Tianasen (ASO-GNAO1) for GNAO1-Encephalopathy With Epilepsy and Movement Disorders.

NCT07363603 | Recruiting Phase 1 DMC

• 1 other identifier: ASO-GNAO1
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of the investigational drug ASO-GNAO1 (Tianasen) in pediatric patients with c.607G\>A mutation in the GNAO1 gene associated with epilepsy and neurodevelopmental disorder. The main questions it aims to answer are:

1. 1.Does intrathecal administration of ASO-GNAO1 slow or halt the progression of motor and cognitive symptoms?
2. 2.Is ASO-GNAO1 safe and well-tolerated in this patient population?
3. 3.What is the appropriate therapeutic dose?

Conditions

GNAO1; Epilepsy; Hyperkinesis

Keywords

GNAO1; Epilepsy; hyperkinesis

Outcome Measures

Primary Outcomes (4)

• Change in monthly seizure frequency

  Change from Baseline in the number of seizure episodes per month. Unit of Measure: seizures per month

  Baseline to Week 50

• Change in total monthly duration of seizures

  Change from Baseline in the total duration of seizure episodes per month. Unit of Measure: minutes per month

  Baseline to Week 50

• Change in frequency of non-epileptic hyperkinetic and dystonic episodes

  Change in frequency of non-epileptic hyperkinetic and dystonic episodes Unit: episodes per month

  Baseline to Week 50

• Change in duration of non-epileptic hyperkinetic and dystonic episodes

  Change in duration of non-epileptic hyperkinetic and dystonic episodes Unit: minutes per month

  Baseline to Week 50

Secondary Outcomes (6)

• Change in epileptiform activity index on EEG

  Baseline, Week 46

• Change in Barry-Albright Dystonia Scale score

  Baseline, Week 46

• Change in concomitant medication dosages

  Baseline, Week 46

• Change in Gross Motor Function Measure-88 total score

  Baseline, Week 46

• Change in Denver Developmental Screening Test developmental age

  baseline and week 46

Study Arms (1)

GNAO1 c.607G>A carriers

EXPERIMENTAL

Patients enrolled based on the screening results will receive intrathecal administration of the ASO drug Tianasen, starting with a minimum initial dose of 0.3 mg/kg. The drug dose will be escalated every 2 weeks until the expected therapeutic dose of 1.2 mg/kg is reached. With good tolerability, the dose may be further increased to 1.5 mg/kg. Upon reaching the final dose level, an interim analysis of the results from the dose escalation period (including PK, efficacy, and safety assessments) will be conducted. Based on the results of this analysis, a decision will be made regarding the continuation of the study using the achieved dose. The study may be terminated prematurely if the risk-benefit ratio is deemed unfavorable.

Biological: Antisense oligonucleotide treatment (ASO)

Interventions

Antisense oligonucleotide treatment (ASO) BIOLOGICAL

Intrathecal escalating doses from 0.3 mg/kg to 1.5 mg/kg (single administration per dose level)

Also known as: Tianasen

GNAO1 c.607G>A carriers

Eligibility Criteria

• Age: 1 Year - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Informed Consent: Written informed consent from the parent(s) or legal guardian(s) of the patient and the child's assent (where applicable based on age and cognitive ability), obtained prior to the initiation of any study-related procedures.
• Age: Male or female children aged 1 year and older (≥1 year) until 14 years at the time of informed consent signing.
• Diagnosis: A confirmed a c.607G\>A variant in of GNAO1 gene based on genetic testing, and a clinical presentation that includes both epilepsy and movement disorders.
• Treatment Resistance:
• For seizures: Documented resistance to antiseizure medications prior to screening, defined as the persistence of seizures despite adequate trials of at least two appropriately dosed antiseizure medications.
• For non-epileptic hyperkinesias/dystonia: Documented resistance to anti-hyperkinetic medications prior to screening, defined as the persistence of debilitating hyperkinesias or dystonic attacks despite adequate trials of at least two appropriately dosed anti-hyperkinetic medications.
• Contraception (for females of reproductive potential): For post- menarche female adolescents, a negative serum or urine pregnancy test at screening and agreement to use highly effective methods of contraception (e.g., hormonal implants, combined oral contraceptives, intrauterine device) throughout the study participation period.

You may not qualify if:

• Unacceptable Risk: Any concurrent severe medical, neurological, or psychiatric condition, or any other significant circumstance (e.g., unstable clinical status) that, in the judgment of the Investigator, could significantly increase the risk associated with study participation or the administration of the investigational product, or could interfere with the interpretation of study results.
• Impossibility of Intervention: Any anatomical abnormality, coagulation disorder, active infection, or other condition that constitutes a contraindication to or precludes the safe performance of repeated lumbar punctures for intrathecal administration of the study drug.
• Pregnancy or Lactation: Pregnancy, lactation, or intention to become pregnant during the study period.
• Concurrent Experimental Therapy: Receipt of any other investigational drug, device, or biological product within 1 month prior to screening or within a period of at least 5 half-lives of that product (whichever is longer).
• Protocol Compliance: Any other disease, condition, or behavioral factor that, in the opinion of the Investigator, could compromise the patient's safety, preclude adherence to the protocol schedule, or interfere with the study conduct and endpoint assessments. Age: 14 years and older

Sponsors & Collaborators

• Pirogov Russian National Research Medical University: lead

Study Sites (1)

Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University

Moscow, Russia

RECRUITING

MeSH Terms

Conditions

Epilepsy; Hyperkinesis

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Elena D Belousova, Prof

  Pirogov Russian National Research Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Artem A Sharkov

CONTACT

+7 (499) 487-54-51; a.sharkov@pedklin.ru

Study Design

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

Study Record Dates

• First Submitted: September 29, 2025
• First Posted: January 23, 2026
• Study Start: September 9, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 23, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: immediately after the publication of the final article in a peer-reviewed journal and ending 3 years after the publication of results
• Access Criteria: Access to de-identified IPD will be granted to researchers affiliated with academic or scientific research institutions, as well as to representatives of pharmaceutical companies, provided that the request is approved by the study's Scientific Steering Committee. Applicants must submit a formal request to bv@mda-cro.com. The request must include a detailed description of the research question, analysis plan, required set of variables, and timeline. The Committee's decision will be based on the scientific merit of the proposal, the ethical nature of the objectives, and data availability. Approved applicants will be required to sign a Data Transfer Agreement (DTA), which obligates them to use the data solely for the stated purpose, not to attempt to re-identify participants, to ensure data security, and to acknowledge the original source in any publications. The analysis must be conducted in accordance with the pre-approved statistical plan.

Locations

RU (1)