Phase 3 Study of the Efficacy and Safety of ION582 in Children and Adults With Angelman Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 158
- 试验地点
- 55
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: obudanersen (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: obudanersen (Drug)
结局指标
主要结局
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
时间窗: Baseline and Week 52
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.
次要结局
- Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Receptive Communication Subdomain Raw Score(Baseline and Week 52)
- Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Daily Living Skills, Personal Subdomain Raw Score(Baseline and Week 52)
- Change in Symptoms of Angelman Syndrome - Clinician Global Impression of Change (SAS-CGI-C): Sleep Problems(Baseline and Week 52)
- Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Fine Motor Subdomain Raw Score Without Caregiver Input(Baseline to Week 52)
- Change in Observer-Reported Communication Ability (ORCA): Overall Emerging T Score(Baseline and Week 52)
- Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to Week 52)
- Change in Vital Signs and Clinical Laboratory Results(Baseline and Week 52)
- Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Cognition Subdomain Raw Score Without Caregiver Input(Baseline and Week 52)
- Change in Symptoms of Angelman Syndrome -Clinician Global Impression of Change (SAS-CGI-C): Overall AS(Baseline and Week 52)
- Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Receptive Communication Subdomain Raw Score(Baseline and Week 52)
- Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Daily Living Skills, Personal Subdomain Raw Score(Baseline and Week 52)
- Change in Symptoms of Angelman Syndrome - Clinician Global Impression of Change (SAS-CGI-C): Sleep Problems(Baseline and Week 52)
- Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to Week 52)
- Change in Vital Signs and Clinical Laboratory Results(Baseline and Week 52)