Clinical trial NCT02823145: An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride HCl) Oral Solution in Children and Young Adults With Dravet Syndrome
Official title: An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride HCl) Oral Solution as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dravet Syndrome
Keywords: seizure
tonic clonic
epilepsy
myoclonic
encephalopathy
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2016-07-06
Enrollment: 375
Sex: ALL
Minimum age (years): 2
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Open-label Extension (OLE) Treatment Period
timeFrame: From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the OLE Treatment Period
timeFrame: From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)
measure: Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) During the OLE Treatment Period
timeFrame: From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)
Secondary outcomes:
measure: 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
timeFrame: From Day 1 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)
measure: Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Month 2 to EOS (Month 42) in the OLE Treatment Period
timeFrame: From Month 2 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)
measure: Convulsive Seizure Frequency (CSF) Per 28 Days During the OLE Treatment Period (to Month 36)
timeFrame: 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
measure: Convulsive Seizure Frequency (CSF) by Mean Daily Dose During the Overall OLE Treatment Period
timeFrame: From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)
measure: Percentage of Participants With Changes in Antiepileptic Drug (AED) Medications During First 6 Months of OLE Treatment Period
timeFrame: At Month 1, 2, 3, 4 , 5, and 6 of OLE Treatment Period
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Tucson
country: United States
facility: Center for Neurosciences - Tucson
state: Arizona
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: The Children's Hospital Colorado
state: Colorado
city: Gulf Breeze
country: United States
facility: NW FL Clinical Research Group, LLC
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital Brain Institute
state: Florida
city: Orlando
country: United States
facility: Neurology and Epilepsy Research Center
state: Florida
city: Atlanta
country: United States
facility: Clinical Integrative Research Center of Atlanta, Panda Neurology
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital Of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group, P.A.
state: Minnesota
city: Livingston
country: United States
facility: Institute of Neurology and Neurosurgery at St. Barnabus
state: New Jersey
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation
state: Washington
city: Heidelberg
country: Australia
facility: Melbourne Brain Centre Austin Hospital
city: South Brisbane
country: Australia
facility: Children's Health Queensland Hospital and Health Service at Lady Cilento Children's Hospital
city: Westmead
country: Australia
facility: The Children's Hospital Westmead Dept. of Neurology and Neurosurgery
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Montréal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
city: Dianalund
country: Denmark
facility: Danish National Epilepsy Centre
city: Amiens
country: France
facility: CHU Amiens-Picardie Service De Neurologie Pediatrique
city: Bordeaux
country: France
facility: CHU De Bordeaux Service De Pédiatrie Médicale
city: Lille
country: France
facility: CHRU Lille Antenne Pédiatrique Du CIC - Hôpital Jeanne De Flandre
city: Marseille
country: France
facility: HOPITAL DEL LA TIMONE - HOPITAL HENRI GASTAUT Hôpital De La Timone Neurologie Pédiatrique Pneumologie Pédiatrique Et Médecine Infantile
city: Paris
country: France
facility: Hôpital Robert Debré Pôle: Pédiatrie Médicale Service: Neurologie Et Maladies Métaboliques
city: Paris
country: France
facility: Hôpital Universitaire Necker-Enfants Malades Service de neurologie pédiatrique Centre de référence épilepsies rares (CReER)
city: Berlin
country: Germany
facility: DRK Kliniken Berlin - Westend Epilepsiezentrum / Neuropaediatrie
city: Bielefeld
country: Germany
facility: Krankenhaus Mara Epilepsie-Zentrum Bethel
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg Zentrum fuer Kinder- und Jugendmedizin
city: Jena
country: Germany
facility: Universitaetsklinikum Jena Klinik fuer Kinder- und Jugendmedizin Neuropaediatrie
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein Campus Kiel Klinik fuer Neuropaediatrie
city: Radeberg
country: Germany
facility: Kleinwachau Saechsisches Epilepsiezentrum Radeberg gemeinnuetzige GmbH
city: Tübingen
country: Germany
facility: Universitaetsklinik fuer Kinder- und Jugendmedizin Abteilung III
city: Vogtareuth
country: Germany
facility: Schoen Klinik Vogtareuth Neuropaediatrie und Neurologische Rehabilitation, Epilepsiezentrum fuer Kinder und Jugendlische, Tagesklinik fuer Neuropaediatrie
city: Firenze
country: Italy
facility: AOU Anna Meyer Clinica di Neurologia Pediatrica
city: Genova
country: Italy
facility: Istituto Pediatrico Giannina Gaslini Dipartimento di Neurologia
city: Mantova
country: Italy
facility: A.O. Carlo Poma
city: Milano
country: Italy
facility: Istituto Neurologica Carlo Besta
city: Milano
country: Italy
facility: Ospedale Fatebenefratelli e Oftalmico
city: Roma
country: Italy
facility: Policlinico A. Gemelli
city: Roma
country: Italy
facility: U.O. Neurologia Dipartimento di Neuroscienze Ospedale Pediatrico Bambino Gesù
city: Verona
country: Italy
facility: Ospedale Civile Maggiore di Borgo Trento - Ospedale della Donna e del Bambino
city: Saitama
country: Japan
facility: Saitama Children's Medical Center
city: Shizuoka
country: Japan
facility: National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Heeze
country: Netherlands
facility: Kempenhaeghe
city: Zwolle
country: Netherlands
facility: Stichting Epilepsie Instellingen Nederland
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Madrid
country: Spain
facility: Hospital Ruber Internacional Primera Planta Servicio de Neurologia
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra Fase 4. Segunda planta, Consulta de Pediatria
city: Birmingham
country: United Kingdom
facility: Birmingham Children Hospital NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: Institute of Neurosciences Queen Elizabeth University Hospital
city: Liverpool
country: United Kingdom
facility: Alder Hey Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
city: London
country: United Kingdom
facility: St. Thomas Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
affiliation: 001 844 599 2273
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: Cross JH, Galer BS, Gil-Nagel A, Devinsky O, Ceulemans B, Lagae L, Schoonjans AS, Donner E, Wirrell E, Kothare S, Agarwal A, Lock M, Gammaitoni AR. Impact of fenfluramine on the expected SUDEP mortality rates in patients with Dravet syndrome. Seizure. 2021 Dec;93:154-159. doi: 10.1016/j.seizure.2021.10.024. Epub 2021 Nov 2.