A Phase 1/2 interventional study of Antisense oligonucleotide treatment (ASO) in GNAO1, Epilepsy and Hyperkinesis, sponsored by Pirogov Russian National Research Medical University. Recruiting at 1 site in Russia. Open to participants aged 1 Year to 14 Years. Per ClinicalTrials.gov, last updated 2026-01-23.
Sponsored by Pirogov Russian National Research Medical University · Phase 1/2, Interventional, and Treatment
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:
This is an open-label study without a placebo control group due to the rare and severe nature of the disease. All participants will receive the active drug.
Participants will:
Receive escalating doses of ASO-GNAO1 via intrathecal injection over a 12-month period.
Undergo frequent neurological assessments, biomarker testing, and safety monitoring.
The variant c.607G>A in the GNAO1 gene is a gain-of-function (GOF) mutation associated with epilepsy and neurodevelopmental disorder.
ASO-GNAO1 (Tianasen) is an investigational antisense oligonucleotide (ASO) therapy designed for the treatment of GNAO1-encephalopathy. Its mechanism of action is allele-specific suppression of the mutant GNAO1 protein expression at the mRNA level. The compound mediates the degradation of mutant mRNA or inhibits its translation, thereby halting the synthesis of the pathogenic protein implicated in disease progression. This targeted suppression is anticipated to mitigate neurodegenerative processes and facilitate partial or complete restoration of neuronal function.
The drug candidate was identified through a screening platform analogous to that used for the development of Milasen, an FDA-authorized personalized ASO therapy for Batten disease. In vitro studies have demonstrated that ASO-GNAO1 (Tianasen) achieves approximately 85% suppression of the mutant GNAO1 allele activity (c.607G>A mutation) while showing no significant effect on the wild-type allele, confirming its allele-specificity.
Background and Rationale. GNAO1 encephalopathy is a severe, debilitating monogenic neurodevelopmental disorder of childhood onset, characterized by progressive motor dysfunction and drug-resistant epilepsy and hyperkinesis. Currently, there are no approved disease-modifying therapies, and management is limited to palliative and symptomatic care. The disease course is progressive, leading to severe developmental delay, profound disability, and premature mortality.
The rationale for this first-in-human study is to evaluate the potential of ASO-GNAO1 (Tianasen) to alter the natural history of the disease in a population with no alternative effective treatment options.
Study Design and Preclinical Rationale. This study constitutes the first human administration of ASO-GNAO1 (Tianasen). It is initiated as an investigational personalized therapeutic development effort for children with a rare monogenic mutation.
The preclinical toxicology program supporting this trial included single- and repeat-dose toxicity studies in rats. Doses were administered at three levels (0.2 mg/kg, 0.5 mg/kg, and 1.0 mg/kg) via intrathecal bolus injection five times over a 12-week period. The maximum observation period in the repeat-dose toxicity study was 141 days (20 weeks). The established No Observed Adverse Effect Level (NOAEL) and the overall design of the abbreviated preclinical package are consistent with the regulatory precedent set by other personalized ASOs, such as Milasen, which was authorized for a single-patient Investigational New Drug (IND) application.
Rationale for Dose Selection. The starting dose and escalation regimen for this study are based on an integrated analysis of the preclinical toxicology data, including the determination of the NOAEL and the estimated maximum tolerated dose. Further justification is derived from the known pharmacokinetic and pharmacodynamic profiles of structurally and mechanistically similar ASO compounds approved for intrathecal administration in neurological diseases, notably nusinersen and the personalized therapy milasen. Dosing is designed to remain within the established safety margins while targeting concentrations anticipated to be therapeutic based on preclinical efficacy models
1,848 studies on the registry are indexed under Epilepsy; 422 are open to participants now.
This study's planned enrollment of 5 is below the median of 50 across 1,239 interventional studies indexed under Epilepsy.
Browse Epilepsy studies →Pirogov Russian National Research Medical University is the lead sponsor of 57 studies on the registry; 15 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Treatment Resistance:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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)
Intrathecal escalating doses from 0.3 mg/kg to 1.5 mg/kg (single administration per dose level)
Also known as: Tianasen
Change in monthly seizure frequency
Change from Baseline in the number of seizure episodes per month. Unit of Measure: seizures per month
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline to Week 50
Change in epileptiform activity index on EEG
Change from Baseline in the quantitative EEG epileptiform activity index. Unit of Measure: percentage of recording time with epileptiform activity Range of Measure: 0-100%, higher value = worse
Time frame: Baseline, Week 46
Change in Barry-Albright Dystonia Scale score
Change in Barry-Albright Dystonia Scale score Unit: score (0-160), higher scores indicate worse dystonia
Time frame: Baseline, Week 46
Change in concomitant medication dosages
Change in total daily medication dose Unit: mg/kg/day
Time frame: Baseline, Week 46
Change in Gross Motor Function Measure-88 total score
Change in Gross Motor Function Measure-88 total score Unit: score (0-100), higher scores indicate better function
Time frame: Baseline, Week 46
Change in Denver Developmental Screening Test developmental age
Change in Denver Developmental Screening Test developmental age Unit: developmental age in months
Time frame: baseline and week 46
Change in Leiter-3 nonverbal IQ score
Change in Leiter-3 nonverbal IQ score. Unit: IQ score (standard score 30-170)
Time frame: Baseline and week 46
Plan to share: Yes — all IPD that underlie results in a publication are to be shared
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
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.
No publications or documents are linked to this record.
Started Sep 2025 (actual). Primary completion is estimated for Dec 2026, 15 months after the start.
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Pirogov Russian National Research Medical University