Natural History and Functional Status Study of Patients With Lafora Disease

Prospective, Longitudinal, Observational Study of the Natural History and Functional Status of Patients With Lafora Disease

A natural history and functional status study to characterize the clinical disease course in Lafora disease patients using standardized, quantitative evaluations and to identify useful biomarkers and clinical outcome measures for use in future Lafora treatment studies.

Study Overview

• Status: Completed
• Conditions: Lafora Disease

• Study Type: Observational
• Enrollment (Actual): 33

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy
    • Ionis Investigative Site
• Spain
  • Madrid, Spain
    • Ionis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Ionis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Ionis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Global Lafora patient population

Description

Inclusion Criteria:

1. Documented genetic diagnosis of Lafora disease based on mutations in both alleles of either the EPM2A or the EPM2B gene and a sibling with a known mutation in EPM2A or EPM2B.

2. Able and willing to comply with the study protocol, including travel to Study Center, procedures, measurements and visits, including:

   1. Adequately supportive psychosocial circumstances, in the opinion of the Investigator
   2. Caregiver/trial partner committed to facilitate patient's involvement in the study who is reliable, competent, at least 18 years of age.
   3. Adequate visual and auditory acuity for neuropsychological testing

Exclusion Criteria:

1. Any known genetic abnormality, including chromosomal aberrations that confound the clinical phenotype

2. Subjects with:

   1. complete absence of speech OR
   2. inability to perform any activities of daily living OR
   3. who are completely bedridden.
3. Current participation in an interventional or therapeutic study
4. Receiving an investigational drug within 90 days of the Baseline Visit
5. Prior or current treatment with gene or stem cell therapy
6. Any other diseases which may significantly interfere with the assessment of Lafora disease.
7. Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Lafora Disease Patients; Documented genetic diagnosis of Lafora disease; clinical diagnosis of Lafora disease and a sibling with a known mutation in EPM2A or EPM2B; clinical diagnosis of Lafora disease and a previously undescribed mutation in EPM2A or EPM2B; asymptomatic siblings if mutation positive prior to enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes over time in symptom-directed physical exams, measured by height assessment		24 Months
Changes over time in symptom-directed physical exams, measured by weight assessment		24 Months
Changes over time in symptom-directed physical exams, measured by head, eyes, ears, nose, and throat assessment (HEENT)		24 Months
Changes over time in symptom-directed physical exams, measured by cardiovascular assessment		24 Months
Changes over time in symptom-directed physical exams, measured by musculoskeletal assessment		24 Months
Changes over time in symptom-directed physical exams, measured by respiratory assessment		24 Months
Changes over time in symptom-directed physical exams, measured by abdomen assessment		24 Months
Changes over time in symptom-directed physical exams, measured by skin findings		24 Months
Changes in disease-related symptoms over time assessed by the Lafora Disease Performance Scale		24 Months
Seizure frequency, (by type and severity) as recorded in seizure diary		24 Months
Seizure duration, as measured by awake video EEG	EEG measured by background activity awake presence of slow waves	24 Months
Seizure duration, as measured by sleep video EEG	EEG measured by background activity sleep presence of vertex waves	24 Months
Change in disease severity using the Lafora Disease Clinical Performance Scale		24 Months
Change in use of anti-epileptic rescue medication as recorded in seizure diary		24 Months
Intelligence, as measured by the Leiter International Performance Scale		24 Months
Cognitive Function, as measured by Woodcock-Johnson IV Tests of Oral Language		24 Months
Cognitive Function, as measured by Rey Complex Figure Test		24 Months
Cognitive Function, as measured by Children's Orientation and Amnesia Test (COAT)		24 Months
Cognitive Function, as measured by Beery Buktenica Developmental Test of Visual Motor Integration		24 Months
Cognitive Function, as measured by Children's Color Trails Test		24 Months
Motor function, as measured by Gait Analysis		24 Months
Caregiver Ratings, as measured by Vineland-II and Burden Scale of Family Caregivers (short form)		24 Months
Disability, as rated by Pediatric Evaluation of Disability Inventory (PEDI)		24 Months
Ataxia, as measured by the Scale of Assessment and Rating of Ataxia (SARA)		24 Months
Motor function, as measured by Six-Minute Walk Test (6MWT)		24 Months
Motor function, as measured by Timed Up and Go Test (TUG) in ambulatory patients		24 Months
Motor function, as measured by 9 Hole Pegboard Test		24 Months
Quality of Life (QoL), as measured by QoL in Epilepsy for Adolescents (QOLIE-AD-48) by age at Screening		24 Months
Quality of Life (QoL), as measured by QoL in Epilepsy (QOLIE-31P) by age at Screening		24 Months
Quality of Life (QoL), as measured by QoL in Childhood Epilepsy (QOLCE-55) by age at Screening		24 Months

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2019
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: January 10, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Lafora Disease; EPM2A; EPM2B; Myoclonus epilepsy; Myoclonic seizures; Glycogen storage disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Epilepsy; Myoclonic Epilepsies, Progressive; Epilepsies, Myoclonic; Lafora Disease
• Other Study ID Numbers: LAF-NHS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No