A Phase I/II, First-In-Human Trial to Evaluate the Safety, Tolerability, and Pharmacokinetic Activity to Prevent or Treat Neuropsychiatric Symptoms in Pediatric Subjects With Timothy Syndrome

NCT07600658 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 86899
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if an antisense oligonucleotide (TS1-ASO) can safely treat and potentially prevent neuropsychiatric and neurodevelopmental symptoms in pediatric participants (age \>2 months) with Timothy Syndrome Type 1 (TS1). The main questions it aims to answer are:

1. 1.Is TS1-ASO safe and well tolerated when administered intrathecally in children with TS1?
2. 2.What are the pharmacokinetics and preliminary efficacy of TS1-ASO on neurodevelopmental and neurologic outcomes?
3. 3.Receive intrathecal injections of TS1-ASO via lumbar puncture using a stepwise dose-escalation approach
4. 4.Undergo safety monitoring including neurologic exams, cardiac monitoring, laboratory testing, and adverse event assessments
5. 5.Provide cerebrospinal fluid (CSF) and blood samples for pharmacokinetic and biomarker analyses
6. 6.Complete neurodevelopmental, behavioral, and functional assessments (e.g., adaptive behavior, motor function, communication, seizure tracking) over time

Conditions

CACNA1C

Keywords

Antisense oligonucleotide; Timothy Syndrome

Outcome Measures

Primary Outcomes (1)

• Incidence, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs) from first dose through 12 months of treatment and follow-up.

  Safety and tolerability of TS1-ASO will be evaluated by systematic collection and analysis of AEs and SAEs following intrathecal administration. Events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and assessed for severity, seriousness, and relationship to study drug and procedure. Safety assessments include continuous cardiac monitoring (telemetry), serial electrocardiograms, neurologic examinations, and routine laboratory evaluations (hematology, chemistry, coagulation, and urinalysis). Procedure-related safety (e.g., lumbar puncture complications), neurologic status, and potential class-related effects of antisense oligonucleotides will be closely monitored. Data will be summarized descriptively to characterize the overall safety profile of TS1-ASO in this population.

  From the first dose through 12 months of treatment and follow-up.

Secondary Outcomes (8)

• Pharmacokinetic (PK) profile of TS1-ASO in cerebrospinal fluid (CSF).

  From first dose through 12 months of treatment

• Pharmacokinetic (PK) profile of TS1-ASO in plasma.

  From first dose through 12 months of treatment

• Change in CACNA1C exon 8/8A splicing in CSF

  From Baseline through 12 months.

• Seizure frequency (in participants with epilepsy)

  From Baseline through 12 months.

• Change in adaptive behavior (Vineland Adaptive Behavior Scales Third Edition - Vineland-3)

  From Baseline through 12 months.

Study Arms (1)

TS1-ASO Arm

EXPERIMENTAL

TS1-ASO Drug Administration

Drug: TS1-ASO

Interventions

TS1-ASO DRUG

Antisense oligonucleotide targeting CACNA1C exon 8A/8 splicing

TS1-ASO Arm

Eligibility Criteria

• Age: 2 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed CACNA1C c.1216 G\>A, p.G406R variant in exon 8A (TS1) on exome or genome testing.
• Age \> 2 months. Given that neurodevelopmental symptoms start early in TS1 and treatment is predicted to more effectively prevent rather than rescue developmental delay, ASD, and epilepsy, the Sponsor proposes that early treatment is most likely to yield clinical benefit.

You may not qualify if:

• Critical illness including cardiac arrhythmia that is unstable, invasive ventilatory support, sustained hypoglycemia, or active infection.
• Diagnosis of a secondary genetic disorder in addition to TS1.
• Hypoxic-ischemic injury to \>25% of the brain from prior cardiac arrest.
• Age \> 5 years old with absence of any neurologic, developmental, or psychiatric diagnoses, or symptoms on physical exam and intake assessment scales as there would unlikely be a benefit to treatment in the setting of normal cognition and development and lack of epilepsy or other neuropsychiatric diagnoses.
• Inability to complete required procedures including anesthesia, magnetic resonance imaging brain, and lumbar puncture (LP).
• Participation in another investigational trial within the 90 days prior to first dose, including any gene therapy within the participant's lifetime.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Timothy syndrome

Study Officials

• Sergiu Pasca, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sergiu Pasca, MD

CONTACT

(650) 497-5922; spasca@stanford.edu

Grant Wells

CONTACT

650-714-4344; gwells2@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2026
• First Posted: May 22, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: De-identified individual participant data will be made available beginning 6 months after publication of the primary study results and will remain available for a period of 5 years following publication.
• Access Criteria: Access to de-identified individual participant data (IPD) and supporting documentation will be granted to qualified researchers, including academic investigators and collaborators, who submit a methodologically sound research proposal that is aligned with the scientific objectives of the study and approved by the study sponsor. Researchers will be able to access de-identified datasets underlying published results, including safety data (adverse events, laboratory values), pharmacokinetic and pharmacodynamic data, and key clinical outcome measures, along with supporting materials such as the study protocol, statistical analysis plan, and data dictionaries. Access will be provided through a secure data-sharing mechanism following execution of a data use agreement (DUA) that outlines conditions for data protection, confidentiality, and appropriate use.

Locations

US (1)