신생혈관 연령관련 황반변성(AQUARIUS) 환자 대상 Ixoberogene Soroparvovec(Ixo-vec)의 효능 및 안전성 연구 (AQUARIUS)
신생혈관성 연령관련 황반변성(AQUARIUS) 환자를 대상으로 Ixoberogene Soroparvovec(Ixo-vec)의 효능과 안전성을 평가하기 위한 다기관, 무작위 배정, 이중눈가림, 능동대조군 대조, 3상 연구
This is a multi-center, randomized, double-masked, active-comparator-controlled, Phase 3 study in a broad participant population (treatment-naïve and treatment-experienced) with neovascular (wet) age-related macular degeneration (nAMD). The study will evaluate a single intravitreal (IVT) injection of Ixo-vec compared to intravitreal aflibercept (active comparator). The primary endpoint of this study is the mean change in best corrected visual acuity (BCVA) of Ixo-vec compared to an active comparator measured as an average at Weeks 52 and 56.
Safety, tolerability, and efficacy will be evaluated throughout the study.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
The primary objective of this study is to evaluate the non-inferiority in efficacy of a single IVT injection of Ixo-vec 6 x 10^10 vector genome (vg)/eye compared to an active comparator. Non-inferiority will be evaluated using a pre-specified margin defined in the protocol.
Neovascular AMD 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 IVT injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. Ixo-vec (also known as ADVM-022 or AAV.7m8-aflibercept) is an adeno-associated virus (AAV)-based gene therapy product being developed for the treatment of nAMD. Ixo-vec 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.
Safety, tolerability, and efficacy will be evaluated throughout this study. The primary endpoint of this study is the mean change in BCVA of Ixo-vec compared to an active comparator measured as an average at Weeks 52 and 56 post-treatment.
Due to the long duration of the Screening period, this study will be considered fully enrolled when randomization has been completed.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 3단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Adverum Study Contact
- 전화번호: 650-656-9323
- 이메일: ADVM02213ClinOp@adverum.com
연구 장소
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Arizona
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Mesa, Arizona, 미국, 85206
- 모병
- Adverum Clinical Site 245
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Phoenix, Arizona, 미국, 85020
- 모병
- Adverum Clinical Site 178
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Phoenix, Arizona, 미국, 85014
- 모병
- Adverum Clinical Site 126
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Phoenix, Arizona, 미국, 85020
- 모병
- Adverum Clinical Site 223
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Scottsdale, Arizona, 미국, 85255
- 모병
- Adverum Clinical Site 229
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Sun City, Arizona, 미국, 85351
- 모병
- Adverum Clinical Site 242
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Arkansas
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Springdale, Arkansas, 미국, 72764
- 모병
- Adverum Clinical Site 198
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California
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Bakersfield, California, 미국, 93309
- 모병
- Adverum Clinical Site 109
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Beverly Hills, California, 미국, 90211
- 모병
- Adverum Clinical Site 100
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Campbell, California, 미국, 95008
- 모병
- Adverum Clinical Site 201
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Encino, California, 미국, 91436
- 모병
- Adverum Clinical Site 172
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Fullerton, California, 미국, 92835
- 모병
- Adverum Clinical Site 169
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Huntington Beach, California, 미국, 92647
- 모병
- Adverum Clinical Site 224
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Poway, California, 미국, 92064
- 모병
- Adverum Clinical Site 130
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Redlands, California, 미국, 92374
- 모병
- Adverum Clinical Site 215
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Sacramento, California, 미국, 95825
- 모병
- Adverum Clinical Site 140
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Sacramento, California, 미국, 95841
- 모병
- Adverum Clinical Site 212
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Santa Barbara, California, 미국, 93103
- 모병
- Adverum Clinical Site 175
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Torrance, California, 미국, 90503
- 모병
- Adverum Clinical Site 202
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Walnut Creek, California, 미국, 94598
- 모병
- Adverum Clinical Site 189
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Colorado
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Denver, Colorado, 미국, 80207
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- Adverum Clinical Site 116
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Denver, Colorado, 미국, 800222
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- Adverum Clinical Site 200
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Connecticut
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Waterford, Connecticut, 미국, 06385
- 모병
- Adverum Clinical Site 165
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Florida
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Deerfield Beach, Florida, 미국, 33064
