NCT06609889招募中1 期
A Phase 1/2 Open Label Study to Evaluate the Safety and Efficacy of Intrathecally Administered ION283 in Patients With Lafora Disease
Berge Minassian2 个研究点 分布在 1 个国家目标入组 10 人开始时间: 2024年12月3日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Safety of ION283 as assessed by the number of participants with Treatment related AEs
研究概览
简要总结
This study will test the safety and efficacy of multiple doses of ION283 administered as intrathecal (IT) injections by lumbar puncture (LP). All subjects will receive ION283. The dose level of 15 mg will be studied in all subjects.
详细描述
A Phase 1/2 Open Label Study to Evaluate the Safety and Efficacy of Intrathecally Administered ION283 in Patients with Lafora Disease
A single cohort will be evaluated in the study:
N=10
• Initial dose of 15 mg ION283 intrathecal bolus (ITB) injection every 12 weeks.
The study consists of 2 periods:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •General Inclusion Criteria
- •Must give written informed consent (and assent if indicated by patient's age and in accordance with local requirements) and be willing/able to comply with all study requirements.
- •Aged 10-18 (inclusive) years old at the time of informed consent.
- •Non-pregnant and non-lactating females
- •All male participants and women of childbearing potential must refrain from sperm/egg donation from the time of signing the informed consent/assent form until at least 12 weeks (approximately 5 half-lives of ION283) after the dose of Study Drug.
- •For participants engaged in sexual relations of childbearing potential, highly effective contraception must be used from the time of signing the informed consent/assent form until at least 12 weeks (approximately 5 half-lives of ION283) after receiving Study Drug.
- •Target Inclusion Criteria
- •Genetically confirmed diagnosis of Lafora disease before or at enrollment (documented pathogenic mutations in known causative genes (EPM2A/laforin, EPM2B/NHLRC1/malin)
- •Must have LDPS score ≥ 9 and LDPS motor subscore of ≥ 2 (independent ambulation- walking 10 steps independently)
- •Exclusion Criteria
- •Clinically significant abnormalities in medical history (e.g., previous stroke within 6 months of Screening, major surgery within 3 months of Screening) or physical examination
- •Platelet count < 80,000/mm3 or any other clinically significant laboratory abnormalities that would render a patient unsuitable for inclusion.
- •History of bleeding diathesis or coagulopathy
- •Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
- •Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
- •Contraindication or unwillingness to undergo lumbar puncture
- •Known history of, or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
- •Moderate-to-severe hepatic impairment or renal impairment.
- •Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix that has been successfully treated or benign pediatric tumors. Patients with a history of other malignancies that have been treated with curative intent and which have no recurrence within 5 years may also be eligible if approved by the Sponsor's Medical Monitor
- •Uncontrolled hypertension defined as:
- •for patients < 13 years old, BP ≥ 95th percentile + 12 mmHg, or ≥ 140/90 mmHg, whichever is lower for patients ≥ 13 years old, BP ≥ 140/90 mmHg
- •Previous treatment with an oligonucleotide (including small interfering ribonucleic acid [siRNA]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received; or history of hypersensitivity to ION283 or its excipients; or history of hypersensitivity to any ASO. This exclusion criterion does not apply to COVID-19 mRNA vaccinations
- •History of alcohol or drug abuse within 12 months of Screening, or current drug or alcohol abuse
- •Has enrolled in any clinical trial or used any investigational agent or device, or has participated in any investigational procedure, within the 30 days, or within 5 half-lives of investigational agent, whichever is longer, before screening or does so concurrently with this study
- •Use of antiplatelet or anticoagulant therapy within the 14 days prior to Screening (with the exception of aspirin ≤ mg/day) or anticipated use during the study, including but not limited to clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, and apixaban
排除标准
- 未提供
结局指标
主要结局
Safety of ION283 as assessed by the number of participants with Treatment related AEs
时间窗: 2 years
Safety of ION283 will be assessed by the number of participants with Treatment related Adverse Events (AEs) which will be listed according to the severity (mild, moderate, severe) as assessed by the Investigator. A dose limiting toxicity (DLT) is defined as any ≥ Grade 3 (severe, life-threatening, disabling, or fatal) AND related to the Study Drug. The occurrence of (i) DLTs in 2 patients following administration or (ii) a single serious adverse event (SAE) that is life threatening and related to Study Drug will result in termination of further dosing and the dose tested will be considered to be dose limiting.
次要结局
- Efficacy of ION283 as measured by Lafora Disease Performance Scale(Baseline, 2 years)
- Efficacy of ION283 as measured by Pediatric Evaluation of Disability Inventory Scale(Baseline, 2 years)
- Efficacy of ION283 as measured by Parent Global Impression of Change Scale(Baseline, 2 years)
- Efficacy of ION283 as measured by Clinical Global Impression of Change Scale(Baseline, 2 years)
- Efficacy of ION283 as measured by Quality of Life in Childhood Epilepsy questionnaire(Baseline, 2 years)
- Efficacy of ION283 as measured by Quality of Life in Epilepsy for Adolescents questionnaire(Baseline, 2 years)
- Efficacy of ION283 as measured by Patient-Weighted Quality of Life in Epilepsy inventory questionnaire(Baseline, 2 years)
- Efficacy of ION283 as measured by change in frequency of seizures from baseline(Baseline, 2 years)
- Efficacy of ION283 as measured by change in EEG recordings from baseline: Background rhythms (posterior dominant rhythm)(Baseline, 2 years)
- Efficacy of ION283 as measured by change in EEG recordings from baseline: Background rhythms ( normal versus abnormal sleep physiology to include presence of sleep spindles)(Baseline, 2 years)
- Efficacy of ION283 as measured by change in EEG recordings from baseline: Electrographic seizures on EEG(Baseline, 2 years)
- Efficacy of ION283 as measured by change in EEG recordings from baseline: Epileptiform discharges(Baseline, 2 years)
研究者
Berge Minassian
Professor & Division Chief (Pediatrics-Neurology)
University of Texas Southwestern Medical Center
研究点 (2)
Loading locations...
相似试验
招募中
1 期
Study to Assess Safety and Tolerability of Multiple Doses of EO2002Corneal EdemaCorneal Endothelial DystrophyEndothelial DysfunctionFuchs DystrophyFuchs' Endothelial DystrophyBullous KeratopathyPseudophakic Bullous KeratopathyCorneal Edema PseudophakicNCT05636579Asociación para Evitar la Ceguera en México12
已完成
2 期
A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD in Cystic Fibrosis Patients With at Least 1 G542X AlleleCystic FibrosisNCT04126473Eloxx Pharmaceuticals, Inc.17
已完成
2 期
A Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose in Previously Vaccinated Participants and Unvaccinated Participants.COVID-19NCT05975060Novavax660
已完成
2 期
A Study to Assess Vamorolone in Boys Ages 2 to <4 Years and 7 to <18 Years With Duchenne Muscular Dystrophy (DMD)Duchenne Muscular DystrophyNCT05185622Santhera Pharmaceuticals54
已完成
2 期
Efficacy and Safety of Gemcabene in Patients With Homozygous Familial Hypercholesterolemia on Stable, Lipid-Lowering Therapy (COBALT-1)HypercholesteremiaNCT02722408NeuroBo Pharmaceuticals Inc.8