An Open Label Clinical Trial to Evaluate the Efficacy and Safety of PRAX-628 in Adult Patients with Focal Onset or Primary Generalized Tonic-Clonic Seizures

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Praxis Precision Medicines Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

27 Feb 2025 → 4 Feb 2026

Decision date (initial)

2025-02-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of PRAX-628 on seizure frequency in adults with FOS or PGTCS currently taking ASMs

Secondary objectives 2

1. To evaluate the efficacy of PRAX 628 on seizure frequency in adults with FOS or PGTCS currently taking ASMs
2. To evaluate the safety and tolerability of PRAX 628 in adults with FOS or PGTCS currently taking ASMs

Conditions and MedDRA coding

Focal onset seizures or primary generalized tonic-clonic seizures

Regulatory references

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Participant and caregiver (if applicable), is willing to sign an informed consent document in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, indicating that they understand 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, including the seizure diary and contraception, and is willing to participate in the clinical trial.
2. 2. Aged ≥18 to ≤75 years of age at the time of Screening.
3. 3. A diagnosis of focal onset, seizures or idiopathic generalized tonic clonic seizures according to the International League Against Epilepsy [ILAE] Classification of Epilepsy (Fisher et al 2017).
4. 4. Prior to enrollment, evidence by computed tomography (CT) or magnetic resonance imaging (MRI) in the past that has ruled out a progressive cause of epilepsy.
5. 5. Participant must have been receiving stable doses of allowable ASMs (a minimum of 1 and a maximum of 3 ASMs). ASM treatment must be stable for at least four weeks prior to the Screening/Observation Period (Visit 1).
6. 6. Participant and/or caregiver (if applicable) self-reports at least 2 countable focal onset seizures per month for focal onset patients, or 1 countable generalized tonic-clonic seizure per month in the 3 months immediately prior to the Screening/Observation Period for PGTCS patients. (Note: Countable focal seizures are defined as 1. Focal aware seizures with observable signs; 2. Focal seizures with impaired awareness; and 3. Focal seizures to bilateral tonic-clonic seizures. 4. Primary Generalized tonic-clonic seizures)
7. 7. Participant records at least 2 countable seizures during the Screening/Observation Period for focal onset patients, or 1 countable primary generalized tonic-clonic seizure during the Screening/Observation Period for PGTCS patients.
8. 8. The participant’s seizure diary must be completed a minimum of approximately 80% of all days during the 4-week Screening/Observation Period.

Exclusion criteria 17

1. 1. History of pseudo or psychogenic seizures, or cluster seizures only, within the 12-month period preceding study entry where the individual seizures cannot be counted, or an episode of convulsive status epilepticus requiring hospitalization and intubation in the 12 months prior to Screening.
2. 2. Seizures secondary to illicit drug or alcohol use, ongoing infection, neoplasia, demyelinating disease, or central nervous system disease deemed progressive, metabolic illness, or progressive degenerative disease, progressive structural lesion or encephalopathy.
3. 3. Planned epilepsy surgery during the course of the clinical trial.
4. 4. History of neurosurgery for seizures <1 year prior to enrollment, or radiosurgery <2 years prior to enrollment.
5. 5. Schizophrenia and obsessive-compulsive disorder, or other serious mental health disorders. Uncontrolled unipolar major depression where changes in pharmacotherapy are needed or anticipated during the study.
6. 6. Active suicidal plan/intent in the past 6 months, or a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt.
7. 7. Has any significant ongoing disease, disorder, laboratory abnormalities, alcohol or drug abuse or dependence, environmental factor, or ongoing or history of any psychiatric, medical, or surgical condition that in the judgement of the investigator in consultation with the medical monitor and/or sponsor designee, might jeopardize the participant’s safety or interfere with the absorption, distribution, metabolism or excretion of PRAX-628; or impact the clinical trial objectives; or interfere with the participation in the clinical trial.
8. 8. Participants with a history of malignancy, myeloproliferative or lymphoproliferative disorders within the past 5 years are excluded. Exceptions:1) Participants with completely excised non-melanoma skin cancer (such as basal cell carcinoma or squamous cell carcinoma) or cervical carcinoma in situ are permitted at any time, 2) Participants with a history of other malignancies deemed cured by adequate treatment are also permitted at any time.
9. 16. Has any of the following: persistently abnormal test results at Screening: a serum total bilirubin value >1.5×upper limit of normal (ULN); a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >3×ULN. As an exception, participants that present with elevated bilirubin in the absence of elevations in ALT or AST that fits the pattern of Gilbert’s syndrome may be enrolled after discussion with the medical monitor and/or sponsor designee if their conjugated bilirubin is below the ULN.
10. 17. Subjects who are vulnerable including: subjects who are institutionalized, lack decisional capacity or are employees or dependent on the sponsor, investigator or trial site.”.
11. 9. History of cardiac disease(s)/cardiac conduction disorders/or cardiac structural abnormality(ies) (e.g., atrial or ventricular septal defects, valvular heart disease, coarctation of the aorta, left bundle branch block, arrhythmias, Brugada syndrome, congenital heart disease, familial short QT syndrome, presence/history of long QT syndrome or QT interval corrected with the Fridericia formula (QTcF) >450 msec, or hypertrophic obstructive cardiomyopathy) or family history of sudden death or ventricular arrhythmias, including idiopathic ventricular fibrillation (non-clinically significant patent foramen ovale (PFO) is not considered exclusionary).
12. 10. Is pregnant or breastfeeding at the time of Screening, or has a positive serum pregnancy test at Screening or is planning to become pregnant during the clinical trial or within 14 days of the last study drug dose
13. 11. Has received any other experimental or investigational drug, device or other therapy within 30 days or 5 half-lives (whichever is longer) prior to Screening, or any prior use of gene therapy.
14. 12. Vigabatrin: Use in the last 5 years without stable visual fields tested twice over the 12 months after the last dose of vigabatrin.
15. 13. Felbamate: If used as a concomitant ASM, patients must be on felbamate for at least 2 years, with a stable dose for 2 months prior to Screening. If a patient received felbamate in the past, it must have been discontinued 2 months prior to Screening.
16. 14. Participant is receiving a prohibited medications as per the prohibited concomitant medications section (Appendix 4).
17. 15. History of allergies or a severe reaction to an ASM(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Median percent change in monthly (28 days) seizure frequency from the Screening/Observation Period to the Treatment Period for PRAX-628

Secondary endpoints 9

1. Number of days after the first administration of PRAX-628 to reach the same number or higher of monthly seizures from the Screening/Observation Period to the Treatment Period
2. Impact of PRAX-628 on PGI-S and CGI-S
3. Incidence and severity of TEAEs, including discontinuation of study drug due to TEAEs
4. Changes in vital signs measurements
5. Changes in clinical laboratory results
6. Changes in ECG parameters
7. Changes in suicidality, as assessed by C-SSRS
8. Proportion of participants experiencing a ≥50% reduction in monthly (28 days) seizure frequency from the Screening/Observation Period to the Treatment Period (Responder Rate) for PRAX-628
9. Proportion of participants experiencing seizure freedom, 100% reduction in monthly (28 days) seizure frequency from the Screening/Observation Period to the Treatment Period for PRAX-628

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

Kate Sheffey

Public contact point

Organisation

Praxis Precision Medicines Inc.

Contact name

Kate Sheffey

Third parties 8

Locations

2 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 36 files

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

Application history

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