Study in pediatric subjects with KCNQ2 Developmental and Epileptic Encephalopathy

Phase 1

• Conditions: KCNQ2 Developmental and Epileptic Encephalopathy; MedDRA version: 20.0Level: PTClassification code 10077380Term: Epileptic encephalopathySystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-002396-35-ES
• Lead Sponsor: Xenon Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-01
• Last Update Posted: 17 January 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Parent(s) or guardian(s) fully comprehends the nature and risks of the study and is able and willing to give informed consent in writing, prior to the subject entering the study, in accordance with local legal requirements.
2. Male or female subjects aged from 1 month (44 weeks postmenstrual age) to less than 6 years, with a body weight of =3.0 kg, at screening (Visit 1).
3. Documented evidence of a genetic test result from an appropriately accredited laboratory, consistent with a diagnosis of KCNQ2-DEE (pathogenic, likely pathogenic, variant of unknown significance, or inconclusive but unlikely to support an alternate diagnosis).
4. Seizure onset within 2 weeks after birth and EEG and documented clinical history consistent with KCNQ2-DEE.
5. Magnetic resonance imaging has been performed and is without evidence of structural abnormalities, including but not limited to, hypoxia, hypoxia-ischemia, ischemia (arterial or venous), stroke, sinovenous thrombosis, intracranial hemorrhage, or focal or global brain malformation.
6. A sufficient number of focal tonic or other countable motor seizures in the month (28 days) prior to screening, documented by caregiver report or investigator medical notes.
7. Subjects can be taking 1 and no more than the maximum required number concomitant ASMs. All doses must be stable for the required duration prior to screening and expected to be maintained throughout the duration of the study (until the end of the treatment period).
8. VNS is allowed and will not be counted as a concomitant ASM. The VNS device must be implanted for at least 6 months before before screening, and the device settings must be stable for the required duration prior to screening and throughout the duration of the study. Use of the VNS device magnet is allowed.
9. Ketogenic diet is allowed and will not be counted as a concomitant ASM. The subject must be on a stable dietary regimen that produces ketosis for the required period of time prior to screening, and expected to be maintained throughout the study.
10. In the opinion of the investigator, the caregiver is able and willing to maintain an accurate and complete daily diary to monitor seizures, diaper count (when required) and administration of study drug and concomitant medications.
Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Presence of a pathogenic or likely pathogenic variant in an additional gene associated with other epilepsy syndromes.
2. Presence of a known gain-of-function variant in the KCNQ2 gene, or clinical characteristics consistent with previously reported pathogenic gain-of-function variants in the KCNQ2 gene, such as subjects with infantile spasms without a history of neonatal-onset seizures.
3. Seizures secondary to infection, neoplasia, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive, metabolic illness, or progressive degenerative disease.
4. Confirmed diagnosis of infantile spasms within the past month prior to screening.
5. History or presence of any significant medical or surgical condition or uncontrolled medical illness at screening including, but not limited to, cardiovascular, gastrointestinal, hematologic, hepatic, ocular, pulmonary, renal, or urogenital systems, or other conditions that would not justify the subject’s participation in the study, as determined by the investigator’s risk benefit assessment.
6. QT interval corrected for heart rate by Fridericia’s formula (QTcF) of >440 msec. In addition, subjects with a history of arrhythmia, prolonged QT, heart disease or subjects taking medications known to increase the QT interval.
7. History of hyperbilirubinemia, which lasts longer than 1 week will require exclusion of hepatic disease before entering the study.
8. History of bilirubin-induced neurological dysfunction.
9. Current disturbance of micturition or known urinary obstructions or history of bladder or urinary dysfunction including abnormal post-void residual bladder ultrasound, vesicoureteral reflux, urinary retention, or required urinary catheterization in the preceding 6 months.
10. Subjects who are known to have a terminal illness.
11. Any clinically significant laboratory abnormalities or clinically significant abnormalities on pre-study physical examination, vital signs, or ECG that in the judgment of the investigator indicates a medical problem that would preclude study participation.
12. Subjects who are planned to begin to follow a ketogenic or other specialized dietary therapy during the study.
13. Caregiver history of chronic noncompliance with their child’s prescribed drug regimens that has not been corrected.
14. Exposure to any other investigational drug or device within 5 half-lives or 30 days prior to screening (Visit 1), whichever is longer or plans to participate in another drug or device trial at any time during the study.
15. Concurrent enrollment in any other type of medical research judged by the investigator not to be scientifically or medically compatible with this study.
16. Subjects using felbamate who have presented with clinically significant abnormalities and/or hepatic dysfunction during felbamate treatment, and subjects who have taken felbamate for less than 6 months prior to screening
17. Subjects who are currently taking adrenocorticotropic hormone.
18. Subjects who did not tolerate ezogabine when taken previously.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified