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

• ClinicalTrials.gov Identifier: NCT05536973
• Recruitment Status: Active, not recruiting
• First Posted: September 13, 2022
• Last Update Posted: January 8, 2024
• Sponsor: Adverum Biotechnologies, Inc.
• Collaborator: Parexel
• Information provided by (Responsible Party): Adverum Biotechnologies, Inc.

Tracking Information

• First Submitted Date: September 8, 2022
• First Posted Date: September 13, 2022
• Last Update Posted Date: January 8, 2024
• Actual Study Start Date: August 23, 2022
• Estimated Primary Completion Date: August 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 5, 2024)

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

Original Primary Outcome Measures (submitted: September 8, 2022)

• Severity of ocular and non-ocular adverse events [ Time Frame: From Baseline to Week 50 ]
  Incidence of ocular and non-ocular adverse events
• Incidence of ocular and non-ocular adverse events [ Time Frame: From Baseline to Week 50 ]
  Incidence of ocular and non-ocular adverse events
• Mean change in best corrected visual acuity (BCVA) from Baseline [ Time Frame: Week 50 ]
  BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)

Current Secondary Outcome Measures (submitted: January 5, 2024)

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

Original Secondary Outcome Measures (submitted: September 8, 2022)

• Percentage of participants from Baseline who lose/gain at least 5, 10 or 15 letters in Best Corrected Visual Acuity (BCVA) [ Time Frame: Week 50 ]
  BCVA measured by ETDRS
• Mean change in BCVA from Baseline [ Time Frame: Week 26 ]
  BCVA measured by ETDRS
• Percentage of participants who are supplemental aflibercept injection-free [ Time Frame: Week 50 ]
  Supplemental anti-VEGF treatments required post therapy
• Percentage reduction in anti-VEGF injections [ Time Frame: Week 50 ]
  Supplemental anti-VEGF treatments required post therapy to the year prior
• Mean change in Central Subfield Thickness (CST) from Baseline [ Time Frame: Week 26 and Week 50 ]
  To evaluate the effect of ADVM-022 on CST
• Percentage of participants without CST fluctuations > 50 μm [ Time Frame: Week 50 ]
  To evaluate the effect of ADVM-022 on CST

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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]
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Neovascular Age-related 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
• 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

Study Arms

• Experimental: Dose 1
  A single intravitreal injection of ADVM-022 2E11 vg/eye
  Intervention: Genetic: ADVM-022
• Experimental: Dose 2
  A single intravitreal injection of ADVM-022 6E10 vg/eye
  Intervention: Genetic: ADVM-022

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 5, 2024): 69
• Original Estimated Enrollment (submitted: September 8, 2022): 72
• Estimated Study Completion Date: November 2028
• Estimated Primary Completion Date: August 2028 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, United Kingdom, United States

Administrative Information

• NCT Number: NCT05536973
• Other Study ID Numbers: ADVM-022-11
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Adverum Biotechnologies, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Adverum Biotechnologies, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Parexel

Investigators

• Study Director: Kalliopi Stasi, MD, PhD; Adverum Biotechnologies, Inc.

• PRS Account: Adverum Biotechnologies, Inc.
• Verification Date: May 2023