A Study of the Natural Course of SURF1 Deficiency

A Natural History Study of Surfeit Locus Protein 1 (SURF1)-Associated Leigh Syndrome

The purpose of the study is to prospectively and systematically collect standardized clinical information, to describe important features of the disease course of SURF1 deficiency. These include but are not limited to symptomatology, clinical course, and risk factors for severe disease and complications.

Study Overview

• Status: Withdrawn
• Conditions: Leigh Syndrome
• Intervention / Treatment: Other: None (Observational study)

Detailed Description

Participant eligibility for the study will be determined during a screening period lasting up to 45 days. In-clinic follow visits will occur over several days every 6 months for 2 years from baseline. Thereafter, annual telephone follow-up contact will be conducted for 2 additional years. Thus, the active study duration for each participant will be up to approximately 2 years and the total duration per participant will be approximately 4 years.

The study will be conducted in the United States and select sites outside the United States based on incidence data.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UTSW Medical Center at Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants with SURF1 deficiency

Description

Inclusion Criteria:

• Informed consent/assent provided by the participant based on participant's cognitive ability as determined by Principal Investigator (PI), and/or participant's parent(s) or legally authorized representative(s).
• Participant is < 18 years of age at time of initial informed consent.
• Displays one or more clinical features consistent with SURF1 deficiency, including but not limited to, hypotonia, motor delays, motor regression, failure to thrive, language delays, and/or language regression.
• Genetic diagnosis of SURF1 pathogenic or likely pathogenic mutation(s), either compound heterozygous or homozygous mutations. If variants are of uncertain significance (VUS), verify documentation of cytochrome c oxidase (COX) activity deficiency.
• Ability to travel to the study site and adhere to study-related follow-up examinations and/or procedures and provide access to participant's medical records.

Exclusion Criteria:

• Any known genetic abnormality (other than SURF1 deficiency), including but not limited to a chromosomal aberration or molecularly known or clinically suspected progressive neurometabolic disorder or dementia, that confounds the clinical phenotype.
• The presence of significant non-SURF1-related central nervous system (CNS) impairment/behavioral disturbances that would confound the scientific rigor or interpretation of results of the study or a known history of perinatal asphyxia, kernicterus, carbon monoxide or methanol intoxication.
• Current participation in a therapeutic study or participation in a therapeutic study within 30 days prior to enrollment in the present study.
• Prior or current treatment with gene or stem cell therapy.
• Any condition that, in the opinion of the Site Investigator, could put the participant at undue risk and/or would ultimately prevent the completion of study procedures.

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	Intervention / Treatment
Prospective cohort; Parents/caregivers of participants with SURF1 deficiency will provide information regarding diagnosis, onset of symptoms, and course of the disease and participants will be assessed prospectively over time using standardized qualitative and quantitative tools.	Other: None (Observational study); No investigational intervention, marketed product, or placebo will be administered to study participants in this study.; Other Names: Observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS)	The NPMDS is scored by section (domain), and the final (total) score is the sum of all section scores. Function is rated over preceding 4-week period, according to participant and/or caregiver. NPMDS is subdivided by patient age (0-24 months, 2-11 years, and 12-18 years).	From baseline until follow-up (up to 24 months/early termination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Head Control Scale	Head control will be evaluated using the Head Control Scale (which ranges 0 to 16, with 0 representing no function and 4 representing normal function in each of the 4 domains).	From baseline until follow-up (up to 24 months/early termination)
Change from baseline in Gross Motor Function Measure (GMFM)	The Gross Motor Function Measure will measure the child's capacity for gross motor function. Scores are based on a 0 to 100% scale with higher percentage indicating better function.	From baseline until follow-up (up to 24 months/early termination)
Change from baseline in Vineland Adaptive Behavior Scales Third Edition (Vineland-3)	Vineland-3 forms aid in diagnosing and classifying intellectual and developmental disabilities and other disorders. The individual's overall adaptive functioning is described by a total score and three subdomain scores. The scores ranges from 20 to 140, with higher numbers indicating better performance.	From baseline until follow-up (up to 24 months/early termination)

Collaborators and Investigators

• Sponsor: Taysha Gene Therapies, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2022
• Primary Completion (Actual): May 4, 2022
• Study Completion (Actual): May 4, 2022

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: March 3, 2022
• First Posted (Actual): March 14, 2022

Study Record Updates

• Last Update Posted (Actual): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Biomarkers; Leigh Syndrome; Neurodegenerative disease; Primary Mitochondrial Disease; SURF1-associated Leigh Syndrome; Epidemiology study; Genotype-phenotype correlation data; SURF1 deficiency; Natural History study
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Mitochondrial Diseases; Brain Diseases, Metabolic, Inborn; Pyruvate Metabolism, Inborn Errors; Syndrome; Leigh Disease
• Other Study ID Numbers: TSHA-104-RG-001

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