Safety and Efficacy of ADVM-022 in Treatment-Experienced Patients With Neovascular Age-related Macular Degeneration [LUNA]

A Multi-Center, Randomized, Double-Masked Phase 2 Study to Assess Safety and Efficacy of ADVM-022 (AAV.7m8-aflibercept) in Anti-VEGF Treatment-Experienced Patients With Neovascular (Wet) Age-related Macular Degeneration (nAMD) [LUNA]

Neovascular or wet age-related macular degeneration (nAMD) is a degenerative ocular disease associated with the infiltration of abnormal blood vessels in the retina from the underlying choroid layer and is a leading cause of blindness in patients over 65 years of age. The abnormal angiogenic process in nAMD is stimulated and modulated by vascular endothelial growth factor (VEGF). Treatment of nAMD requires frequent intravitreal (IVT) injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product being developed for the treatment of nAMD and offers the potential for sustained intraocular expression of aflibercept following a single IVT injection. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with nAMD receiving anti-VEGF therapy in clinical practice.

Study Overview

• Status: Active, not recruiting
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Genetic: ADVM-022; Genetic: ADVM-022

Detailed Description

This Phase 2, multi-center, randomized, double-masked, parallel group study is designed to evaluate the safety, tolerability, and efficacy of a single IVT injection of ADVM-022 at one of two doses (2 × 10^11 vg/eye [2E11] or 6 × 10^10 vg/eye [6E10]) accompanied by one of four prophylactic corticosteroid treatment regimens.

Anti-VEGF treatment-experienced study participants meeting the eligibility criteria that will be randomized between the 2E11 vg/eye and 6E10 vg/eye ADVM-022 doses each with 4 prophylaxis arms for a total of 8 treatment arms, and only one eye per study participant will be selected as the study eye.

Safety, tolerability, and efficacy will be evaluated for a period of approximately 5 years from baseline.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Adam Turpcu, PhD; Phone Number: (650) 649-1012; Email: aturpcu@adverum.com
• Study Contact Backup: Name: Sharri Adams-Edwards; Phone Number: (650) 649-1373; Email: LUNA-Clinops@adverum.com

Study Locations

• France
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44093
      • Adverum Clinical Site 502
  • Rhône
    • Lyon, Rhône, France, 69004
      • Adverum Clinical Site 501
  • Val-de-Marne
    • Créteil, Val-de-Marne, France, 94000
      • Adverum Clinical Site 500
• United Kingdom
  • London, United Kingdom, EC1V 2PD
    • Adverum Clinical Site 600
  • Oxford, United Kingdom, OX3 9DU
    • Adverum Clinical Site 601
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Adverum Clinical Site 178
    • Phoenix, Arizona, United States, 85053
      • Adverum Clinical Site 126
    • Tucson, Arizona, United States, 85704
      • Adverum Clinical Site 159
  • California
    • Beverly Hills, California, United States, 90211
      • Adverum Clinical Site 100
    • Encino, California, United States, 91436
      • Adverum Clinical Site 172
    • Fullerton, California, United States, 92835
      • Adverum Clinical Site 169
    • Pasadena, California, United States, 91105
      • Adverum Clinical Site 170
    • Poway, California, United States, 92064
      • Adverum Clinical Site 174
    • Riverside, California, United States, 92505
      • Adverum Clinical Site 164
    • Sacramento, California, United States, 95817
      • Adverum Clinical Site 166
    • Santa Barbara, California, United States, 93103
      • Adverum Clinical Site 175
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Adverum Clinical Site 116
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Adverum Clinical Site 165
  • Florida
    • Deerfield Beach, Florida, United States, 33064
      • Adverum Clinical Site 124
    • Fort Lauderdale, Florida, United States, 33308
      • Adverum Clinical Site 176
    • Jacksonville, Florida, United States, 32216
      • Adverum Clinical Site 168
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Adverum Clinical Site 149
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Adverum Clinical Site 167
    • Royal Oak, Michigan, United States, 48073
      • Adverum Clinical Site 161
  • Mississippi
    • Southaven, Mississippi, United States, 38671
      • Adverum Clinical Site 163
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Adverum Clinical Site 177
  • Nevada
    • Reno, Nevada, United States, 89502
      • Adverum Clinical Site 119
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08034
      • Adverum Clinical Site 146
    • Teaneck, New Jersey, United States, 07666
      • Adverum Clinical Site 171
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Adverum Clinical Site 122
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Adverum Clinical Site 144
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Adverum Clinical Site 101
  • Texas
    • Abilene, Texas, United States, 79606
      • Adverum Clinical Site 123
    • Austin, Texas, United States, 78705
      • Adverum Clinical Site 154
    • Bellaire, Texas, United States, 77401
      • Adverum Clinical Site 108
    • McAllen, Texas, United States, 78503
      • Adverum Clinical Site 162
    • San Antonio, Texas, United States, 78240
      • Adverum Clinical Site 151
    • The Woodlands, Texas, United States, 77384
      • Adverum Clinical Site 107
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Adverum Clinical Site 152

