Onthullen: een fase 3 -studie van Ion582 in het Angelman -syndroom
Fase 3 -studie van de werkzaamheid en veiligheid van Ion582 bij kinderen en volwassenen met het Angelman -syndroom
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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 3
Contacten en locaties
Studie Locaties
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Heidelberg, Australië, 3084
- Austin Hospital
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Nedlands, Australië, 6009
- Perth Children's Hospital
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Randwick, Australië, 2031
- Sydney Children's Hospital
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Queensland
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South Brisbane, Queensland, Australië, 4101
- Queensland Children's Hospital
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Edmonton, Canada, T6G 2B7
- University of Alberta Hospital
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Vancouver, Canada, V6H 3V4
- British Columbia Children's Hospital
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Ontario
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London, Ontario, Canada, N6A 5W9
- London Health Science Centre - Children's Hospital
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Quebec
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Montreal, Quebec, Canada, H4A 3J1
- McGill University Health Centre
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München, Duitsland, 81377
- Klinikum der Ludwig-Maximilians-Universitaet Muenchen
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Ramat Gan, Israël, 5265601
- Sheba Medical Center
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Milan, Italië, 20133
- Fondazione IRCCS Istituto Neurologico Carlo Besta
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Pisa, Italië, 56126
- Azienda Ospedaliero Universitaria Pisana
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Roma, Italië, 00165
- Ospedale Pediatrico Bambino Gesù
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Osaka
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Izumi, Osaka, Japan, 594-1101
- Osaka Women's and Children's Hospital
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Tokyo
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Kodaira, Tokyo, Japan, 187-8551
- National Center of Neurology and Psychiatry
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Gdansk, Polen, 80-952
- Uniwersyteckie Centrum Kliniczne
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Singapore, Singapore, 229899
- KK Women's and Children's Hospital
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Barcelona, Spanje, 08950
- Hospital Sant Joan de Deu
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Sabadell, Spanje, 08208
- Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
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London, Verenigd Koninkrijk, WC1N 3JH
- Great Ormond Street Hospital for Children - NHS Foundation Trust
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Oxford, Verenigd Koninkrijk, OX3 9DU
- John Radcliffe Hospital
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California
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Los Angeles, California, Verenigde Staten, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, Verenigde Staten, 90095
- UCLA Clinical & Translational Research Center (CTRC)
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San Diego, California, Verenigde Staten, 92123
- Rady Children's Hospital
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Colorado
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Aurora, Colorado, Verenigde Staten, 80045
- Colorado Children's Hospital Research Institute
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District of Columbia
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Washington D.C., District of Columbia, Verenigde Staten, 20011
- Children's National Hospital
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Florida
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Miami, Florida, Verenigde Staten, 33155
- Nicklaus Children's Hospital
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30329
- Children's Healthcare of Atlanta
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Illinois
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Chicago, Illinois, Verenigde Staten, 60612
- Rush University Medical Center
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02115
- Boston Children's Hospital
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Missouri
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Kansas City, Missouri, Verenigde Staten, 64108
- Children's Mercy
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New York
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New York, New York, Verenigde Staten, 10032
- Columbia University Irving Medical Center
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New York, New York, Verenigde Staten, 10029
- Ichan School of Medicine at Mount Sinai
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North Carolina
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Carrboro, North Carolina, Verenigde Staten, 27510
- University of North Carolina at Chapel Hill School of Medicine
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Ohio
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Cincinnati, Ohio, Verenigde Staten, 45229
- Cincinnati Children's Hospital
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Columbus, Ohio, Verenigde Staten, 43205
- Nationwide Children's Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Verenigde Staten, 19104
- Children's Hospital of Philadelphia
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Tennessee
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Nashville, Tennessee, Verenigde Staten, 37232
- Vanderbilt Clinical Research Center
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Texas
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Houston, Texas, Verenigde Staten, 77030
- Texas Children's Hospital
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Seoul, Zuid -Korea, 03080
- Seoul National University Hospital
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Seoul, Zuid -Korea, 06351
- Samsung Medical Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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.
Andere namen:
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Placebo-vergelijker: 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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Experimenteel: 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.
Andere namen:
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Placebo-vergelijker: 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. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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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
Tijdsspanne: 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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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Percentage deelnemers met bijwerkingen voor behandelingsopkomst (Teaes) en ernstige bijwerkingen (SAE's)
Tijdsspanne: Tot week 52
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Tot week 52
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Verandering van vitale tekenen en klinische laboratoriumresultaten
Tijdsspanne: Basislijn en week 52
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Basislijn en week 52
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Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Cognition Subdomain Raw Score Without Caregiver Input
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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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Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- ION582-CS2
- 2024-519711-33-00 (Ctis)
- U1111-1319-2765 (Andere identificatie: WHO Number)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
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/.
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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