- 모병
- Adverum Clinical Site 124
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Deerfield Beach, Florida, 미국, 33064
- 모병
- Adverum Clinical Site 184
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Fort Lauderdale, Florida, 미국, 33308
- 모병
- Adverum Clinical Site 176
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Fort Myers, Florida, 미국, 33912
- 모병
- Adverum Clinical Site 221
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Gainesville, Florida, 미국, 32607
- 모병
- Adverum Clinical Site 236
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Lakeland, Florida, 미국, 33805
- 모병
- Adverum Clinical Site 214
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Miami Springs, Florida, 미국, 33166
- 모병
- Adverum Clinical Site 168
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Orlando, Florida, 미국, 32806
- 모병
- Adverum Clinical Site 213
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Plantation, Florida, 미국, 33324
- 모병
- Adverum Clinical Site 206
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South Miami, Florida, 미국, 33143
- 모병
- Adverum Clinical Site 183
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St. Petersburg, Florida, 미국, 33711
- 모병
- Adverum Clinical Site 120
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Tampa, Florida, 미국, 33609
- 모병
- Adverum Clinical Site 148
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Winter Haven, Florida, 미국, 33880
- 모병
- Adverum Clinical Site 238
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Georgia
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Augusta, Georgia, 미국, 30909
- 모병
- Adverum Clinical Site 182
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Illinois
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Chicago, Illinois, 미국, 60616
- 모병
- Adverum Clinical Site 246
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Oak Forest, Illinois, 미국, 60452
- 모병
- Adverum Clinical Site 179
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Oak Park, Illinois, 미국, 60304
- 모병
- Adverum Clinical Site 207
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Indiana
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Carmel, Indiana, 미국, 46032
- 모병
- Adverum Clinical Site 205
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Carmel, Indiana, 미국, 46032
- 모병
- Adverum Clinical Site 195
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Carmel, Indiana, 미국, 46032
- 모병
- Adverum Clinical Site 253
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Maryland
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Hagerstown, Maryland, 미국, 21740
- 모병
- Adverum Clinical Site 204
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Hagerstown, Maryland, 미국, 21740
- 모병
- Adverum Clinical Site 197
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Mississippi
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Jackson, Mississippi, 미국, 39202
- 모병
- Adverum Clinical Site 216
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New Jersey
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Bloomfield, New Jersey, 미국, 07003
- 모병
- Adverum Clinical Site 240
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Teaneck, New Jersey, 미국, 07666
- 모병
- Adverum Clinical Site 171
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New York
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Liverpool, New York, 미국, 13088
- 모병
- Adverum Clinical Site 225
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Rochester, New York, 미국, 14620
- 모병
- Adverum Clinical Site 244
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North Carolina
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Asheville, North Carolina, 미국, 28803
- 모병
- Adverum Clinical Site 196
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Cary, North Carolina, 미국, 27511
- 모병
- Adverum Clinical Site 234
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Greensboro, North Carolina, 미국, 27401
- 모병
- Adverum Clinical Site 211
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Greensboro, North Carolina, 미국, 27401
- 모병
- Adverum Clinical Site 219
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Hickory, North Carolina, 미국, 28602
- 모병
- Adverum Clinical Site 220
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Wake Forest, North Carolina, 미국, 27587
- 모병
- Adverum Clinical Site 209
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Ohio
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Beachwood, Ohio, 미국, 44122-5846
- 모병
- Adverum Clinical Site 248
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Cleveland, Ohio, 미국, 44130
- 모병
- Adverum Clinical Site 247
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Oklahoma
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Edmond, Oklahoma, 미국, 73013
- 모병
- Adverum Clinical Site 254
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Oregon
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Portland, Oregon, 미국, 97225
- 모병
- Adverum Clinical Site 252
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Pennsylvania
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Erie, Pennsylvania, 미국, 16505
- 모병
- Adverum Clinical Site 181
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Philadelphia, Pennsylvania, 미국, 19107
- 모병
- Adverum Clinical Site 110
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Philadelphia, Pennsylvania, 미국, 19102