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female participants, ≥ 50 years of age
• Willing and able to provide written, signed informed consent for this study
• Demonstrated a meaningful response to anti-VEGF therapy
• Participants must be under active anti-VEGF treatment for wet AMD and received a minimum of 2 injections within 4 months prior to screening for the treatment of choroidal neovascularization secondary to nAMD in the study eye
• Vision of the study eye at Baseline: BCVA in the range of 25 - 83 ETDRS letters, inclusive (approximate Snellen equivalent visual acuity range of 20/25 - 20/320)
• Vision of the non-study eye at Baseline: BCVA ≥ 35 ETDRS letters (approximate Snellen equivalent of 20/200 or better)

Exclusion Criteria:

• Any condition that could affect the interpretation of results or render the participant at high risk of treatment complications in the opinion of the Investigator
• Ocular or periocular infection or intraocular inflammation in either eye within 1 month prior to or at the Randomization Visit (Day -7)
• Uncontrolled diabetes or HbA1c ≥ 7.0 %
• History or evidence of significant uncontrolled concomitant disease within 6 months of the Screening visit
• Any history of ongoing bleeding disorders or INR >3.0
• History or evidence of macular or retinal disease other than nAMD
• History or evidence of retinal detachment or retinal pigment epithelium rip/tear
• Uncontrolled ocular hypertension or glaucoma
• Prior treatment with photodynamic therapy or retinal laser for the treatment of nAMD
• Any history of vitrectomy or any other vitreoretinal surgery
• Prior treatment with gene therapy at any time or any non-gene therapy investigational treatment or medical device in the study eye within 3 months of the Screening Visit or 5 half-lives of the investigational medicinal product

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 1; A single intravitreal injection of ADVM-022 2E11 vg/eye	Genetic: ADVM-022; A single IVT injection of 2E11 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens; Genetic: ADVM-022; A single IVT injection of 6E10 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens
Experimental: Dose 2; A single intravitreal injection of ADVM-022 6E10 vg/eye	Genetic: ADVM-022; A single IVT injection of 2E11 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens; Genetic: ADVM-022; A single IVT injection of 6E10 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ocular and non-ocular adverse events	Incidence of ocular and non-ocular adverse events	Up to Week 52
Severity of ocular and non-ocular adverse events	Severity of ocular and non-ocular adverse events	Up to Week 52
Mean change in best corrected visual acuity (BCVA) from Baseline	BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)	Baseline up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants from Baseline who lose/gain at least 5, 10 or 15 letters in BCVA	BCVA measured by ETDRS	Baseline up to 5 years
Mean change in BCVA from Baseline	BCVA measured by ETDRS	Baseline up to 5 years
Percentage of participants who are supplemental aflibercept injection-free	Supplemental anti-VEGF treatments required post therapy	Baseline up to 5 years
Percent reduction in annualized anti-VEGF injections	Supplemental annualized anti-VEGF treatments required post therapy to the year prior	Baseline up to 5 years
Mean change in Central Subfield Thickness (CST) from Baseline	To evaluate the effect of ADVM-022 on CST	Baseline up to 5 years
Percentage of participants without CST fluctuations	To evaluate the effect of ADVM-022 on CST	Baseline up to 5 years
Mean number of CST fluctuations from Baseline	To evaluate the effect of ADVM-022 on CST	Baseline up to 5 years
Percentage of participants without post-prophylactic inflammation	To assess the long-term safety and tolerability of a single IVT injection of ADVM-022	Baseline up to 5 years
Incidence of ocular and non-ocular adverse events	To assess the long-term safety and tolerability of a single IVT injection of ADVM-022	Up to 60 months
Severity of ocular and non-ocular adverse events	To assess the long-term safety and tolerability of a single IVT injection of ADVM-022	Up to 60 months

Collaborators and Investigators

• Sponsor: Adverum Biotechnologies, Inc.
• Collaborators: Parexel
• Investigators: Study Director: Kalliopi Stasi, MD, PhD, Adverum Biotechnologies, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2022
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: September 8, 2022
• First Submitted That Met QC Criteria: September 8, 2022
• First Posted (Actual): September 13, 2022

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Wet AMD; Age-related macular degeneration; Eye diseases; Aflibercept; AAV; Gene therapy; Choroidal neovascularization; CNV; Blindness; ADVM-022; AAV.7m8; Anti-VEGF therapy; Adverum; Eye disease; wAMD; nAMD; AAV vector; Best Corrected Visual Acuity; ADVM; ADVM-022-11; Wet macular degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: ADVM-022-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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