A Clinical Trial to Investigate the Efficacy, Safety and Pharmacokinetics of Elsunersen in Children

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Praxis Precision Medicines Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2025-07-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Praxis Precision Medicines

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To assess the efficacy of elsunersen on seizure frequency in participants with early-onset SCN2A-DEE

Secondary objectives 6

1. Treatment Period: To assess secondary efficacy outcomes of elsunersen in participants with early-onset SCN2A-DEE
2. Treatment Period: To evaluate the safety and tolerability of elsunersen in participants with early-onset SCN2A-DEE
3. Treatment Period: To characterize the pharmacokinetics (PK) of elsunersen in participants with early-onset SCN2A-DEE
4. Extension Period: To explore long-term safety and tolerability of elsunersen in participants with early-onset SCN2A-DEE
5. Extension Period: To explore long-term efficacy outcomes of elsunersen administered to participants with early-onset SCN2A-DEE
6. Treatment & Extension Periods: To assess exploratory efficacy outcomes of elsunersen in participants with early-onset SCN2A DEE

Conditions and MedDRA coding

Voltage-gated sodium channel type II alpha subunit (SCN2A) developmental and epileptic encephalopathy (DEE)

Study design 8 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant, or parent/legal guardian, is willing to sign an informed consent document indicating that he/she understands the purpose of the clinical trial; understands, and can perform, complete, and comply with all the procedures and assessments that are required during the clinical trial; and is willing to participate in the clinical trial.
2. Has a confirmed SCN2A variant based on genetic testing.
3. Has onset of seizures prior to 3 months of age.
4. Is between the ages of 0 (with a gestational age of at least 37 weeks +1 day) to ≤18 years at Screening.
5. Seizure frequency of 4 or more countable motor seizures refractory to current treatment per 28-day during the Baseline Observation Period. Note: Countable motor seizures are defined as tonic seizures (bilateral; with or without fall or risk of fall); clonic seizures (bilateral); tonic-clonic seizures; atonic seizures (with fall or risk of fall) and atonic seizures (without fall or risk of fall); focal to bilateral tonic-clonic; focal or focal seizures with observable motor symptoms (including unilateral tonic or unilateral clonic).
6. If prescribed any ASM or non-pharmacological intervention (including ketogenic diet and vagus nerve stimulation ) for the treatment of epilepsy or other symptoms of early-onset SCN2A-DEE (auxiliary medicinal products) is on a stable dose, settings, or parameters for 1 month prior to Screening (not to include weight-based dose changes of medications).
7. Has been reviewed by the ERC prior to enrollment, including documentation of early onset SCN2A clinical phenotype , disease etiology, MRI results, and seizure frequency
8. Seizure diary completion must occur on ≥80% days in the Screening/Observation
9. Has a serum total bilirubin value <1.5× the ULN or a serum ALT or AST value <3×ULN.
10. Has an eGFR ≥ 60 mL/min/1.73 m², calculated using the Schwartz formula (updated bedside version).

Exclusion criteria 11

1. At screening, has any significant ongoing disease, disorder, laboratory abnormalities, environmental factor, or any ongoing or history of any psychiatric, medical, or surgical condition that, in the judgment of the investigator in consultation with the medical monitor and/or sponsor’s designee, might jeopardize the participant’s safety or interfere with the absorption, distribution, metabolism, or excretion of elsunersen; impact the clinical trial scientific objectives, or interfere with participation in the clinical trial.
2. Has any clinically significant or known pathogenic genetic variant other than in the SCN2A gene, or a genetic variant that may explain or contribute to the participant’s epilepsy and/or developmental disorder, in the opinion of the investigator or confirmed by the ERC.
3. Has any other/additional etiology for epilepsy and/or DEE (e.g. encephalomalacia, etc) in the opinion of the investigator or confirmed by the ERC.
4. Has bone, spine (eg, kyphosis, scoliosis), bleeding, or other disorder (including, but not limited to, intolerance to anesthesia, if applicable) that might expose the participant to risk of injury or unsuccessful lumbar puncture.
5. Is unwilling or unable to discontinue medications that might increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors) during the clinical trial (as defined in Section 6.4.1 of the protocol).
6. Is required to take any excluded medication or is anticipated to require treatment with at least 1 excluded medication during the clinical trial (as defined in the relevant section of the protocol).
7. Has laboratory test results at Screening outside the normal ranges for platelet count, prothrombin time (PT)/ partial thromboplastin time (PTT)/ international normalized ratio (INR), or renal function (serum creatinine [sCr] and urine protein [Uprot]), that are clinically meaningful as judged by the investigator.
8. Has received any experimental or investigational drug, device, or other therapy within 30 days or 5 half-lives (whichever is longer) prior to Screening, including any prior use of gene therapy. Note: This restriction does not apply to participants from PRAX 222-111 clinical trial or to patients currently receiving elsunersen through Expanded or Emergency Access, who may enroll directly into the Extension Period.
9. Has a known hypersensitivity to any component of the formulation of elsunersen.
10. Is currently pregnant or breastfeeding or is planning to become pregnant during the clinical trial or within the timeframe specified in Section 5.5.3 of the protocol.
11. Has any abnormal findings on brain MRI that may be contributing to the participant’s epilepsy, would put the participant at increased risk of ASO therapy (including but not limited to hydrocephalus), or any other finding that may be considered clinically significant as judged by the PI or ERC. Note: If a brain MRI has not been performed within 6 months of screening, the participant will need to have a brain MRI without gadolinium as part of Screening to assess ventricle size.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in monthly (28 days) motor seizure frequency from baseline to treatment after 24 weeks

Secondary endpoints 14

1. Responder rate - defined as a ≥50% reduction in monthly seizure frequency from baseline compared to treatment after 24 weeks (Treatment Period)
2. Change in motor seizure-free days from baseline (Treatment and Extension Periods)
3. Clinical Global Impression-Severity (CGI-S) at baseline compared to treatment after 24 weeks (Treatment and Extension Periods)
4. Clinical Global Impression-Improvement (CGI-I) subdomains scores at each post-dose time point (Treatment and Extension Periods)
5. Caregiver Global Impression-Severity (CgGI-S) at baseline compared to treatment after 24 weeks (Treatment and Extension Periods)
6. Caregiver Global Impression-Improvement (CgGI-I) subdomains scores at each post-dose time point (Treatment and Extension Periods)
7. Sleep assessment scores at baseline compared to each post-dose time point (Treatment and Extension Periods)
8. Incidence and severity of treatment-emergent adverse events (TEAEs) (Treatment and Extension Periods)
9. Changes in findings on physical and neurological examinations, vital sign measurements, clinical laboratory results and electrocardiogram (ECG) parameters (Treatment and Extension Periods)
10. Plasma and cerebrospinal fluid (CSF) concentrations of elsunersen (Treatment Period)
11. Plasma PK parameters of elsunersen (Treatment Period)
12. Changes in the ASM regimen, dose and number of ASMs compared to Baseline (Extension Period Only)
13. Peds QL Family Impact Module scores at baseline compared to each post-dose time point (Treatment and Extension Periods)
14. Caregiver Exit Interview (Treatment and Extension Periods)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Praxis Precision Medicines Inc.

Sponsor organisation

Praxis Precision Medicines Inc.

Address

99 High Street Floor 30th

City

Boston

Postcode

02110-2345

Country

United States

Scientific contact point

Organisation

Praxis Precision Medicines Inc.

Contact name

Scientific/public contact point

Public contact point

Organisation

Praxis Precision Medicines Inc.

Contact name

Scientific/public contact point

Third parties 1

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 61 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications