A Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Intravitreal Injections of RO7303359 in Participants With Geographic Atrophy Secondary to Age-related Macular Degeneration

A Phase 1a, Multicenter, Open-label, Single-dose, Dose-escalation Study of the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Intravitreal Injections of RO7303359 in Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration

This multicenter study will investigate the safety, tolerability, pharmacokinetics, and immunogenicity of RO7303359 following single intravitreal (ITV) injection in participants with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Participants will receive an ITV injection of RO7303359 in the single ascending dose stage and the maximum tolerated dose (MTD) or maximum tested dose (MTeD) of RO7303359 in the expansion stage.

Study Overview

• Status: Completed
• Conditions: Geographic Atrophy
• Intervention / Treatment: Drug: RO7303359

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Sacramento, California, United States, 95825
      • Retinal Consultants Med Group
    • Santa Maria, California, United States, 93454
      • California Retina Consultants - Santa Maria
  • Colorado
    • Denver, Colorado, United States, 80230
      • Colorado Retina Associates, PC
  • Florida
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
  • Illinois
    • Oak Forest, Illinois, United States, 60452
      • University Retina and Macula Associates, PC
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Associated Retinal Consultants PC
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associate PA
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC.
  • Texas
    • Austin, Texas, United States, 78750
      • Austin Clinical Research LLC
    • Dallas, Texas, United States, 75231
      • Retina Foundation of the Southwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Ocular Inclusion Criteria Study Eye:

• Visual acuity: BCVA letter score of 19-48 ETDRS letters (Snellen equivalent of 20/125-20/400) using ETDRS charts at a starting distance of 4 meters
• Well-demarcated area of GA secondary to AMD in the absence of choroidal neovascularization (CNV)
• GA area must be >/= 0.5 disc area (1.25 mm^2)

Ocular Exclusion Criteria, Study Eye:

• GA in the study eye due to causes other than AMD
• History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
• Previous laser photocoagulation for CNV, diabetic macular edema, retinal vein occlusion, or proliferative diabetic retinopathy
• Prior treatment with photodynamic therapy, external beam radiation therapy (for intraocular conditions), or transpupillary thermotherapy

Ocular Exclusion Criteria, Both eyes:

• Evidence of prior or active CNV
• Previous participation in interventional clinical trials for GA or dry AMD, except for vitamins and minerals, irrespective of the route of administration (i.e. ocular or systemic) within the last 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose Stage; Participants will receive a single dose of RO7303359, in multiple escalating cohorts (A-D).	Drug: RO7303359; RO730359 will be administered as a single intravitreal injection.
Experimental: Expansion Cohort Stage; Participants will receive the maximum tolerated dose (MTD) or the maximum tested dose (MTeD) as determined in the single ascending dose stage.	Drug: RO7303359; RO730359 will be administered as a single intravitreal injection.
Experimental: Optional Cohort E; An optional additional cohort may be added with the dose not exceed the MTD or MTeD.	Drug: RO7303359; RO730359 will be administered as a single intravitreal injection.
Experimental: Optional cohort F; An optional additional cohort may be added with the dose not exceed the MTD or MTeD.	Drug: RO7303359; RO730359 will be administered as a single intravitreal injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Ocular Adverse Events	Up to 12 weeks
Percentage of Participants With Systemic Adverse Events	Up to 12 weeks
Percentage of Participants With Dose-limiting Adverse Events (DLAEs),	Up to 12 weeks
Percentage of Participants With Serious Adverse Events (SAEs)	Up to 12 weeks
Percentage of Participants With Adverse Events Leading to Study Discontinuation	Up to 12 weeks
Percentage of Participants With Adverse Events of Special Interest (AESIs)	Up to 12 weeks
Change from Baseline in Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum concentration of RO7303359	Up to 12 Weeks
Aqueous humor concentration of RO7303359	Up to 12 Weeks
Concentration of serum anti drug antibodies (ADAs) at baseline and incidence of serum ADAs	Up to 12 Weeks
Proportion of participants with anti-drug-antibodies (ADA) to RO7303359	Up to 12 Weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Actual): January 4, 2023
• Study Completion (Actual): January 4, 2023

Study Registration Dates

• First Submitted: October 29, 2020
• First Submitted That Met QC Criteria: October 29, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Pathological Conditions, Anatomical; Macular Degeneration; Geographic Atrophy; Atrophy
• Other Study ID Numbers: GR42163

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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