A Phase 2, Single-Blind, Placebo-Controlled Trial to Evaluate the Photoparoxysmal Electroencephalogram Response, Safety, Tolerability, and Pharmacokinetics of PRAX-628 in Participants with Epilepsy and a Photoparoxysmal Electroencephalogram Response to Intermittent Photic Stimulation

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

15 Jun 2023 → 14 Mar 2024

Decision date (initial)

2023-06-09

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, Pharmacokinetic, Pharmacodynamic, Others

To evaluate the pharmacodynamic effect of PRAX 628 compared with placebo on the IPS induced photoparoxysmal electroencephalogram response (IPS-induced PPR) in participants with epilepsy and IPS-induced PPR

Secondary objectives 2

1. To evaluate the pharmacokinetics of PRAX 628 in participants with epilepsy and IPS induced PPR
2. To evaluate the tolerability and safety of PRAX 628 compared to placebo in participants with epilepsy and IPS-induced PPR

Conditions and MedDRA coding

IPS induced photoparoxysmal electroencephalogram response (IPS-induced PPR) in participants with epilepsy and IPS-induced PPR

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Men or women between 18 and 65 years of age, inclusive.
2. Diagnosis and history of epilepsy for which they are taking 0 to 3 anti-epileptic medications
3. Epileptic patients showing a IPS-induced PPR with a standardized photosensitivity range (SPR) of at least 4 points in at least one eye condition at Screening and Baseline
4. In good health (with the exception of epilepsy) as determined at Screening and Baseline by medical history, physical examination, and laboratory evaluations
5. Has a body mass index (BMI) at Screening between 18 and 35 kg/m2 (inclusive), and a total body weight of at least 50 kg
6. Female of childbearing potential who are not pregnant or breastfeeding, have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and are not planning to get pregnant for the duration of the trial
7. Female of nonchildbearing potential by reason of surgery or at least 1 year postmenopausal (ie, 12 months since last menses) with confirmation by follicle‑stimulating hormone (FSH) at Screening only, or Female of childbearing potential who is willing to use a highly effective method or methods of contraception as defined in this protocol and for the duration prescribed in this protocol, or Male who is willing and able to use a highly effective method or methods of contraception as defined in this protocol and for the duration prescribed in this protocol
8. Able and willing to provide written informed consent and to comply with all study requirements

Exclusion criteria 22

1. A history of only non-epileptic seizures.
2. Any finding that, in the judgment of the investigator, is a clinically significant abnormality, including serum chemistry, hematology, coagulation, and urinalysis test values (abnormal test results may be repeated for confirmation).
3. An elevation of ≥2.5× upper limit of normal (ULN) for aspartate aminotransferase (AST) or alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase or ≥1.5xULN for total bilirubin.
4. Positive test for HIV, hepatitis B (HBsAg), or hepatitis C.
5. History of drug or alcohol abuse.
6. Positive drug or alcohol test at Screening or Baseline. (Abnormal test results may be repeated for confirmation.)
7. Smoker of more than 10 cigarettes per day prior to Screening or who use tobacco products equivalent to more than 10 cigarettes per day and unable to abstain from smoking while in the unit.
8. Use of an investigational drug or device within 90 days or 5 half-lives preceding the first dose of study drug, whichever is longer.
9. Use of prescription or nonprescription drugs or dietary or herbal supplements of clinical concern within 7 days or within 5 times the elimination half-life (whichever is longer) prior to the first dose of study drug. Refer to the relevant section(s) of the protocol for potential exceptions which must be approved by the sponsor/designee.
10. Any vaccination within 14 days of the first dose of study drug.
11. Other ongoing central nervous system (CNS) disease, such as an active CNS infection, demyelinating disease, degenerative neurological disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results.
12. Blood donation (including plasma donations) or significant blood loss of approximately 500 mL or more within 90 days (male) or 120 days (female) prior to first dose of study drug.
13. Presence or history of any allergy or hypersensitivity to any component of the study drug product, or history of severe allergy or anaphylaxis to a drug, food, or other exposure
14. Unwilling or unable to comply with the lifestyle considerations described in this protocol.
15. An employee or family member of an employee of the sponsor, or an employee or family member of the study site staff
16. Receiving any antiseizure drug (ASD) or non-pharmacological intervention (including ketogenic diet and vagus nerve stimulation) for the treatment of epilepsy that are NOT at stable doses, settings, or parameters for 1 month prior to Screening and are expected to make adjustments throughout the clinical trial.
17. Currently taking any sodium channel-blocking medication.
18. Any clinically significant abnormalities, medical, or psychiatric conditions identified by a detailed medical history, or physical examination, that, in the opinion of the investigator, would pose an additional safety risk to the participant or compromise the objectives of the study
19. A 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, or hypertrophic obstructive cardiomyopathy) or family history of sudden death or ventricular arrhythmias, including idiopathic ventricular fibrillation. Exception: atrioventricular block grade 1 will be allowed
20. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs or which may jeopardize the participant in case of participation in the study. Examples of such conditions include (but are not limited to): a. History of inflammatory bowel syndrome, gastritis, gastrointestinal or rectal bleeding; b. History of major gastrointestinal tract surgery (ie, gastrectomy, gastroplasty for obesity, bowel resection, etc.); c. History or evidence of pancreatic injury or pancreatitis; d. History or presence of impaired renal function as indicated by abnormal renal function (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2) or abnormal urinary constituents (eg, albuminuria).
21. Abnormal vital signs after at least 5 minutes resting in the supine position: a. Systolic blood pressure ≤90 or ≥140 mmHg; b. Diastolic blood pressure ≤40 or ≥90 mmHg; c. Heart rate ≤40 or ≥100 beats per minute; d. Body temperature ≤35.5°C or ≥37.5°C.
22. Abnormal standard 12-lead ECG after at least 5 minutes resting in the supine position: a. PR interval <120 ms with evidence of pre-excitation syndrome (e.g, delta wave) or >220 ms b. QRS >120 ms c. QTcF <350 ms or ≥450 ms if male or <360 ms or ≥460 ms if female

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Reduction or abolishment of the IPS-induced PPR

Secondary endpoints 8

1. Plasma concentrations of PRAX-628
2. Maximum observed concentration (Cmax)
3. Time to maximum observed concentration (tmax)
4. Area under the concentration-time curve from time zero to 24 hours (AUC24)
5. Incidence and severity of adverse events (AEs)
6. Changes in vital sign measurements
7. Changes in clinical laboratory results
8. Changes in electrocardiogram (ECG) parameters

Investigational products

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

Test 3

Placebo 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

02110-2320

Country

United States

Scientific contact point

Organisation

Praxis Precision Medicines Inc.

Contact name

William C. Motel

Public contact point

Organisation

Praxis Precision Medicines Inc.

Contact name

William C. Motel

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 4 files

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

Application history

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