- 모병
- Adverum Clinical Site 239
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South Carolina
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Bluffton, South Carolina, 미국, 29910
- 모병
- Adverum Clinical Site 241
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Ladson, South Carolina, 미국, 29456
- 모병
- Adverum Clinical Site 222
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Tennessee
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Nashville, Tennessee, 미국, 37203
- 모병
- Adverum Clinical Site 101
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Texas
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Arlington, Texas, 미국, 76012
- 모병
- Adverum Clinical Site 145
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Austin, Texas, 미국, 78705
- 모병
- Adverum Clinical Site 127
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Austin, Texas, 미국, 78750
- 모병
- Adverum Clinical Site 243
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Conroe, Texas, 미국, 77384
- 모병
- Adverum Clinical Site 107
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Dallas, Texas, 미국, 75231
- 모병
- Adverum Clinical Site 194
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McAllen, Texas, 미국, 78503
- 모병
- Adverum Clinical Site 162
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San Antonio, Texas, 미국, 78240
- 모병
- Adverum Clinical Site 185
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San Marcos, Texas, 미국, 78666
- 모병
- Adverum Clinical Site 232
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Schertz, Texas, 미국, 78154
- 모병
- Adverum Clinical Site 228
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The Woodlands, Texas, 미국, 77384
- 모병
- Adverum Clinical Site 231
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Tyler, Texas, 미국, 75703
- 모병
- Adverum Clinical Site 237
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Virginia
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Lynchburg, Virginia, 미국, 24502
- 모병
- Adverum Clinical Site 199
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Washington
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Silverdale, Washington, 미국, 98383
- 모병
- Adverum Clinical Site 249
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Able and willing to provide informed consent (or have a legally authorized representative who is able and willing to provide informed consent) prior to any study assessments and procedures and comply with the study requirements and visits.
- Male or female with a diagnosis of CNV secondary to nAMD in the study eye, with nAMD disease activity at Screening Visit 1.
- At least 50 years old at Screening Visit 1.
- An ETDRS BCVA letter score of 35 - 78 (approximate Snellen equivalent of 20/200 to 20/32) in the study eye at Screening Visit 1.
- Demonstrated a meaningful anatomic response to anti-VEGF therapy during screening.
- Able to reliably use eye drops per protocol.
Exclusion Criteria:
General Exclusion Criteria
-
History of a medical condition giving reasonable suspicion of a condition that contraindicates the use of Ixo-vec, 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. History of severe coronavirus disease (COVID-19) infection may meet this exclusion criterion if, in the opinion of the Investigator, it is likely to lead to any important complications.
-
Received any prior gene therapy.
-
Prior treatment with any non-gene therapy investigational medicinal product (IMP) or medical device in the study eye within 3 months of Screening Visit 1 or 5 half-lives of the IMP prior to dosing with Ixo-vec, whichever is longer.
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Female participants who are pregnant or breastfeeding or who intend to become pregnant or breastfeed in the future.
-
History or evidence of any of the following cardiovascular diseases:
- Myocardial infarction in the 6-month period prior to Week 1.
- Uncontrolled hypertension defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg during screening.
- Stroke in the 6-month period prior to Week 1.
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History of ongoing bleeding disorders. The use of aspirin or other anticoagulants (e.g., Factor Xa inhibitors) is permitted.
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Use of systemic immunosuppressive drugs within 90 days prior to Screening Visit 1. Short courses of oral corticosteroids are permitted, as well as any inhaled, intra-articular, nasal or dermal steroid use.
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Evidence of poorly controlled diabetes or glycated hemoglobin (HbA1c) ≥ 8.0% during screening.
Ocular Exclusion Criteria
-
Any active ocular or periocular infection in the study eye from Screening Visit 1.
-
History or evidence of the following in the study eye:
- Intraocular or refractive surgery within 5 months prior to Week 1.
- Any previous penetrating keratoplasty or vitrectomy.
- Any previous panretinal photocoagulation.
- Any previous submacular surgery, other surgical intervention (including port delivery system) or laser treatment for age-related macular degeneration.
-
Any history or evidence of retinal detachment (with or without repair) or retinal pigment epithelium rip/tear in the study eye, as determined by the Investigator during screening or at Week 1.
