Clinical trial NCT05536973: Safety and Efficacy of ADVM-022 in Treatment-Experienced Patients With Neovascular Age-related Macular Degeneration [LUNA]
Official title: 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]
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Neovascular Age-related Macular Degeneration
Keywords: Aflibercept
Best Corrected Visual Acuity
Adverum
ADVM
ADVM-022
ADVM-022-11
Age-related macular degeneration
Wet macular degeneration
Wet AMD
Choroidal neovascularization
CNV
AAV.7m8
Anti-VEGF therapy
Gene therapy
Blindness
AAV
AAV vector
nAMD
wAMD
Eye disease
Eye diseases
Lead sponsor: Adverum Biotechnologies, Inc.
Sponsor class: INDUSTRY
First posted: 2022-09-13
Enrollment: 69
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of ocular and non-ocular adverse events
timeFrame: Up to Week 52
measure: Severity of ocular and non-ocular adverse events
timeFrame: Up to Week 52
measure: Mean change in best corrected visual acuity (BCVA) from Baseline
timeFrame: Baseline up to Week 52
Secondary outcomes:
measure: Percentage of participants from Baseline who lose/gain at least 5, 10 or 15 letters in BCVA
timeFrame: Baseline up to 5 years
measure: Mean change in BCVA from Baseline
timeFrame: Baseline up to 5 years
measure: Percentage of participants who are supplemental aflibercept injection-free
timeFrame: Baseline up to 5 years
measure: Percent reduction in annualized anti-VEGF injections
timeFrame: Baseline up to 5 years
measure: Mean change in Central Subfield Thickness (CST) from Baseline
timeFrame: Baseline up to 5 years
measure: Percentage of participants without CST fluctuations
timeFrame: Baseline up to 5 years
measure: Mean number of CST fluctuations from Baseline
timeFrame: Baseline up to 5 years
measure: Percentage of participants without post-prophylactic inflammation
timeFrame: Baseline up to 5 years
measure: Incidence of ocular and non-ocular adverse events
timeFrame: Up to 60 months
measure: Severity of ocular and non-ocular adverse events
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Adverum Clinical Site 178
state: Arizona
city: Phoenix
country: United States
facility: Adverum Clinical Site 126
state: Arizona
city: Tucson
country: United States
facility: Adverum Clinical Site 159
state: Arizona
city: Beverly Hills
country: United States
facility: Adverum Clinical Site 100
state: California
city: Encino
country: United States
facility: Adverum Clinical Site 172
state: California
city: Fullerton
country: United States
facility: Adverum Clinical Site 169
state: California
city: Pasadena
country: United States
facility: Adverum Clinical Site 170
state: California
city: Poway
country: United States
facility: Adverum Clinical Site 174
state: California
city: Riverside
country: United States
facility: Adverum Clinical Site 164
state: California
city: Sacramento
country: United States
facility: Adverum Clinical Site 166
state: California
city: Santa Barbara
country: United States
facility: Adverum Clinical Site 175
state: California
city: Lakewood
country: United States
facility: Adverum Clinical Site 116
state: Colorado
city: Waterford
country: United States
facility: Adverum Clinical Site 165
state: Connecticut
city: Deerfield Beach
country: United States
facility: Adverum Clinical Site 124
state: Florida
city: Fort Lauderdale
country: United States
facility: Adverum Clinical Site 176
state: Florida
city: Jacksonville
country: United States
facility: Adverum Clinical Site 168
state: Florida
city: 'Aiea
country: United States
facility: Adverum Clinical Site 149
state: Hawaii
city: Detroit
country: United States
facility: Adverum Clinical Site 167
state: Michigan
city: Royal Oak
country: United States
facility: Adverum Clinical Site 161
state: Michigan
city: Southaven
country: United States
facility: Adverum Clinical Site 163
state: Mississippi
city: Omaha
country: United States
facility: Adverum Clinical Site 177
state: Nebraska
city: Reno
country: United States
facility: Adverum Clinical Site 119
state: Nevada
city: Cherry Hill
country: United States
facility: Adverum Clinical Site 146
state: New Jersey
city: Teaneck
country: United States
facility: Adverum Clinical Site 171
state: New Jersey
city: West Columbia
country: United States
facility: Adverum Clinical Site 122
state: South Carolina
city: Rapid City
country: United States
facility: Adverum Clinical Site 144
state: South Dakota
city: Nashville
country: United States
facility: Adverum Clinical Site 101
state: Tennessee
city: Abilene
country: United States
facility: Adverum Clinical Site 123
state: Texas
city: Austin
country: United States
facility: Adverum Clinical Site 154
state: Texas
city: Bellaire
country: United States
facility: Adverum Clinical Site 108
state: Texas
city: McAllen
country: United States
facility: Adverum Clinical Site 162
state: Texas
city: San Antonio
country: United States
facility: Adverum Clinical Site 151
state: Texas
city: The Woodlands
country: United States
facility: Adverum Clinical Site 107
state: Texas
city: Morgantown
country: United States
facility: Adverum Clinical Site 152
state: West Virginia
city: Nantes
country: France
facility: Adverum Clinical Site 502
state: Loire-Atlantique
city: Lyon
country: France
facility: Adverum Clinical Site 501
state: Rhône
city: Créteil
country: France
facility: Adverum Clinical Site 500
state: Val-de-Marne
city: London
country: United Kingdom
facility: Adverum Clinical Site 600
city: Oxford
country: United Kingdom
facility: Adverum Clinical Site 601
Study officials:
affiliation: Adverum Biotechnologies, Inc.
name: Adam Turpcu, PhD
role: STUDY_DIRECTOR
References: