a safety and efficacy of intrathecally administered ion283 in patients with lafora disease

Conditions: Lafora Disease

Summary: 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.

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

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

Keywords: lafora disease