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

NCT02823145 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ZX008-15032016-002804-14
• Study Type: interventional
• Target: 375
• Locations: 12 countries
• Sites: 67

Brief Summary

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

Conditions

Dravet Syndrome

Keywords

seizure; tonic clonic; epilepsy; myoclonic; encephalopathy

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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 Outcomes (5)

• 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

  From Day 1 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)

• Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Month 2 to EOS (Month 42) in the OLE Treatment Period

  From Month 2 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)

• Convulsive Seizure Frequency (CSF) Per 28 Days During the OLE Treatment Period (to Month 36)

  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

• Convulsive Seizure Frequency (CSF) by Mean Daily Dose During the Overall OLE Treatment Period

  From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)

• Percentage of Participants With Changes in Antiepileptic Drug (AED) Medications During First 6 Months of OLE Treatment Period

  At Month 1, 2, 3, 4 , 5, and 6 of OLE Treatment Period

Study Arms (1)

ZX008

EXPERIMENTAL

ZX008 is supplied as an oral solution in a concentration of 2.5 mg/mL. Subjects will be titrated to an effective dose beginning with 0.2 mg/kg/day (maximum: 30 mg/day).

Drug: ZX008 (Fenfluramine Hydrochloride)

Interventions

ZX008 (Fenfluramine Hydrochloride) DRUG

ZX008

Eligibility Criteria

• Age: 2 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.: lead

Study Sites (67)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Center for Neurosciences - Tucson

Tucson, Arizona, 85718, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

The Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

NW FL Clinical Research Group, LLC

Gulf Breeze, Florida, 32561, United States

Location

Miami Children's Hospital Brain Institute

Miami, Florida, 33155, United States

Location

Neurology and Epilepsy Research Center

Orlando, Florida, 32819, United States

Location

Clinical Integrative Research Center of Atlanta, Panda Neurology

Atlanta, Georgia, 30328, United States

Location

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital Of Michigan

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Minnesota Epilepsy Group, P.A.

Saint Paul, Minnesota, 55102, United States

Location

Institute of Neurology and Neurosurgery at St. Barnabus

Livingston, New Jersey, 07039, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44103, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

University of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MultiCare Institute for Research & Innovation

Tacoma, Washington, 98405, United States

Location

Melbourne Brain Centre Austin Hospital

Heidelberg, Australia

Location

Children's Health Queensland Hospital and Health Service at Lady Cilento Children's Hospital

South Brisbane, Australia

Location

The Children's Hospital Westmead Dept. of Neurology and Neurosurgery

Westmead, Australia

Location

Universitair Ziekenhuis Antwerpen

Edegem, Belgium

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Canada

Location

British Columbia Children's Hospital

Vancouver, Canada

Location

Danish National Epilepsy Centre

Dianalund, Denmark

Location

CHU Amiens-Picardie Service De Neurologie Pediatrique

Amiens, France

Location

CHU De Bordeaux Service De Pédiatrie Médicale

Bordeaux, France

Location

CHRU Lille Antenne Pédiatrique Du CIC - Hôpital Jeanne De Flandre

Lille, France

Location

HOPITAL DEL LA TIMONE - HOPITAL HENRI GASTAUT Hôpital De La Timone Neurologie Pédiatrique Pneumologie Pédiatrique Et Médecine Infantile

Marseille, France

Location

Hôpital Robert Debré Pôle: Pédiatrie Médicale Service: Neurologie Et Maladies Métaboliques

Paris, France

Location

Hôpital Universitaire Necker-Enfants Malades Service de neurologie pédiatrique Centre de référence épilepsies rares (CReER)

Paris, France

Location

DRK Kliniken Berlin - Westend Epilepsiezentrum / Neuropaediatrie

Berlin, Germany

Location

Krankenhaus Mara Epilepsie-Zentrum Bethel

Bielefeld, Germany

Location

Universitaetsklinikum Freiburg Zentrum fuer Kinder- und Jugendmedizin

Freiburg im Breisgau, Germany

Location

Universitaetsklinikum Jena Klinik fuer Kinder- und Jugendmedizin Neuropaediatrie

Jena, Germany

Location

Universitaetsklinikum Schleswig-Holstein Campus Kiel Klinik fuer Neuropaediatrie

Kiel, Germany

Location

Kleinwachau Saechsisches Epilepsiezentrum Radeberg gemeinnuetzige GmbH

Radeberg, Germany

Location

Universitaetsklinik fuer Kinder- und Jugendmedizin Abteilung III

Tübingen, Germany

Location

Schoen Klinik Vogtareuth Neuropaediatrie und Neurologische Rehabilitation, Epilepsiezentrum fuer Kinder und Jugendlische, Tagesklinik fuer Neuropaediatrie

Vogtareuth, Germany

Location

AOU Anna Meyer Clinica di Neurologia Pediatrica

Florence, Italy

Location

Istituto Pediatrico Giannina Gaslini Dipartimento di Neurologia

Genova, Italy

Location

A.O. Carlo Poma

Mantova, Italy

Location

Istituto Neurologica Carlo Besta

Milan, Italy

Location

Ospedale Fatebenefratelli e Oftalmico

Milan, Italy

Location

Policlinico A. Gemelli

Roma, Italy

Location

U.O. Neurologia Dipartimento di Neuroscienze Ospedale Pediatrico Bambino Gesù

Roma, Italy

Location

Ospedale Civile Maggiore di Borgo Trento - Ospedale della Donna e del Bambino

Verona, Italy

Location

Saitama Children's Medical Center

Saitama, Japan

Location

National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka, Japan

Location

Tokyo Women's Medical University Hospital

Tokyo, Japan

Location

Kempenhaeghe

Heeze, Netherlands

Location

Stichting Epilepsie Instellingen Nederland

Zwolle, Netherlands

Location

Hospital Sant Joan de Déu

Barcelona, Spain

Location

Hospital Ruber Internacional Primera Planta Servicio de Neurologia

Madrid, Spain

Location

Clinica Universitaria de Navarra Fase 4. Segunda planta, Consulta de Pediatria

Pamplona, Spain

Location

Birmingham Children Hospital NHS Foundation Trust

Birmingham, United Kingdom

Location

Institute of Neurosciences Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

Alder Hey Hospital

Liverpool, United Kingdom

Location

Great Ormond Street Hospital for Children NHS Foundation Trust

London, United Kingdom

Location

St. Thomas Hospital

London, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, United Kingdom

Location

Related Publications (2)

• Scheffer IE, Nabbout R, Lagae L, Devinsky O, Auvin S, Thiele EA, Wirrell EC, Polster T, Specchio N, Pringsheim M, Imai K, Lock MD, Langlois M, Roper RZ, Lothe A, Sullivan J. Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome. Epilepsia. 2025 Jun;66(6):1919-1932. doi: 10.1111/epi.18342. Epub 2025 Mar 12.

  PMID: 40072476 RESULT

• 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.

  PMID: 34768178 DERIVED

MeSH Terms

Conditions

Epilepsies, Myoclonic; Seizures; Epilepsy; Brain Diseases

Interventions

Fenfluramine

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

001 844 599 2273

Study Officials

• UCB Cares

  001 844 599 2273

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2016
• First Posted: July 6, 2016
• Study Start: June 8, 2016
• Primary Completion: January 27, 2023
• Study Completion: January 27, 2023
• Last Updated: July 14, 2025
• Results First Posted: September 25, 2023

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.

Locations

JP (3); FR (6); IT (8); US (24); GB (6); CA (2); BE (1); AU (3); DK (1); NL (2); DE (8); ES (3)