Intrathecal Gene Therapy For SLC13A5 Citrate Transporter Disorder

Not Applicable

Not yet recruiting

• Conditions: SLC13A5 Citrate Transporter Disorder
• Interventions: Drug: TSHA-105

• Registration Number: NCT07102524
• Lead Sponsor: TESS Research Foundation

Brief Summary

Phase 1/2, open-label study to assess the efficacy and safety of a single lumbar intrathecal administration of TSHA-105 in individuals with SLC13A5 Citrate Transporter Disorder

Detailed Description

TSHA-105 is an AAV9-based gene therapy vector that expresses the fully functional form of SLC13A5 under the control of a synthetic promoter. TSHA-105 will be delivered intrathecally and is designed to achieve stable, potentially life-long expression of SLC13A5 protein in non-dividing cells. This clinical study is a pivotal open-label phase 1/2 study designed to assess safety and efficacy of TSHA-105 in individuals with SLC13A5 Citrate Transporter Disorder.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-21
• Study First Submitted QC: 2025-07-28
• Study First Posted: 2025-08-03
• Last Update Submitted: 2025-08-11
• Last Update Posted: 2025-08-14
• Study Start: 2025-12-01
• Primary Completion: 2030-12-01
• Study Completion: 2031-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Male and females between the ages of 2 to 9 and 10 to 20 years at the time of screening
• Confirmed diagnosis of SLC13A5 citrate transporter disorder by genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, confirmed pathogenic variants in the SLC13A5 gene
• Clinical features consistent with SLC13A5 citrate transporter disorder
• Written informed consent provided by subject/parent/guardian and willingness to participate and comply with all the study related visits and procedures. Assent provided by children 10 to 17 years old based on their ability to understand the risks and possible benefits, and the activities expected of them.
• Subjects able to reproduce must use a barrier method of contraception for the first 12 months after dosing as well as at least one additional highly effective birth control method if sexually active

Exclusion Criteria

• Inability to participate in study procedures (as determined by the site investigator)
• Presence of a concomitant medical condition that precludes lumbar puncture (LP) or use of anesthetics
• History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy
• Inability to be safely sedated in the opinion of the clinical anesthesiologist
• Active infection, at the time of dosing, based on clinical observations
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
• Inability of the subject to undergo MRI according to local institutional policy
• Inability of the subject to undergo any other procedure required in this study
• The presence of significant non-SLC13A5 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
• Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
• Enrollment and participation in another interventional clinical trial
• Contraindication to TSHA-105 or any of its ingredients
• Contraindication to any of the immune suppression medications used in this study
• Clinically significant abnormal laboratory values (hemoglobin < 6 or > 20 g/dL; white blood cell > 20,000 per cmm, platelets count < 100,000 per cmm; INR > ULN; GGT, ALT, and AST or total bilirubin > 2x ULN, creatinine ≥ 1.5 mg/dL) prior to gene replacement therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TSHA-105 treament	TSHA-105	TSHA-105 Treatment

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability	5 years	Safety measured by: * Incidence of AEs/SAEs considered related to TSHA-105 and grade 3 or higher as per the Common Terminology Criteria for Adverse Events through month 24; * Clinical Safety Labs (Chemistry, Hematology, Coagulation, Lipids, Cardiac Safety, Urinalysis), Vital Signs, EKGs, Trans-thoracic Echocardiogram

Secondary Outcome Measures

Name	Time	Method
Peabody Developmental Motor Scales, 2nd Edition	5 Years	Assesses fine and gross motor skills in children from birth to 5 years.; Subtests include reflexes, locomotion, object manipulation, grasping, and visual-motor integration.
Mullens Scales of Early Learning	5 Years	Evaluates cognitive and motor development in children from birth to 68 months.; Measures visual reception, fine motor, expressive language, and receptive language.
SLC13A5 Deficiency Movement Assessment Scale	5 years	A disease-specific tool developed to evaluate motor function and movement abnormalities in children with SLC13A5 deficiency
Vineland Adaptive Behavior Scale, 3rd Edition	5 years	Measures adaptive behaviors including communication, daily living skills, socialization, and motor skills.
PedsQL Family Impact Module	5 years	Measures the impact of pediatric chronic health conditions on parents and families.; Focuses on emotional, social, and cognitive functioning, as well as communication and worry.
PedsQL Epilepsy Module	5 Years	A disease-specific quality-of-life tool designed for children with epilepsy.; Assesses cognitive functioning, worry, impact, and communication.
Seizure Diary	5 years	A caregiver-completed log for tracking seizure frequency, duration, type, and possible triggers.; For evaluating treatment response and seizure patterns.
Physician Clinical Global Impression (CGI)	5 years	A clinician-rated scale that evaluates illness severity and improvement over time.
Parent-Assessed Clinical Global Impression (PGI)	5 years	A caregiver's subjective assessment of the child's overall functioning and response to treatment
Sleep Disturbance Scale for Children	5 years	A parent-reported tool for assessing sleep problems in children aged 6.5-15 years.; Evaluates disorders like insomnia, sleep-disordered breathing, and excessive somnolence

Trial Locations

Locations (1)

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States