공개 : Angelman 증후군에서 ION582의 3 단계 연구
3 단계 Angelman 증후군이있는 어린이 및 성인의 ION582의 효능 및 안전성에 대한 연구
The purpose of this study is to evaluate the efficacy and safety of obudanersen in children and adults with Angelman syndrome caused by a deletion or mutation of the UBE3A gene.
연구 개요
상세 설명
This is a Phase 3, randomized, double-blind, placebo-controlled study in people with Angelman syndrome. The study will consist of 4 periods: a screening period of up to 28 days, an approximate 60-week double blind, placebo-controlled treatment period, followed by an approximate 25-month Long-Term Extension (LTE) treatment period, and an approximate 8-month Post-LTE follow-up period. The study will be comprised of 2 cohorts. Cohort 1 will include pediatric participants, aged 2 to less than (<)18 years old and serve as the population for evaluation of primary and secondary outcome measures; Cohort 2 will include adult participants, aged 18 to ≤50 years old. Participants will be randomized 1:1 to 80 mg obudanersen or placebo during the double-blind placebo-controlled treatment period. Participants from both cohorts completing the placebo-controlled treatment period will be eligible to transition into the LTE Treatment Period wherein all trial participants will receive obudanersen. Participant, Caregiver, Investigator and Sponsor will remain blinded to the obudanersen dose administered to participants during the LTE.
The study initiated in 2024 with three dosing groups (40 mg obudanersen, 80 mg obudanersen, and placebo). Following additional review of data from the ongoing Phase 1/2 trial of obudanersen (HALOS), REVEAL was amended in December 2025 to its current form as a two-arm study: 80 mg obudanersen and placebo. Following the amendment, participants who were randomized to receive 40 mg obudanersen will be transitioned to receive 80 mg obudanersen.
연구 유형
등록 (실제)
단계
- 3단계
연락처 및 위치
연구 장소
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Seoul, 대한민국, 03080
- Seoul National University Hospital
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Seoul, 대한민국, 06351
- Samsung Medical Center
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München, 독일, 81377
- Klinikum der Ludwig-Maximilians-Universitaet Muenchen
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California
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Los Angeles, California, 미국, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, 미국, 90095
- UCLA Clinical & Translational Research Center (CTRC)
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San Diego, California, 미국, 92123
- Rady Children's Hospital
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Colorado
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Aurora, Colorado, 미국, 80045
- Colorado Children's Hospital Research Institute
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District of Columbia
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Washington D.C., District of Columbia, 미국, 20011
- Children's National Hospital
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Florida
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Miami, Florida, 미국, 33155
- Nicklaus Children's Hospital
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Georgia
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Atlanta, Georgia, 미국, 30329
- Children's Healthcare of Atlanta
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Illinois
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Chicago, Illinois, 미국, 60612
- Rush University Medical Center
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Massachusetts
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Boston, Massachusetts, 미국, 02115
- Boston Children's Hospital
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Missouri
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Kansas City, Missouri, 미국, 64108
- Children's Mercy
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New York
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New York, New York, 미국, 10032
- Columbia University Irving Medical Center
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New York, New York, 미국, 10029
- Ichan School of Medicine at Mount Sinai
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North Carolina
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Carrboro, North Carolina, 미국, 27510
- University of North Carolina at Chapel Hill School of Medicine
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Ohio
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Cincinnati, Ohio, 미국, 45229
- Cincinnati Children's Hospital
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Columbus, Ohio, 미국, 43205
- Nationwide Children's Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19104
- Children's Hospital of Philadelphia
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Tennessee
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Nashville, Tennessee, 미국, 37232
- Vanderbilt Clinical Research Center
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Texas
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Houston, Texas, 미국, 77030
- Texas Children's Hospital
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Barcelona, 스페인, 08950
- Hospital Sant Joan de Deu
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Sabadell, 스페인, 08208
- Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
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Singapore, 싱가포르, 229899
- KK Women's and Children's Hospital
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London, 영국, WC1N 3JH
- Great Ormond Street Hospital for Children - NHS Foundation Trust
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Oxford, 영국, OX3 9DU
- John Radcliffe Hospital
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Ramat Gan, 이스라엘, 5265601
- Sheba Medical Center
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Milan, 이탈리아, 20133
- Fondazione IRCCS Istituto Neurologico Carlo Besta
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Pisa, 이탈리아, 56126
- Azienda Ospedaliero Universitaria Pisana
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Roma, 이탈리아, 00165
- Ospedale Pediatrico Bambino Gesù
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Osaka
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Izumi, Osaka, 일본, 594-1101
- Osaka Women's and Children's Hospital
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Tokyo
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Kodaira, Tokyo, 일본, 187-8551
- National Center of Neurology and Psychiatry
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Edmonton, 캐나다, T6G 2B7
- University of Alberta Hospital
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Vancouver, 캐나다, V6H 3V4
- British Columbia Children's Hospital
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Ontario
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London, Ontario, 캐나다, N6A 5W9
- London Health Science Centre - Children's Hospital
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Quebec
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Montreal, Quebec, 캐나다, H4A 3J1
- McGill University Health Centre
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Gdansk, 폴란드, 80-952
- Uniwersyteckie Centrum Kliniczne
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Heidelberg, 호주, 3084
- Austin Hospital
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Nedlands, 호주, 6009
- Perth Children's Hospital
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Randwick, 호주, 2031
- Sydney Children's Hospital
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Queensland
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South Brisbane, Queensland, 호주, 4101
- Queensland Children's Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Key Inclusion Criteria:
- The participants caregiver(s)/ legally authorized representative must have given written informed consent and any authorizations required by local law and be able to comply with all study requirements.
