injection
• Sham
Intravitreal Injection

Locations

Country	Name	City	State
France	Creteil University Eye Clinic University Paris EST	Créteil
France	Hopital de la Croix-Rousse	Lyon	Rhone-Alpes
France	Centre ophtalmologique des Quinzes Vingts	Paris
Germany	University of Bonn	Bonn
Germany	Augenklinik der LMU München	München
Germany	University of Tuebingen	Tübingen
Hungary	Budapest Retina Institute	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	University of Debrecen DE KK Szemészeti Klinika	Debrecen
Hungary	Ganglion Medical Center	Pécs
Hungary	Szegedi Tudomanyegyetem, Szent-Gyorgyi Albert Klinikai Kozpont, Szemeszeti Klinika	Szeged
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah University Hospital	Jerusalem
Israel	Rabin Medical Center, Beilinson campus	Petah tikva
Israel	Kaplan Medical Center	Re?ovot
Israel	Tel-Aviv Sourasky Medical Center, Ichilov Hospital	Tel Aviv
Italy	AOU Policlinico Sant'Orsola Malpighi, U.O. Oftalmologia,	Bologna
Italy	Azienda Ospedaliera Universitaria Careggi	Florence
Italy	Ospedale San Raffaele	Milano
Italy	University of Campania Luigi Vanvitelli Eye Clinic	Naples
Italy	Fondazione Policlinico Tor Vergata, UOSD Patologie Retiniche	Rome
Spain	Institut de la Macula	Barcelona
United Kingdom	Princess Alexandra Eye Pavillion	Edinburgh
United Kingdom	Moorfields Eye Hospital	London
United States	University of Michigan/Kellogg Eye Center	Ann Arbor	Michigan
United States	Austin Retina Associates	Austin	Texas
United States	Wilmer Eye Institute, Johns Hopkins	Baltimore	Maryland
United States	Retina Center of NJ, LLC.	Bloomfield	New Jersey
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	VitreoRetinal Associates	Gainesville	Florida
United States	Jules Stein Eye Institute/ David Geffen School of Medicine	Los Angeles	California
United States	The Retina Center	Minneapolis	Minnesota
United States	Retina Specialty Institute	Pensacola	Florida
United States	Wills Eye Hospital/Mid Atlantic Retina	Philadelphia	Pennsylvania
United States	Retinal Research Institute	Phoenix	Arizona
United States	UPMC Eye Center	Pittsburgh	Pennsylvania
United States	Casey Eye Institute/Oregon Health & Science University	Portland	Oregon
United States	University of Utah John A. Moran Eye Center	Salt Lake City	Utah
United States	Palmetto Retina Center	West Columbia	South Carolina
United States	Strategic Clinical Research Group	Willow Park	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Hungary,  Israel,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean rate of change in the area of ellipsoid zone defect	The ellipsoid zone will be measured through the foveal center with an en face Spectral Domain-Optical Coherence Tomography (SD-OCT).	up to 18 Months
Secondary	Mean rate of change in the horizontal width of undetectable ellipsoid zone	The ellipsoid zone will be measured by a horizontal scan through the foveal center with SD-OCT.	Baseline up to 18 Months
Secondary	Mean rate of change in the area of atrophic lesion (definite decrease in autofluorescence)	The definite decrease in autofluorescence (DDAF) will be measured by fundus autofluorescence (FAF).	Baseline up to 18 Months
Secondary	Mean change in photopic sensitivity	Photopic sensitivity will be measured by microperimetry.	Baseline up to 18 Months
Secondary	Mean change in mesopic macular sensitivity	Mesopic macular sensitivity will be measured by microperimetry.	Baseline up to 18 Months
Secondary	Mean rate of change in the thickness of the outer nuclear layer	The outer nuclear layer will be measured by a horizontal scan through the foveal center at the position of maximum width of ellipsoid zone loss measured by SD-OCT.	Baseline up to 18 Months
Secondary	Mean change in best corrected visual acuity	Best corrected visual acuity (BCVA) will be measured by Early Treatment Diabetic Retinopathy Study [ETDRS] letters chart.	Baseline up to 18 Months
Secondary	Time to persistent vision loss	Vision loss is defined as BCVA loss >/= 10, 15 or 20 letters from Baseline at two or more consecutive visits through Month 18.	Baseline up to 18 Months
Secondary	Emergence of at least one new atrophic lesion (DDAF)	The DDAF will be measured by FAF.	Up to 18 Months
Secondary	Number of participants with Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a participant including unfavorable and unintended signs, symptoms or disease temporally associated with the use of a medicinal product and which does not necessarily have to have a causal relationship to this treatment.; AEs include illnesses with onset during the trial, or exacerbations of pre-existing illnesses. Exacerbation of pre-existing illness is defined as a significant increase in the severity of the illness as compared to the start of the trial and should be considered when a patient requires new or additional treatment for that illness.	Up to 18 Months
Secondary	Number of participants with vital sign abnormalities and/or AEs	Number of participants with potentially clinically significant vital sign values.	Up to 18 Months
Secondary	Number of participants with ophthalmic abnormalities and/or AEs	Number of participants with potentially clinically significant ophthalmic variables.	Up to 18 Months
Secondary	Number of participants with 12-Lead electrocardiogram (ECG) abnormalities and/or AEs	Number of participants with potentially clinically significant 12-Lead ECG values.	Up to 18 Months
Secondary	Number of participants with laboratory value abnormalities and/or AEs	Number of participants with potentially clinically significant laboratory values.	Up to 18 Months