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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02823145
Other study ID # ZX008-1503
Secondary ID 2016-002804-14
Status Completed
Phase Phase 3
First received
Last updated
Start date June 8, 2016
Est. completion date January 27, 2023

Study information

Verified date September 2023
Source UCB Pharma
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is an international, multicenter, open-label, long-term safety study of ZX008 in subjects with Dravet syndrome.


Description:

This is an international, multicenter, open-label, long-term safety study of ZX008 in pediatric and young adult subjects with Dravet syndrome who participated in one of the core studies (ZX008-1501 and ZX008-1502) and are candidates for continuous treatment for an extended period of time. This trial will consist of a 36-month Open-Label Extension (OLE) Treatment Period and a 2-week Post-Dosing Period.


Recruitment information / eligibility

Status Completed
Enrollment 375
Est. completion date January 27, 2023
Est. primary completion date January 27, 2023
Accepts healthy volunteers No
Gender All
Age group 2 Years to 35 Years
Eligibility Key Inclusion Criteria: - Male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the core study Screening Visit. - Satisfactory completion of the core study in the opinion of the investigator and the sponsor. - Subjects who are >18 to =35 years of age at the time of screening and did not participate in one of the core studies may be eligible for participation. - A documented medical history to support a clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs. - Parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability. - Subject's parent/caregiver has been compliant with diary completion during the core study, in the opinion of the investigator (eg, at least 90% compliant). Key Exclusion Criteria: - Current or past history of cardiovascular or cerebrovascular disease, myocardial infarction or stroke. - Current cardiac valvulopathy or pulmonary hypertension that is clinically significant and warrants discontinuation of study medication. - Current or past history of glaucoma. - Moderate or severe hepatic impairment. - Receiving concomitant therapy with: centrally-acting anorectic agents; monoamineoxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates. - Currently taking carbamazepine, oxcarbamazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days, as maintenance therapy. - A clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness at Visit 1, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
ZX008 (Fenfluramine Hydrochloride)


Locations

Country Name City State
Australia Melbourne Brain Centre Austin Hospital Heidelberg
Australia Children's Health Queensland Hospital and Health Service at Lady Cilento Children's Hospital South Brisbane
Australia The Children's Hospital Westmead Dept. of Neurology and Neurosurgery Westmead
Belgium Universitair Ziekenhuis Antwerpen Edegem
Canada Centre Hospitalier Universitaire Sainte-Justine Montréal
Canada British Columbia Children's Hospital Vancouver
Denmark Danish National Epilepsy Centre Dianalund
France CHU Amiens-Picardie Service De Neurologie Pediatrique Amiens
France CHU De Bordeaux Service De Pédiatrie Médicale Bordeaux
France CHRU Lille Antenne Pédiatrique Du CIC - Hôpital Jeanne De Flandre Lille
France HOPITAL DEL LA TIMONE - HOPITAL HENRI GASTAUT Hôpital De La Timone Neurologie Pédiatrique Pneumologie Pédiatrique Et Médecine Infantile Marseille
France Hôpital Robert Debré Pôle: Pédiatrie Médicale Service: Neurologie Et Maladies Métaboliques Paris
France Hôpital Universitaire Necker-Enfants Malades Service de neurologie pédiatrique Centre de référence épilepsies rares (CReER) Paris
Germany DRK Kliniken Berlin - Westend Epilepsiezentrum / Neuropaediatrie Berlin
Germany Krankenhaus Mara Epilepsie-Zentrum Bethel Bielefeld
Germany Universitaetsklinikum Freiburg Zentrum fuer Kinder- und Jugendmedizin Freiburg
Germany Universitaetsklinikum Jena Klinik fuer Kinder- und Jugendmedizin Neuropaediatrie Jena
Germany Universitaetsklinikum Schleswig-Holstein Campus Kiel Klinik fuer Neuropaediatrie Kiel
Germany Kleinwachau Saechsisches Epilepsiezentrum Radeberg gemeinnuetzige GmbH Radeberg
Germany Universitaetsklinik fuer Kinder- und Jugendmedizin Abteilung III Tübingen
Germany Schoen Klinik Vogtareuth Neuropaediatrie und Neurologische Rehabilitation, Epilepsiezentrum fuer Kinder und Jugendlische, Tagesklinik fuer Neuropaediatrie Vogtareuth
Italy AOU Anna Meyer Clinica di Neurologia Pediatrica Firenze
Italy Istituto Pediatrico Giannina Gaslini Dipartimento di Neurologia Genova
Italy A.O. Carlo Poma Mantova
Italy Istituto Neurologica Carlo Besta Milano
Italy Ospedale Fatebenefratelli e Oftalmico Milano
Italy Policlinico A. Gemelli Roma
Italy U.O. Neurologia Dipartimento di Neuroscienze Ospedale Pediatrico Bambino Gesù Roma
Italy Ospedale Civile Maggiore di Borgo Trento - Ospedale della Donna e del Bambino Verona
Japan Saitama Children's Medical Center Saitama
Japan National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders Shizuoka
Japan Tokyo Women's Medical University Hospital Tokyo
Netherlands Kempenhaeghe Heeze
Netherlands Stichting Epilepsie Instellingen Nederland Zwolle
Spain Hospital Sant Joan de Déu Barcelona
Spain Hospital Ruber Internacional Primera Planta Servicio de Neurologia Madrid
Spain Clinica Universitaria de Navarra Fase 4. Segunda planta, Consulta de Pediatria Pamplona
United Kingdom Birmingham Children Hospital NHS Foundation Trust Birmingham
United Kingdom Institute of Neurosciences Queen Elizabeth University Hospital Glasgow
United Kingdom Alder Hey Hospital Liverpool
United Kingdom Great Ormond Street Hospital for Children NHS Foundation Trust London
United Kingdom St. Thomas Hospital London
United Kingdom Sheffield Children's Hospital Sheffield
United States Clinical Integrative Research Center of Atlanta, Panda Neurology Atlanta Georgia
United States The Children's Hospital Colorado Aurora Colorado
United States Boston Children's Hospital Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States Ann and Robert H. Lurie Children's Hospital of Chicago Chicago Illinois
United States University Hospitals Cleveland Medical Center Cleveland Ohio
United States Children's Hospital Of Michigan Detroit Michigan
United States Cook Children's Medical Center Fort Worth Texas
United States NW FL Clinical Research Group, LLC Gulf Breeze Florida
United States Institute of Neurology and Neurosurgery at St. Barnabus Livingston New Jersey
United States Le Bonheur Children's Hospital Memphis Tennessee
United States Miami Children's Hospital Brain Institute Miami Florida
United States Children's Hospital of Orange County Orange California
United States Neurology and Epilepsy Research Center Orlando Florida
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Phoenix Children's Hospital Phoenix Arizona
United States Mayo Clinic Rochester Minnesota
United States Minnesota Epilepsy Group, P.A. Saint Paul Minnesota
United States University of Utah Salt Lake City Utah
United States Rady Children's Hospital San Diego San Diego California
United States University of California San Francisco San Francisco California
United States Seattle Children's Hospital Seattle Washington
United States MultiCare Institute for Research & Innovation Tacoma Washington
United States Center for Neurosciences - Tucson Tucson Arizona

