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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Stargardt's Macular Dystrophy
• Intervention / Treatment: Drug: avacincaptad pegol; Drug: Sham

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94010
    • Creteil University Eye Clinic University Paris EST
  • Paris, France, 75012
    • Centre ophtalmologique des Quinzes Vingts
  • Rhone-Alpes
    • Lyon, Rhone-Alpes, France, 69004
      • Hôpital de la Croix-Rousse
• Germany
  • Bonn, Germany, 53127
    • University of Bonn
  • München, Germany, 80336
    • Augenklinik der LMU Munchen
  • Tübingen, Germany, 72076
    • University of Tuebingen
• Hungary
  • Budapest, Hungary, H-1083
    • Semmelweis Egyetem
  • Budapest, Hungary, 1133
    • Budapest Retina Institute
  • Debrecen, Hungary, 4032
    • University of Debrecen DE KK Szemészeti Klinika
  • Pécs, Hungary, 7621
    • Ganglion Medical Center
  • Szeged, Hungary, 6720
    • Szegedi Tudomanyegyetem, Szent-Gyorgyi Albert Klinikai Kozpont, Szemeszeti Klinika
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital
  • Petah tikva, Israel, 4941492
    • Rabin Medical Center, Beilinson Campus
  • Reẖovot, Israel, 7610001
    • Kaplan Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel-Aviv Sourasky Medical Center, Ichilov Hospital
• Italy
  • Bologna, Italy, 40138
    • AOU Policlinico Sant'Orsola Malpighi, U.O. Oftalmologia,
  • Florence, Italy, 50121
    • Azienda Ospedaliera Universitaria Careggi
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Naples, Italy, 80131
    • University of Campania Luigi Vanvitelli Eye Clinic
  • Rome, Italy, 00133
    • Fondazione Policlinico Tor Vergata, UOSD Patologie Retiniche
• Spain
  • Barcelona, Spain, 08022
    • Institut de la Macula
• United Kingdom
  • Edinburgh, United Kingdom, EH3 9HA
    • Princess Alexandra Eye Pavillion
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute
  • California
    • Los Angeles, California, United States, 90095
      • Jules Stein Eye Institute/ David Geffen School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32607
      • VitreoRetinal Associates
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute, Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan/Kellogg Eye Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • The Retina Center
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Retina Center of NJ, LLC.
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute/Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Wills Eye Hospital/Mid Atlantic Retina
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Eye Center
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center
  • Texas
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Dallas, Texas, United States, 75231
      • Retina Foundation of the Southwest
    • Willow Park, Texas, United States, 76087
      • Strategic Clinical Research Group
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah John A. Moran Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: avacincaptad pegol; Participants will receive avacincaptad pegol monthly for up to 17 Months.	Drug: avacincaptad pegol; Intravitreal Injection; Other Names: ARC1905; Zimura; Izervay
Sham Comparator: Sham; Participants will receive a matching sham monthly for up to 17 Months.	Drug: Sham; Intravitreal Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Mean change in photopic sensitivity	Photopic sensitivity will be measured by microperimetry.	Baseline up to 18 Months
Mean change in mesopic macular sensitivity	Mesopic macular sensitivity will be measured by microperimetry.	Baseline up to 18 Months
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
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
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
Emergence of at least one new atrophic lesion (DDAF)	The DDAF will be measured by FAF.	Up to 18 Months
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
Number of participants with vital sign abnormalities and/or AEs	Number of participants with potentially clinically significant vital sign values.	Up to 18 Months
Number of participants with ophthalmic abnormalities and/or AEs	Number of participants with potentially clinically significant ophthalmic variables.	Up to 18 Months
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
Number of participants with laboratory value abnormalities and/or AEs	Number of participants with potentially clinically significant laboratory values.	Up to 18 Months

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Medical Director, Astellas Pharma Global Development, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2018
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: December 1, 2017
• First Submitted That Met QC Criteria: December 1, 2017
• First Posted (Actual): December 6, 2017

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 19, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Stargardt's Macular Dystrophy; Zimura; ARC1905; avacincaptad pegol; complement factor C5 inhibitor; STGD1; Izervay; Stargardt Disease 1
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Macular Degeneration; Stargardt Disease
• Other Study ID Numbers: OPH2005; 2017-004783-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No