A Trial of Two Fixed Doses of ZX008 (Fenfluramine HCl) as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome

Dravet Syndrome Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02826863
• Other study ID #: ZX008-1502
• Status: Recruiting
• Phase: Phase 3
• Start date: July 15, 2016
• Est. completion date: July 2020

Study information

• Verified date: January 2020
• Source: Zogenix, Inc.
• Contact: ZX008 Clinical Trials Information Desk
• Phone: 510-388-9968
• Email: ClinStudyInfo[@]zogenix.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, double-blind, parallel-group, placebo-controlled, study to assess the efficacy, safety, and pharmacokinetics of ZX008 when used as adjunctive therapy in pediatric and young adult subjects with Dravet syndrome. Subjects who qualify for the study will be randomized (1:1:1) in a double-blind manner to receive 1 of 2 doses of ZX008 or placebo. All subjects will be titrated to their randomized dose over a 14-day Titration Period. Following titration, subjects will continue treatment at their randomly assigned dose over a 12-week Maintenance Period. Total treatment time from the beginning of the Titration Period through the end of the Maintenance Period is 14 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: July 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

Key Inclusion Criteria

• Male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the Screening Visit.

• Clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs.

• Must have a minimum # of convulsive seizures per 4-week period for past 12 weeks prior to screening.

• All medications or interventions for epilepsy (including KD and VNS) must be stable for at least 4 weeks prior to screening and are expected to remain stable throughout the study.

• Parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.

Key Exclusion Criteria

• Pulmonary arterial hypertension.

• Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.

• Current or past history of glaucoma.

• Moderate or severe hepatic impairment

• Receiving concomitant therapy with: centrally-acting anorectic agents; monoamine-oxidase inhibitors; medications that act via serotonin including serotonin reuptake inhibitors; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine, and/or 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.

• Subject is unwilling to refrain from large or daily servings of grapefruits and/or Seville oranges, and their juices beginning with the Baseline Period and throughout the study.

• A clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.

• Currently receiving an investigational product.

Related Conditions & MeSH terms

• Dravet Syndrome
• Epilepsies, Myoclonic
• Spasms, Infantile
• Syndrome

Intervention

Drug:
• ZX008 - 0.8 mg/kg/day
ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 1.25 mg/mL, 2.5 mg/mL, and 5 mg/mL. The product is sugar free and is intended to be compatible with KD.
• ZX008 - 0.2 mg/kg/day
ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 1.25 mg/mL, 2.5 mg/mL, and 5 mg/mL. The product is sugar free and is intended to be compatible with KD.
• Placebo
Placebo will be administered twice a day (BID) in equally divided doses with food.

Locations

Country	Name	City	State
Australia	Melbourne Brain Centre Austin Hospital	Melbourne
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	Antwerp
Denmark	Danish National Epilepsy Centre	Dianalund
France	French Ref centre Necker Hospital Paris	Paris
Germany	Epilepsiezentrum / Neuropädiatrie Hedwig-von-Rittberg-Zentrum Für Kinder und Jugendliche	Berlin
Germany	Krankenhaus Mara Epilepsie-Zentrum Bethel	Bielefeld
Germany	Epilepsiezentrum Freiburg	Freiburg
Germany	Universitaetsklinikum Jena Klinik fuer Kinder- und Jugendmedizin Neuropaediatrie	Jena
Germany	Klinik für Neuropädiatrie Universitätsklinikum Schleswig Holstein Campus Kiel	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	Firenze
Italy	Istituto Pediatrico Giannina Gaslini Dipartimento di Neurologia	Genova
Italy	A.O Carlo Poma	Mantova
Italy	Instituto Neurologica Carlo Besta	Milano
Italy	Ospedale Fatebenefratelli e Oftalmico	Milano
Italy	U.O. Neurologia Dipartimento di Neuroscienze Ospedale Pediatrico Bambino Gesù, IRCS	Roma
Italy	Ospedal Policlinico Giambattista Rossi diBorga Roma	Verona
Japan	Okayama University Hospital	Okayama-shi	Okayama
Japan	Saitama Children's Medical Center	Saitama-shi	Saitama
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo
Japan	National Epilepsy Center Shizuoka Institute	Shizuoka-city	Shizuoka
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	Birmingham
United Kingdom	Institute of Neurosciences Queens Elizabeth University Hospital	Glasgow
United Kingdom	Alder Hey Hospital	Liverpool
United Kingdom	Evelina Hospital	London
United Kingdom	Great Ormonnd Street Hospital for Children NHS Foundation Trust	London
United Kingdom	Sheffield Children's Hospital	Sheffield

Sponsors (1)

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

Countries where clinical trial is conducted

Australia,  Belgium,  Denmark,  France,  Germany,  Italy,  Japan,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in frequency of convulsive seizures in subjects receiving ZX008 0.8mg/kg/day compared to placebo	Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity	Time between 6-week baseline assessment period and 14 week treatment and maintenance period
Secondary	Change from baseline in frequency of convulsive seizures for subjects receiving ZX008 0.2mg/kg/day compared to placebo	Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity	Time between 6-week baseline assessment period and 14 week treatment and maintenance period
Secondary	Proportion of subjects achieving a =40% or =50% reduction from baseline in convulsive seizure frequency and longest seizure-free interval in subjects receiving ZX008 0.2 and 0.8 mg/kg/day compared to placebo	Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity	Time between 6-week baseline assessment period and combined 14 week treatment and maintenance period
Secondary	Frequency and severity of seizure activity for subjects receiving ZX008 0.2mg/kg/day and 0.8mg/kg/day compared to placebo	Seizure severity evaluated using parent/caregiver seizure diary to record frequency and severity of seizure activity	Time between 6-week baseline assessment period and 14 week treatment and maintenance period
Secondary	Safety and tolerability of ZX008 0.2 and 0.8 mg/kg/day compared to placebo	Safety and tolerability will be evaluated by reported adverse events, laboratory parameters, physical and neurological examination, vital signs, electrocardiograms, echocardiograms, and body weight. (Cognitive function will be assessed using age-appropriate versions of the Brief Rating Inventory of Executive Function [BRIEF].)	Week 1 through Week 14