Sponsors (1)

Lead Sponsor Collaborator
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Italy,  Japan,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Open-label Extension (OLE) Treatment Period Treatment-emergent adverse events (TEAE) were defined as any AEs that based on start date information occurs after the first intake of study treatment. From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)
Primary Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the OLE Treatment Period A TEAE was defined as any AE that based on start date information occurs after the first intake of study treatment. Percentage of participants with TEAEs leading to withdrawal from IMP during OLE Treatment Period were reported. From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)
Primary Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) During the OLE Treatment Period Serious Adverse event (SAE) was defined as any untoward medical occurrence that at any dose: • results in death, • is life-threatening threatening, • results in initial inpatient hospitalization or prolongation of hospitalization, •results in persistent or significant disability or incapacity, • results in a congenital anomaly/birth defect, • results in any medically significant event that did not meet any of the other 5 SAE criteria, but which was judged by a physician to potentially jeopardize the participant or require medical or surgical intervention to prevent one of the above outcomes listed as an SAE criterion. From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)
Secondary Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Day 1 to End of Study (EOS) Visit (Month 42) in the OLE Treatment Period Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies (ZX008-1501/ZX008-1502, and ZX008-1504 Cohort 2). Participants in 1504- Cohort 1 and de novo participants (who entered 1503 without having been in any of the core studies) did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Day 1 to EOS was divided by the total number of days from Day 1 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day convulsive seizure frequency (CSF). The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant. From Day 1 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)
Secondary Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Month 2 to EOS (Month 42) in the OLE Treatment Period Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies. Participants in 1504-Cohort 1 and de novo participants did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Month 2 to EOS was divided by the total number of days from Month 2 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF. The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant. From Month 2 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)
Secondary Convulsive Seizure Frequency (CSF) Per 28 Days During the OLE Treatment Period (to Month 36) Monthly (28 day) CSF was based on electronic diary data obtained for each participant. The total number of convulsive seizures in the ith interval (CSF in OLE, where, i=1, 2, 3, … , 14 ) was divided by the total number of days in the ith interval with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF of OLE. At Month 1, Month 2, Month 3, Month 4-6, Month 7-9, Month 10-12, Month 13-15, Month 16-18, Month 19-21, Month 22-24, Month 25-27, Month 28-30, Month 31-33, and Month 34-36
Secondary Convulsive Seizure Frequency (CSF) by Mean Daily Dose During the Overall OLE Treatment Period Convulsive seizure frequency over time, reported as per 28 days was analyzed by the actual dose administered. Participants were grouped into low (0.2 to <0.4 mg/kg), medium (0.4 to <0.6 mg/kg), and high dose (>0.6 mg/kg) groups depending on their mean daily doses of ZX008 during the OLE Treatment period. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28. The convulsive seizure frequency was calculated from all available data collected. From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)
Secondary Percentage of Participants With Changes in Antiepileptic Drug (AED) Medications During First 6 Months of OLE Treatment Period Participants in the study were required to be on stable background therapy for the first 6 months of treatment, after which background AEDs could be reduced or withdrawn so long as one background AED remained. The percentage of participants who had changes in dose or type of concomitant AED medications during the first, second, third, fourth, fifth, and sixth months were analyzed and reported. At Month 1, 2, 3, 4 , 5, and 6 of OLE Treatment Period
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