-
Uncontrolled ocular hypertension or glaucoma in the study eye from Screening Visit 1 to Week 1 or current use of ≥ 2 intraocular pressure (IOP) lowering medications or normal tension glaucoma/suspect in the study eye or history of any of the following procedures in the study eye prior to Week 1:
- Incisional glaucoma surgery (i.e., glaucoma drainage implant/shunt or trabeculectomy)
- Ocular angle-based surgery (i.e., goniotomy or canaloplasty)
- Minimally Invasive Glaucoma Surgery (MIGS) in the study eye.
- Angle-based glaucoma surgery (e.g., Argon or Selective Laser Trabeculoplasty)
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Any history of IOP elevation related to topical steroid administration in either eye.
-
Any history of uveitis or inflammation (grade trace or above) except mild anticipated post operative inflammation that resolved in either eye.
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Any history of treatment with complement inhibitors for geographic atrophy in the study eye.
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Known history of ocular herpes simplex virus, varicella-zoster virus, or cytomegalovirus, including viral uveitis, retinitis, or keratitis in either eye.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 더블
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
실험적: Ixo-vec
Participants will receive 3 monthly loading doses of aflibercept 2 mg IVT, a single IVT injection of Ixo-vec 6 x 10^10 vg/eye at Week 1, and sham injections every 8 weeks. |
Ixo-vec will be administered intravitreally. Aflibercept will be administered intravitreally. |
|
활성 비교기: Aflibercept
Participants will receive 3 monthly loading doses of aflibercept 2 mg IVT, a sham injection at Week 1, and aflibercept 2 mg IVT every 8 weeks. |
Aflibercept will be administered intravitreally. |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Mean Change from Baseline in BCVA Based on an Average at Weeks 52 and 56
기간: Baseline, Week 52 and Week 56
|
BCVA will be measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. |
Baseline, Week 52 and Week 56
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
평균 Aflibercept 유리체강내 주사 횟수
기간: 4주부터 56주까지
|
4주부터 56주까지
|
|
|
4주차부터 56주차까지 BCVA가 73글자 이상인 참가자의 비율
기간: 4주차부터 56주차까지
|
4주차부터 56주차까지
|
|
|
아플리버셉트 주사제 투여를 중단한 참가자 비율
기간: 4주차부터 56주차까지
|
4주차부터 56주차까지
|
|
|
0회 또는 1회 아플리버셉트 주사를 받은 참가자의 비율
기간: 4주차부터 56주차까지
|
4주차부터 56주차까지
|
|
|
Percentage of Participants with Worsened BCVA
기간: Through Week 56
|
BCVA measured by ETDRS. |
Through Week 56
|
|
Percentage of Participants with Improved BCVA
기간: Through Week 56
|
BCVA measured by ETDRS. |
Through Week 56
|
|
Mean Change from Baseline in BCVA Over Time Based on an Average at Weeks 52 and 56
기간: Baseline Through Week 56
|
BCVA measured by ETDRS. |
Baseline Through Week 56
|
|
Mean Change from Week 1 in BCVA Based on an Average at Weeks 52 and 56
기간: Week 1 through Week 56
|
BCVA measured by ETDRS. |
Week 1 through Week 56
|
|
Mean Change in Central Subfield Thickness (CST) from Baseline Over Time Through Week 56
기간: Baseline Through Week 56
|
CST as measured by spectral domain optical coherence tomography (SD-OCT). |
Baseline Through Week 56
|
|
Percentage of Participants with CST ≤ 300 μm Over Time Through Week 56
기간: Through Week 56
|
CST will be assessed by a central reading center (CRC) using SD-OCT. |
Through Week 56
|
|
Mean Number of CST Fluctuations > 50 μm From Week 1 Over Time Through Week 56
기간: Week 1 through Week 56
|
CST will be assessed by a CRC using SD-OCT images and the mean number of fluctuations with thickness of more than 50 μm will be summarized. |
Week 1 through Week 56
|
|
Percentage of Participants with CST Fluctuations > 50 μm from Week 1 Over Time Through Week 56
기간: Week 1 through Week 56
|
CST will be assessed using SD-OCT. |
Week 1 through Week 56
|
|
Percent Reduction in Mean Rate of Annualized Anti-VEGF Injections
기간: Through Week 56
|
Percent reduction in mean rate of annualized anti-VEGF injections will be assessed relative to the reduction in mean rate of annualized anti-VEGF injections received in the year prior to screening in treatment-experienced participants. |
Through Week 56
|
|
Mean Change in Area of Choroidal Neovascularization (CNV) Lesion from Baseline Over Time Through Week 56
기간: Baseline through Week 56
|
CNV is the infiltration of abnormal blood vessels in the retina from the underlying choroid layer. It will be assessed by a CRC using SD-OCT. |
