Natural History and Functional Status Study of Patients With Lafora Disease

• ClinicalTrials.gov Identifier: NCT03876522
• Recruitment Status: Completed
• First Posted: March 15, 2019
• Last Update Posted: September 28, 2022
• Sponsor: Ionis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Ionis Pharmaceuticals, Inc.

Study Description

Brief Summary:

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.

Condition or disease
Lafora Disease

Study Design

• Study Type: Observational
• Actual Enrollment: 33 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Prospective, Longitudinal, Observational Study of the Natural History and Functional Status of Patients With Lafora Disease
• Actual Study Start Date: January 9, 2019
• Actual Primary Completion Date: April 1, 2022
• Actual Study Completion Date: April 1, 2022

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

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

Biospecimen Retention:   Samples With DNA

Blood samples will be collected and used for evaluations of potential biomarkers of Lafora disease progression.

Cerebral spinal fluid (CSF) samples will be collected and used for safety evaluations and assessments of potential biomarkers of Lafora disease progression.

Eligibility Criteria

• Ages Eligible for Study: 5 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Global Lafora patient population

Criteria

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.

Contacts and Locations

Locations

United States, California

IONIS Investigative Site

Los Angeles, California, United States, 90095

United States, Texas

IONIS Investigative Site

Dallas, Texas, United States, 75390

Italy

IONIS Investigative Site

Bologna, Italy

Spain

IONIS Investigative Site

Madrid, Spain

Sponsors and Collaborators

Ionis Pharmaceuticals, Inc.

More Information

• Responsible Party: Ionis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03876522
• Other Study ID Numbers: LAF-NHS
• First Posted: March 15, 2019
• Last Update Posted: September 28, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ionis Pharmaceuticals, Inc.:

Lafora Disease; EPM2A; EPM2B; Myoclonus epilepsy; Myoclonic seizures; Glycogen storage disease

Additional relevant MeSH terms:

Lafora Disease; Myoclonic Epilepsies, Progressive; Epilepsies, Myoclonic; Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn