Study to assess safety and efficacy of ADVM-022 in patients having already received anti-VEGF treatment for neovascular (wet) age-related macular degeneration (nAMD) [LUNA]
- Conditions
- eovascular (wet) age-related macular degenerationEye Diseases
- Registration Number
- ISRCTN42621450
- Lead Sponsor
- Adverum Biotechnologies Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 72
Current inclusion criteria as of 27/10/2022:
1. Male or female participants, age = 50 years of age
2. Willing and able to provide written, signed informed consent for this study
3. Demonstrated a meaningful response to anti-VEGF therapy.
4. Current evidence of active primary or recurrent sub-foveal choroidal neovascularization (CNV) assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)e 7
5. Subjects must be under active anti-VEGF treatment for wet AMD and received a minimum of 2 injections within 4 months prior to screening
6. BCVA ETDRS Snellen equivalent between =20/32 and =20/320
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Previous inclusion criteria:
1. Ability and willingness to provide informed consent to participate in the study requirements and visits prior to any study procedure
2. Male or female participants, aged 50 years old and over
3. Have CST of at least 275 µm in the study eye at the Screening Visit (Baseline) as assessed by SD-OCT, confirmed by the CRC, and agreed upon by the Investigator
4. The study eye at the Screening Visit (Baseline) must have current evidence of active primary or recurrent subfoveal CNV or CNV with subfoveal involvement with fluid as assessed by SD-OCT, confirmed by the CRC, and agreed upon by the Investigator
5. Received a minimum of 2 anti-VEGF injections in the 4 months prior to the Screening Visit (Baseline), will have received anti-VEGF injections for no more than 3 calendar years (36 months) prior to the Screening Visit, and no anti-VEGF injection in the 28 days prior to receiving aflibercept at Baseline
6. Vision of the study eye at Baseline: BCVA in the range of 25 – 78 ETDRS letters, inclusive (approximate Snellen equivalent visual acuity range of 20/32 – 20/320)
7. Vision of the non-study eye at Baseline: BCVA = 50 ETDRS letters (approximate Snellen equivalent of 20/100 or better)
8. Demonstrate a meaningful anatomic response 7 to 14 days after IVT aflibercept injection administered at the Screening Visit (Baseline) as confirmed by the CRC and agreed upon by the Investigator and defined as:
8.1. Reduction from the Screening Visit (Baseline) in CST by = 20% as assessed using SD-OCT, or
8.2. Reduction of 30% in thickest paracentral subfield within ETDRS 3 mm grid, or
8.3. No anatomical evidence of SRF or IRF if fluid is present at Baseline by clinical examination or SD-OCT
Current exclusion criteria as of 27/10/2022:
1. 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
2. Ocular or periocular infection or intraocular inflammation in either eye within 1 month prior to or at the Randomization Visit (Day -7)
3. Uncontrolled diabetes or HbA1c = 7.0 %
4. History or evidence of significant uncontrolled concomitant disease within 6 months of the Screening visit
5. History within the 12 months prior to Screening or evidence of renal or hepatic dysfunction at Screening
6. Any history of ongoing bleeding disorders or INR >3.0
7. History or evidence of macular or retinal disease other than nAMD
8. Active or history of retinal detachment or retinal pigment epithelium rip/tear
9. Uncontrolled ocular hypertension or glaucoma
10. Prior treatment with photodynamic therapy or retinal laser for the treatment of nAMD
11. Any history of vitrectomy or any other vitreoretinal surgery within 3 months prior to the Randomization Visit (Day -7)
12. Prior treatment with gene therapy
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Previous exclusion criteria:
1. Serum anti-AAV.7m8 neutralizing antibody titer levels of 1:125 or higher determined from blood drawn during the Screening Period (Day -21 to Day -14)
2. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory findings giving reasonable suspicion of a condition that contraindicates the use of ADVM-022, contraindicates the use of systemic prednisone or prednisolone for 10 weeks, compromises the participant’s ability to comply with the planned study activities, or that might affect the interpretation of the results of the study or render the participant at high risk for treatment complications in the opinion of the Investigator
3. Ocular or periocular infection (e.g., conjunctivitis, chalazion, significant blepharitis) or intraocular inflammation (grade trace or above by standardization of uveitis nomenclature (SUN) criteria) in either eye within 1 month prior to or at the Randomization Visit (Day -7) (mild anticipated post-operative inflammation subsequent to the aflibercept injection administered at the Screening Visit that resolved is acceptable)
4. Received any prior gene therapy at any time or any investigational treatment or medical device within 3 months of the Screening Visit or 5 half-lives of the investigational medicinal product (IMP) (whichever is longer) (observational studies involving over the counter (OTC) vitamins, supplements, or diets are not exclusionary)
5. Evidence of poorly controlled diabetes or HbA1c = 7.0 % within the Screening period
6. History or evidence of significant uncontrolled concomitant disease within 6 months of the Screening Visit such as cardiovascular disease, hypertension (defined as blood pressure systolic over 180 mmHg or diastolic over 100 mmHg), or nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders
7. History of allergy to aflibercept, corticosteroid, or fluorescein dye or sodium fluorescein used in angiography (mild allergy amenable to
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> 1. Incidence and severity of ocular and non-ocular adverse events from baseline through Week 50<br> 2. Mean change in BCVA from the Screening Visit (Baseline) using an ETDRS visual acuity chart at Week 50/ End of Study (EOS)<br>
- Secondary Outcome Measures
Name Time Method <br> 1. Percentage of participants who lose/gain at least 5, 10 or 15 letters in BCVA using an ETDRS visual acuity chart compared with Baseline through Week 50.<br> 2. Mean change in BCVA using an ETDRS visual acuity chart from baseline to Week 26.<br> 3. Percentage of participants who are supplemental aflibercept injection-free through Week 50.<br> 4. Percentage reduction in mean rate of anti-VEGF injections over one year relative to number of anti-VEGF injections received in the year prior to Baseline.<br> 5. Mean change in Central Subfield Thickness (CST) as measured on SD-OCT from Baseline through Week 26 and Week 50.<br> 6. Percentage of participants without CST fluctuations > 50 µm as measured on SD-OCT through Week 50.<br>