XEN1101 for Seizures

(X-ACKT Trial)

Recruiting at 148 trial locations

Overseen By Xenon Medical Affairs

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Xenon Pharmaceuticals Inc.

Must be taking: Antiseizure medications

Disqualifiers: Focal-onset seizures, Schizophrenia, Bipolar, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of the drug XEN1101 as an additional treatment for individuals with primary generalized tonic-clonic seizures, which affect the entire brain. Researchers aim to determine if XEN1101 is safe, effective, and tolerable for patients. Participants may receive either XEN1101 or a placebo, which contains no active drug. This trial may suit those who have experienced generalized seizures for over a year and have tried at least two anti-seizure medications without achieving consistent control. As a Phase 3 trial, this study is the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current anti-seizure medications throughout the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that XEN1101, the treatment under study, appears safe. Studies have found it to be well-tolerated by people with focal-onset seizures. Previous reports suggest the medication does not cause many serious side effects. It targets specific potassium channels in the brain, helping to control seizures.

Some mild side effects, such as dizziness and tiredness, have been reported, but they are usually manageable. The current trial is in Phase 3, indicating the treatment has already passed earlier safety tests. This phase primarily aims to confirm these results in a larger group of people. So far, XEN1101 seems to be a safe option for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for seizures?

Unlike the standard treatments for seizures, which often include drugs like carbamazepine or valproate, XEN1101 offers a fresh approach with its novel mechanism of action. XEN1101 is unique because it targets potassium channels to stabilize neuronal activity, potentially offering better control over seizures with fewer side effects. Researchers are excited about XEN1101 because it could provide a more targeted therapy, reducing the risk of common side effects associated with other seizure medications. Additionally, with dosing options of 15 mg/day and 25 mg/day, it offers flexibility in treatment, potentially improving patient outcomes.

What evidence suggests that XEN1101 could be an effective treatment for seizures?

Research shows that XEN1101 holds promise for treating seizures. This trial will evaluate different dosages of XEN1101—specifically 15 mg/day and 25 mg/day—alongside a placebo. XEN1101 opens certain pathways in the brain, helping to calm the overactive nerve signals that cause seizures. Studies have found that XEN1101 significantly reduces the number of seizures in people with focal-onset seizures. Additionally, long-term data suggests that many patients continue to experience fewer seizures over time, with some even becoming seizure-free. Overall, these findings support the potential effectiveness of XEN1101 in managing seizures. ^{1 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Xenon Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a BMI ≤40 who have generalized epilepsy with tonic-clonic seizures despite trying at least two anti-seizure medications. They must be on a stable dose of their current meds and able to track their seizures. Excluded are those with recent severe seizure episodes, non-epileptic psychogenic seizures, or significant mental health issues.

Inclusion Criteria

Subject is properly informed of the nature and risks of the study and gives informed consent in writing prior to entering the study (for adult subjects) and for adolescent subjects parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study

Subject is able to keep accurate seizure diaries

I have been on 1 to 3 approved seizure medications for at least a month.

Exclusion Criteria

Subject has any clinically significant laboratory abnormalities or clinically significant abnormalities on prestudy physical examination, vital signs, or ECG that, in the judgment of the investigator, indicate a medical problem that would preclude study participation, including but not limited to: a. History or presence of long QT syndrome; QTcF >450 msec at baseline; family history of sudden death of unknown cause

Any personal circumstance that, in the opinion of the investigator, prevents adherence to the protocol

Subject has history of repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

9.5 weeks

Treatment

Participants receive 12 weeks of blinded treatment with XEN1101 or placebo

12 weeks

Daily oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment with XEN1101 long-term

What Are the Treatments Tested in This Trial?

Interventions

• XEN1101

Trial Overview The study tests XEN1101 as an additional treatment for epilepsy against a placebo in a double-blind setup, meaning neither the participants nor the researchers know who's getting the real drug versus the placebo during the trial.

How Is the Trial Designed?

Group I: XEN1101 25 mg/day Experimental Treatment 1 Intervention

XEN1101 25 mg/day

Group II: XEN1101 15 mg/day Experimental Treatment 1 Intervention

XEN1101 15 mg/day

Group III: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Xenon Pharmaceuticals Inc.

Lead Sponsor

Trials

19

Recruited

3,400+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Citations

1. clinicaltrials.eu clinicaltrials.eu/inn/azetukalner/

AZETUKALNER: A Promising New Treatment for Epilepsy X-NOVA2 is a Phase 3 clinical trial designed to evaluate Azetukalner's effectiveness, safety, and tolerability in treating moderate-to-severe Major Depressive ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37812429/

Efficacy and Safety of XEN1101, a Novel Potassium ... To evaluate the efficacy and safety of XEN1101, a novel small-molecule selective Kv7.2/Kv7.3 potassium channel opener, in the treatment of focal-onset seizures ...

3. investor.xenon-pharma.com investor.xenon-pharma.com/news-releases/news-release-details/xenon-showcases-new-long-term-azetukalner-data-x-tole-ole-study

Xenon Showcases New Long-Term Azetukalner Data from X ... OLE data shows sustained monthly reduction in seizure frequency, impressive seizure freedom rates, and consistent AE safety profile suggesting long-term ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05716100

A Randomized Study of XEN1101 Versus Placebo in Focal ... Median percent change (MPC) in focal seizure frequency from baseline to DBP for XEN1101 versus placebo. From baseline through to the double blind period (week ...

5. aesnet.org aesnet.org/abstractslisting/long-term-safety-and-efficacy-of-azetukalner-a-novel-potent-kv7-potassium-channel-opener-in-adults-with-focal-epilepsy-update-from-the-ongoing-7-year-open-label-extension-of-x-tole

long-term safety and efficacy of azetukalner, a novel, potent ... Rationale: Azetukalner (XEN1101) is in development as a treatment for epilepsy and major depressive disorder. In a randomized, double-blind ...

6. trial.medpath.com trial.medpath.com/drug/report/9fc177f1b9b46acc

Azetukalner | Advanced Drug Monograph - MedPath The drug is being developed in parallel for a range of high-unmet-need neurological and psychiatric conditions, including focal onset seizures ( ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11850491/

Targeting Kv7 Potassium Channels for Epilepsy - PMC 2/3 openers, azetukalner (XEN 1101) is currently in phase III development for the treatment focal seizures, generalized tonic-clonic seizures and major ...

8. xenon-pharma.com xenon-pharma.com/wp-content/uploads/2024/04/xen1101-clinical-trial-brochure.pdf

XEN1101 Clinical Trial Brochure A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Safety and. Efficacy of XEN1101 as an Adjunctive Therapy in the Treatment of ...

9. guidetopharmacology.org guidetopharmacology.org/GRAC/LigandDisplayForward?tab=clinical&ligandId=12650

encukalner | Ligand page Comment: Encukalner (XEN1101) is a clinical stage voltage-gated potassium channel (Kv7) activator [1], that was developed as a potential anti-epileptic drug ...