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A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy

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ClinicalTrials.gov Identifier: NCT03796962
Recruitment Status : Recruiting
First Posted : January 8, 2019
Last Update Posted : May 27, 2020
Sponsor:
Collaborator:
NCGS, Inc.
Information provided by (Responsible Party):
Xenon Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE January 2, 2019
First Posted Date  ICMJE January 8, 2019
Last Update Posted Date May 27, 2020
Actual Study Start Date  ICMJE January 30, 2019
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2020)
  • To assess the efficacy of XEN1101 compared to placebo on focal seizure frequency (e.g., median percent change in focal seizure frequency) in adults with focal epilepsy taking 1-3 antiepileptic drugs (AEDs) in the double-blind treatment period (DBP) [ Time Frame: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56) ]
    Median percent change in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo
  • To assess the safety and tolerability of XEN1101 (e.g., adverse events) in adults with focal epilepsy taking 1-3 AEDs [ Time Frame: From screening (up to 28 days prior to baseline) through to 42 days post-final dose ]
    To assess adverse events as criteria for safety and tolerability
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2019)
  • To assess the efficacy of XEN1101 compared to placebo on focal seizure frequency (e.g., median percent change in focal seizure frequency) in adults with focal epilepsy taking 1-3 antiepileptic drugs (AEDs) [ Time Frame: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56) ]
    Median percent change (MPC) in monthly (28 days) focal seizure frequency from baseline compared to double-blind treatment period versus placebo
  • To assess the safety and tolerability of XEN1101 (e.g., adverse events) in adults with focal epilepsy taking 1-3 AEDs [ Time Frame: From screening (up to 28 days prior to baseline) through to 30 days post-final dose ]
    To assess adverse events as a criteria of safety and tolerability
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2020)
  • To evaluate the 50% XEN1101 response rates in comparison to placebo in the DBP [ Time Frame: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56) ]
    Responders are defined as patients experiencing ≥50% reduction in monthly (28 days) focal seizure frequency from baseline to DBP
  • To evaluate trends in focal seizure frequency over time in the DBP [ Time Frame: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56) ]
    Percent change from baseline in weekly focal seizure frequency for each week in the DBP
Original Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2019)
  • To evaluate the 50% XEN1101 response rates in comparison to placebo [ Time Frame: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56) ]
    Responders are defined as patients experiencing ≥50% reduction in monthly (28 days) focal seizure frequency from baseline to treatment period
  • To evaluate trends in focal seizure frequency over time in the treatment period [ Time Frame: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56) ]
    Median absolute, change and percent change from baseline in weekly focal seizure frequency for each week of the double-blind treatment period
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 as Adjunctive Therapy in Focal-onset Epilepsy, With an Open-label Extension
Brief Summary The XEN1101 Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of increasing doses of XEN1101 administered as adjunctive treatment in adult patients diagnosed with focal epilepsy, followed by an optional open-label extension (OLE).
Detailed Description The XEN1101 Phase 2 clinical trial is designed as a randomized, double-blind, placebo-controlled, multicenter study with an optional open-label extension (OLE) to evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive treatment in adult patients aged 18 to 75 years diagnosed with focal epilepsy. Approximately 300 patients will be randomized in a blinded manner to one of three active treatment groups or placebo in a 2:1:1:2 fashion (XEN1101 25 mg : 20 mg : 10 mg : Placebo). After screening, patients will have 8 weeks of baseline to assess frequency of seizures, followed by 8 weeks of treatment and a 6-week post treatment follow-up period. In order to be included in the study, patients must already be treated with a stable dose of 1 to 3 allowable current anti-epileptic drugs for at least one month prior to screening, during baseline, and throughout the double-blind portion (DBP) of the study. During the treatment period, patients will be given XEN1101 or placebo once daily in the evening. A one year OLE will be available to eligible patients who complete the DBP. All patients will receive a 20 mg daily dose of XEN1101 during this extension period.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Focal Epilepsy
Intervention  ICMJE Drug: XEN1101
Oral dose
Study Arms  ICMJE
  • Experimental: 25 mg XEN1101
    Capsule filled with 25 mg XEN1101
    Intervention: Drug: XEN1101
  • Experimental: 20 mg XEN1101
    Capsule filled with 20 mg XEN1101
    Intervention: Drug: XEN1101
  • Experimental: 10 mg XEN1101
    Capsule filled with 10 mg XEN1101
    Intervention: Drug: XEN1101
  • Placebo Comparator: Placebo
    Placebo capsule
    Intervention: Drug: XEN1101
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 7, 2019)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
  • BMI ≤40 kg/m2
  • Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy [ILAE] Classification of Epilepsy (2017)
  • Prior neuroimaging within the last 10 years and documentation is available
  • Treatment with a stable dose of 1 to 3 allowable current AEDs for at least one month prior to screening, during baseline, and throughout the duration of the DBP
  • Must be willing to comply with the contraception requirements
  • Males must agree not to donate sperm from the time of the first administration of study drug until 6 months after the last dose. Females must agree not to donate ova from the time of the first administration of study drug until 6 months after the last dose.
  • Able to keep accurate seizure diaries

Key Exclusion Criteria:

  • History of pseudoseizures, psychogenic seizures, primary generalized seizure, or focal aware non-motor seizures only
  • Presence or previous history of Lennox-Gastaut syndrome
  • Seizures secondary to other diseases or conditions
  • History of repetitive seizures within the last 12 months where the individual seizures cannot be counted
  • History of neurosurgery for seizures <1 year prior to enrollment, or radiosurgery <2 years prior to enrollment
  • Schizophrenia and other psychotic disorders, or 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
  • History or presence of any significant medical or surgical condition or uncontrolled medical illness at screening, or history of cancer within the past 2 years, with the exception of appropriately treated basal cell or squamous cell carcinoma
  • Any clinically significant abnormalities on pre-study physical examination, vital signs, laboratory values or ECG indicating a medical problem that would preclude study participation including but not limited to:

    1. History of presence of long QT syndrome; QTcF > 450 msec at baseline; family history of sudden death of unknown cause
    2. History of skin or retinal pigment epithelium abnormalities caused by ezogabine
  • Past use of vigabatrin without stable visual fields tested twice over the 12 months after the last dose of vigabatrin (concomitant use of vigabatrin is not allowed)
  • If felbamate is used as a concomitant AED, patients must be taking it for at least 2 years, with a stable dose for 2 months (or no less than 49 days) and acceptable hematology and LFT history and values prior to Screening. If received in the past, felbamate must have been discontinued 2 months (or no less than 49 days) prior to Screening.
  • Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions
  • Current use of a ketogenic diet
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: NCGS, Inc. 1 844 541 4482 clinicaltrials@ncgs.com
Contact: Xenon Pharmaceuticals Inc. 1 604 484 3300 clinicaltrials@xenon-pharma.com
Listed Location Countries  ICMJE Canada,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03796962
Other Study ID Numbers  ICMJE XPF-008-201
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Xenon Pharmaceuticals Inc.
Study Sponsor  ICMJE Xenon Pharmaceuticals Inc.
Collaborators  ICMJE NCGS, Inc.
Investigators  ICMJE Not Provided
PRS Account Xenon Pharmaceuticals Inc.
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP