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

Neovascular Age-related Macular Degeneration Clinical Trial

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]

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05536973
• Other study ID #: ADVM-022-11
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 23, 2022
• Est. completion date: November 2028

Study information

• Verified date: May 2023
• Source: Adverum Biotechnologies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 69
• Est. completion date: November 2028
• Est. primary completion date: August 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

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
• ADVM-022
A single IVT injection of 6E10 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens

Locations

Country	Name	City	State
France	Adverum Clinical Site 500	Créteil	Val-de-Marne
France	Adverum Clinical Site 501	Lyon	Rhône
France	Adverum Clinical Site 502	Nantes	Loire-Atlantique
United Kingdom	Adverum Clinical Site 600	London
United Kingdom	Adverum Clinical Site 601	Oxford
United States	Adverum Clinical Site 149	'Aiea	Hawaii
United States	Adverum Clinical Site 123	Abilene	Texas
United States	Adverum Clinical Site 154	Austin	Texas
United States	Adverum Clinical Site 108	Bellaire	Texas
United States	Adverum Clinical Site 100	Beverly Hills	California
United States	Adverum Clinical Site 146	Cherry Hill	New Jersey
United States	Adverum Clinical Site 124	Deerfield Beach	Florida
United States	Adverum Clinical Site 167	Detroit	Michigan
United States	Adverum Clinical Site 172	Encino	California
United States	Adverum Clinical Site 176	Fort Lauderdale	Florida
United States	Adverum Clinical Site 169	Fullerton	California
United States	Adverum Clinical Site 168	Jacksonville	Florida
United States	Adverum Clinical Site 116	Lakewood	Colorado
United States	Adverum Clinical Site 162	McAllen	Texas
United States	Adverum Clinical Site 152	Morgantown	West Virginia
United States	Adverum Clinical Site 101	Nashville	Tennessee
United States	Adverum Clinical Site 177	Omaha	Nebraska
United States	Adverum Clinical Site 170	Pasadena	California
United States	Adverum Clinical Site 126	Phoenix	Arizona
United States	Adverum Clinical Site 178	Phoenix	Arizona
United States	Adverum Clinical Site 174	Poway	California
United States	Adverum Clinical Site 144	Rapid City	South Dakota
United States	Adverum Clinical Site 119	Reno	Nevada
United States	Adverum Clinical Site 164	Riverside	California
United States	Adverum Clinical Site 161	Royal Oak	Michigan
United States	Adverum Clinical Site 166	Sacramento	California
United States	Adverum Clinical Site 151	San Antonio	Texas
United States	Adverum Clinical Site 175	Santa Barbara	California
United States	Adverum Clinical Site 163	Southaven	Mississippi
United States	Adverum Clinical Site 171	Teaneck	New Jersey
United States	Adverum Clinical Site 107	The Woodlands	Texas
United States	Adverum Clinical Site 159	Tucson	Arizona
United States	Adverum Clinical Site 165	Waterford	Connecticut
United States	Adverum Clinical Site 122	West Columbia	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Adverum Biotechnologies, Inc.	Parexel

Countries where clinical trial is conducted

United States,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of ocular and non-ocular adverse events	Incidence of ocular and non-ocular adverse events	Up to Week 52
Primary	Severity of ocular and non-ocular adverse events	Severity of ocular and non-ocular adverse events	Up to Week 52
Primary	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	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
Secondary	Mean change in BCVA from Baseline	BCVA measured by ETDRS	Baseline up to 5 years
Secondary	Percentage of participants who are supplemental aflibercept injection-free	Supplemental anti-VEGF treatments required post therapy	Baseline up to 5 years
Secondary	Percent reduction in annualized anti-VEGF injections	Supplemental annualized anti-VEGF treatments required post therapy to the year prior	Baseline up to 5 years
Secondary	Mean change in Central Subfield Thickness (CST) from Baseline	To evaluate the effect of ADVM-022 on CST	Baseline up to 5 years
Secondary	Percentage of participants without CST fluctuations	To evaluate the effect of ADVM-022 on CST	Baseline up to 5 years
Secondary	Mean number of CST fluctuations from Baseline	To evaluate the effect of ADVM-022 on CST	Baseline up to 5 years
Secondary	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
Secondary	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
Secondary	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