Baseline through Week 56
|
|
Mean Change in Macular Volume from Baseline Over Time Through Week 56
기간: Baseline through Week 56
|
Macular volume will be measured as part of the full ophthalmic examination. |
Baseline through Week 56
|
|
Percentage of Participants Without Intraretinal Fluid (IRF) Over Time Through Week 56
기간: Through Week 56
|
IRF will be assessed using SD-OCT. |
Through Week 56
|
|
Percentage of Participants Without Subretinal Fluid (SRF) Over Time Through Week 56
기간: Through Week 56
|
SRF will be assessed using SD-OCT. |
Through Week 56
|
|
Percentage of Participants Without IRF and/or SRF Over Time Through Week 56
기간: Through Week 56
|
IRF and SRF will be assessed using SD-OCT. |
Through Week 56
|
|
Time to Dry Retina
기간: Through Week 56
|
Dry retina is defined as no IRF or SRF (i.e., absence of both). IRF and SRF will be assessed using SD-OCT. |
Through Week 56
|
|
Time to Sustained Dry Retina
기간: Through Week 56
|
Sustained dry retina is defined as no IRF or SRF (i.e., absence of both) maintained for 2 consecutive visits. |
Through Week 56
|
|
Number of Participants Who Experienced Ocular Adverse Events
기간: Through Week 56
|
The number of participants who experience an ocular adverse event will be summarized. |
Through Week 56
|
|
Number of Participants Who Experienced Mild, Moderate or Severe Ocular Adverse Events
기간: Through Week 56
|
The number of participants who experience a mild, moderate or severe ocular adverse event will be summarized. |
Through Week 56
|
|
Number of Participants Who Experienced Non-ocular Adverse Events
기간: Through Week 56
|
The number of participants who experience a non-ocular adverse event will be summarized. |
Through Week 56
|
|
Number of Participants Who Experienced Mild, Moderate or Severe Non-ocular Adverse Events
기간: Through Week 56
|
The number of participants who experience a mild, moderate or severe non-ocular adverse event will be summarized. |
Through Week 56
|
|
Mean Change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) Total and Subscale Scores
기간: Day 1 to Week 28 and Week 56
|
The NEI VFQ-25 measures vision-targeted patient-reported outcomes of individuals with chronic eye diseases. It comprises 25 questions. The assessment generates an overall composite score and includes the following subscales: global vision rating, difficulty with near vision activities, difficulty with distance vision activities, limitations in social functioning due to vision, role limitations due to vision, dependency on others due to vision, mental health symptoms due to vision, driving difficulties, limitations with peripheral and color vision, and ocular pain. A decrease in the NEI VFQ-25 score represents an improvement in disease severity. |
Day 1 to Week 28 and Week 56
|
|
Mean Change in the 5-item Health-related Quality of Life Questionnaire (EQ-5D-5L)
기간: Day 1 to Week 28 and Week 56
|
The EQ-5D-5L is a concise, generic self-reported health questionnaire which is weighted to reflect the relevant importance to patients of various different health problems. In retinal disease, the questionnaire is used to assess quality of life in the context of vision loss. It measures five parameters; mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the EQ-5D-5L score represents an improvement in disease severity. |
Day 1 to Week 28 and Week 56
|
공동 작업자 및 조사자
수사관
수사관
- 연구 책임자: Adam Turpcu, PhD, Adverum Biotechnologies, Inc.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- ADVM-022-13
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
Adverum is committed to transparency. Appropriately de-identified participant-level data and supporting documents may be shared under appropriate conditions (e.g. when contractually permitted and when participants provide appropriate consent). Individual patient-level data would only be shared following completion of this study (and any associated studies), completion of applicable regulatory submissions, and in accordance with applicable regulations and laws, as well as criteria established by Adverum, our collaborators and/or industry best practices. Shared datasets and/or documents may be de-identified and/or redacted to protect participant identity and to protect sensitive and confidential information. For inquiries, please contact us at datasharing@adverum.com.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
미국에서 제조되어 미국에서 수출되는 제품
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .