REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome
ConditionAngelman Syndrome
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age2-50
SponsorIonis Pharmaceuticals, Inc.
About this trial
The purpose of this study is to evaluate the efficacy and safety of ION582 in children and adults with Angelman syndrome caused by a deletion or mutation of the UBE3A gene.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
ION582
DrugION582 will be administered by IT injection.
Placebo
DrugION582 matching placebo will be administered by IT injection.
Treatment groups
158 Participants
are divided into 4 treatment groupsGroup A: Cohort 1 ION582 80 mgExperimental treatment 1 intervention
Group B: Cohort 1 PlaceboPlacebo comparator 1 intervention
Group C: Cohort 2 ION582 80 mgExperimental treatment 1 intervention
Group D: Cohort 2 PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
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
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.
Time frame
Baseline and Week 52Secondary outcomes
1
Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Cognition Subdomain Raw Score Without Caregiver Input
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.
Time frame
Baseline and Week 522
Change in Symptoms of Angelman Syndrome -Clinician Global Impression of Change (SAS-CGI-C): Overall AS
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).
Time frame
Baseline and Week 523
Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Receptive Communication Subdomain Raw Score
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.
Time frame
Baseline and Week 524
Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Daily Living Skills, Personal Subdomain Raw Score
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.
Time frame
Baseline and Week 52Sponsors and contacts
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Source ClinicalTrials.gov