A Safety and Efficacy of Intrathecally Administered ION283 in Patients With Lafora Disease

Official title

A Phase 1/2 Open Label Study to Evaluate the Safety and Efficacy of Intrathecally Administered ION283 in Patients With Lafora Disease

Overview

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.

Detailed description

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:

* Screening Period: 4 weeks * Open label Treatment Period: 24 months

Interventions

• Genetic ION283
  Anti-sense Oligonucleotide therapy that includes intrathecal (IT) injections by lumbar puncture (LP) with dose level of 15 mg.

Primary outcome measures

• Safety of ION283 as assessed by the number of participants with Treatment related AEs [Time frame: 2 years]

Secondary outcome measures (12)

• Efficacy of ION283 as measured by Lafora Disease Performance Scale [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by Pediatric Evaluation of Disability Inventory Scale [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by Parent Global Impression of Change Scale [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by Clinical Global Impression of Change Scale [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by Quality of Life in Childhood Epilepsy questionnaire [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by Quality of Life in Epilepsy for Adolescents questionnaire [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by Patient-Weighted Quality of Life in Epilepsy inventory questionnaire [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by change in frequency of seizures from baseline [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by change in EEG recordings from baseline: Background rhythms (posterior dominant rhythm) [Time frame: 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) [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by change in EEG recordings from baseline: Electrographic seizures on EEG [Time frame: Baseline, 2 years]
• Efficacy of ION283 as measured by change in EEG recordings from baseline: Epileptiform discharges [Time frame: Baseline, 2 years]

Eligibility criteria

Inclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Childrens Health — Dallas

Identifiers

NCT: NCT06609889 · STU-2024-0411

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