RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-12-01

Study Completion:2028-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06609889

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:10 Years to 18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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. * 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) * 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: * 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	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion 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.
* 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)
* 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:
* 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

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Kristy Riddle, RN, BSN

CONTACT

214-456-9501

LDRecruiting@utsouthwestern.edu

Ben Eckert, BA

CONTACT

LDRecruiting@utsouthwestern.edu

Principal Investigator

Berge Minassian, MD

STUDY_DIRECTOR

UT Southwestern Medical Center

Study Locations (Sites)

Childrens Health

Dallas, Texas, 75235

United States

Collaborators and Investigators

Sponsor: Berge Minassian

Berge Minassian, MD, STUDY_DIRECTOR, UT Southwestern Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-01

Study Completion Date2028-10

Study Record Updates

Study Start Date2024-12-01

Study Completion Date2028-10

Terms related to this study

Keywords Provided by Researchers

Lafora Disease

Additional Relevant MeSH Terms

Lafora Disease