Tianasen (ASO-GNAO1) treatment for children with GNAO1-related epilepsy and movement problems

An Open-Label, Non-Randomized Study to Evaluate the Efficacy and Safety of ASO-GNAO1 (Tianasen) in Patients With GNAO1-Encephalopathy With Epilepsy and Movement Disorders Following Repeated Intrathecal Dose Escalation.

Tianasen is being tried as an antisense drug given into the spine to see if it helps children with the GNAO1 c.607G>A mutation who have epilepsy and disabling movement disorders.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 1 Year to 14 Years
• Sex: All
• Sponsor: Pirogov Russian National Research Medical University (Academic / other)
• Locations: 1 site (Moscow)
• Trial ID: NCT07363603 on ClinicalTrials.gov

What this trial studies

This open-label, phase 1/2 dose-escalation study gives allele-specific antisense oligonucleotide (ASO-GNAO1, Tianasen) by intrathecal injection to pediatric patients over a 12-month period. All participants receive the active drug and undergo frequent neurological exams, biomarker testing, and safety monitoring to determine tolerability and an appropriate therapeutic dose. The investigational ASO is designed to selectively suppress the mutant GNAO1 mRNA (c.607G>A) while sparing the wild-type allele, based on in vitro data showing ~85% mutant suppression. The trial is single-center and focuses on children with both drug-resistant epilepsy and hyperkinetic movement disorders caused by the specified GNAO1 variant.

Who should consider this trial

Good fit: Children aged 1 to 14 with a confirmed c.607G>A GNAO1 variant and clinical epilepsy plus movement disorders that have been resistant to standard treatments are the intended participants.

Not a fit: Patients without the c.607G>A GNAO1 variant, those older than the enrollment age range, or those whose symptoms are due to unrelated causes are unlikely to benefit from this allele-specific therapy.

Why it matters

Potential benefit: If successful, Tianasen could reduce seizures, lessen abnormal movements, and slow or halt progression of neurological decline in affected children.

How similar studies have performed: Allele-specific and personalized ASO approaches have precedent (for example Milasen and approved ASOs in other diseases) and ASO-GNAO1 shows promising preclinical allele-specific suppression, but clinical efficacy for this GNAO1 variant is novel and unproven.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Where this trial is running

Moscow

• Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University — Moscow, Russia (Recruiting)

Study contacts

• Principal investigator: Elena D Belousova, Prof — Pirogov Russian National Research Medical University
• Study coordinator: Artem A Sharkov

Conditions GNAO1; Epilepsy; Hyperkinesis; hyperkinesis