- Medically stable and can undergo sedation and/or general anesthesia without intubation.
- Male or female between 2 and lesser than or equal to (≤)50 years of age, depending on specific cohort, at the time of the in-clinic Screening visit.
- Participant has a clinical diagnosis of Angelman syndrome (AS) with molecular confirmation of either Ubiquitin-protein ligase E3A (UBE3A) deletion or UBE3A mutation.
- Currently receiving stable doses of concomitant medications typically prescribed for AS, such as anti-epileptic medication, behavioral management medications, sleep medications, gabapentin, cannabidiol, and special diets, supplements, or nutritional support for at least 8 weeks prior to the Baseline visit.
- Legally authorized representative/caregiver(s) agree(s) not to post any of the participant's personal medical data or information related to the study on any website or social media site (e.g., Facebook, Instagram, X (formerly Twitter), YouTube, TikTok, etc.) from the time of enrollment until they are notified that the study is completed.
Key Exclusion Criteria:
- Must not have any clinically significant abnormalities in medical history (e.g., major surgery within 3 months of screening), or on physical examination for which treatment with an antisense oligonucleotide (ASO) would be contraindicated or which, in the opinion of the Principal Investigator (PI), could confound the results of this study.
- Known brain or spinal disease that would interfere with the lumbar puncture (LP) procedure, cerebrospinal fluid (CSF) circulation, or presence of other factors would affect the safety of the LP procedure.
- Must not have any other conditions, which, in the opinion of the Investigator, would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study.
- Must not have any laboratory abnormalities or any other clinically significant abnormalities that would, as assessed by the Investigator, at screening or Baseline, render a participant unsuitable for inclusion.
- Previous treatment with an oligonucleotide (including small interfering ribonucleic acid (RNA) [siRNA], ASOs) gene therapy or gene editing. This exclusion criterion does not apply to approved nucleic acid-based vaccines, including mRNA vaccines, which are allowed.
- Has molecular confirmation of AS due to paternal uniparental disomy, imprinting center defect, or mosaic findings.
Other inclusion/exclusion criteria may apply.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Cohort 1 obudanersen 80 mg
Participants (aged 2 to <18 years old) will be administered obudanersen 80 mg via intrathecal (IT) injection every 12 weeks during the double blind and LTE treatment periods. |
obudanersen will be administered by IT injection.
다른 이름들:
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위약 비교기: Cohort 1 Placebo
Participants (aged 2 to <18 years old) will be administered obudanersen matching placebo via IT injection every 12 weeks during the double-blind treatment period and then administered obudanersen 40 mg or 80 mg every 12 weeks during the LTE treatment period. |
obudanersen matching placebo will be administered by IT injection. |
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실험적: Cohort 2 obudanersen 80 mg
Participants (aged 18 to ≤50 years old) will be administered obudanersen 80 mg via IT injection every 12 weeks during the double blind and LTE treatment periods. |
obudanersen will be administered by IT injection.
다른 이름들:
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위약 비교기: Cohort 2 Placebo
Participants (aged 18 to ≤50 years old) will be administered obudanersen matching placebo via IT injection every 12 weeks during the double-blind treatment period and then randomized to obudanersen 40 mg or 80 mg every 12 weeks during the LTE treatment period. |
obudanersen matching placebo will be administered by IT injection. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change in Performance on the Expressive Communication Subdomain Raw Score of the Bayley Scales for Infant and Toddler Development-4 (Bayley-4) Without Caregiver Input in Cohort 1
기간: Baseline and Week 52
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The Bayley-4 is a performance-based assessment of developmental functioning across communication, cognition, and motor skills. The expressive communication subdomain of communication measures preverbal and verbal communication. The total raw score reflects the sum of all the item scores within the expressive communication subdomain, with higher scores reflecting greater expressive communication ability. |
Baseline and Week 52
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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치료에 대한 부작용 (TEAES) 및 심각한 부작용 (SAES)을 가진 참가자의 비율
기간: 최대 52 주
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최대 52 주
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활력 징후 및 임상 실험실 결과의 변화
기간: 기준선 및 52 주차
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기준선 및 52 주차
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Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Cognition Subdomain Raw Score Without Caregiver Input
기간: Baseline and Week 52
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The Bayley-4 is a performance-based assessment of developmental functioning across communication, cognition, and motor skills. The cognitive subdomain measures learning, memory and concept formation. The total raw score reflects the sum of all the item scores within the expressive communication subdomain, with higher scores reflecting greater cognitive ability. |
Baseline and Week 52
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Change in Symptoms of Angelman Syndrome -Clinician Global Impression of Change (SAS-CGI-C): Overall AS
기간: Baseline and Week 52
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The SAS-CGI-C for Overall AS is a disease-specific clinician-reported outcome assessment measure for Angelman syndrome. The clinicians rate their overall impression of the change of the participant's Angelman syndrome symptoms utilizing a 7-point scale, ranging from "very much improved" (1) to "very much worse" (7). |
Baseline and Week 52
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Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Receptive Communication Subdomain Raw Score
기간: Baseline and Week 52
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The Vineland-3 assesses adaptive behaviors across 4 domains via a semi-structured interview between a trained clinician and the caregiver of the participant with AS. The receptive communication subdomain of communication measures the participant's ability to attend, understand, and respond appropriately to information from others. The total raw score reflects the sum of all the item scores within the receptive communication subdomain, with higher scores reflecting greater receptive communication ability. |
Baseline and Week 52
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Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Daily Living Skills, Personal Subdomain Raw Score
기간: Baseline and Week 52
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The Vineland-3 assesses adaptive behaviors across 4 domains via a semi-structured interview between a trained clinician and the caregiver of the participant with AS. The Personal subdomain of the Daily Living Skills domain measures the participant's self-sufficiency in such areas as eating, dressing, washing, hygiene, and health care. The total raw score reflects the sum of all the item scores within the Personal subdomain, with higher scores reflecting greater ability. |
Baseline and Week 52
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Change in Symptoms of Angelman Syndrome - Clinician Global Impression of Change (SAS-CGI-C): Sleep Problems
기간: Baseline and Week 52
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The SAS-CGI-C for Sleep Problems is a disease-specific clinician-reported outcome assessment measure for Angelman syndrome. The clinicians rate their overall impression of the change in the participant's sleep problems utilizing a 7-point scale, ranging from "very much improved" (1) to "very much worse" (7). |
Baseline and Week 52
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Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Fine Motor Subdomain Raw Score Without Caregiver Input
기간: Baseline to Week 52
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The Bayley-4 is a performance-based assessment of developmental functioning across communication, cognition, and motor skills. The Fine Motor subdomain of communication measures motor abilities such as reaching, object manipulation, and grasping. The total raw score reflects the sum of all the item scores within the fine motor subdomain, with higher scores reflecting greater fine motor ability. |
Baseline to Week 52
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Change in Observer-Reported Communication Ability (ORCA): Overall Emerging T Score
기간: Baseline and Week 52
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The ORCA measure assesses, from the caregiver's perspective, the communication ability of individuals with neurodevelopmental disorders, like Angelman syndrome. This questionnaire assesses expressive, receptive, and pragmatic communication. The ORCA measure produces a single score that is an estimate of an individual's overall level of communication ability, with higher T-scores reflecting greater communication ability. |
Baseline and Week 52
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공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- ION582-CS2
- 2024-519711-33-00 (씨티스)
- U1111-1319-2765 (기타 식별자: WHO Number)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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