A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome

• ClinicalTrials.gov Identifier: NCT03355209
• Recruitment Status: Recruiting
• First Posted: November 28, 2017
• Last Update Posted: September 17, 2020
• Sponsor: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
• Information provided by (Responsible Party): Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )

Study Description

Brief Summary:

This is a two-part, multicenter, double-blind, parallel-group, placebo controlled study to evaluate the effect of ZX008 when used as adjunctive therapy for the treatment of uncontrolled seizures in children and adults with Lennox-Gastaut syndrome (LGS).

Condition or disease	Intervention/treatment	Phase
Lennox Gastaut Syndrome	Drug: ZX008 0.2 or 0.8 mg/kg/day; Drug: Matching Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 225 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Part 1: Double-Blind ZX008 - (0.2 mg/kg/day or 0.8mg/kg/day) or Placebo and Part 2: Open-Label
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Part 1: Double-Blind Part 2: Open-Label
• Primary Purpose: Treatment
• Official Title: A Two-Part Study of ZX008 in Children and Adults With Lennox-Gastaut Syndrome (LGS); Part 1: A Randomized, Double-blind, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as Adjunctive Therapy for Seizures in Children and Adults With LGS, Followed by Part 2: An Open-label Extension to Assess Long-Term Safety of ZX008 in Children and Adults With LGS
• Actual Study Start Date: November 27, 2017
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: ZX008 0.2 or 0.8 mg/kg/day; Part 1: ZX008 is supplied as an oral solution. Subjects will be randomized to receive 1 of 2 doses of ZX008 (0.2 mg/kg/day or 0.8 mg/kg/day) or placebo.	Drug: ZX008 0.2 or 0.8 mg/kg/day; ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride. The product is sugar free and is intended to be compatible with a Ketogenic Diet.
Placebo Comparator: Matching Placebo; Part 1: Matching ZX008 placebo is supplied as an oral solution.	Drug: Matching Placebo; Placebo will be administered twice a day (BID) in equally divided doses.; Other Name: Placebo Comparator
Placebo Comparator: Open-Label; Part 2: ZX008 is supplied as an oral solution. Study medication will be administered twice a day (BID) in equally divided doses.	Drug: ZX008 0.2 or 0.8 mg/kg/day; ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride. The product is sugar free and is intended to be compatible with a Ketogenic Diet.

Outcome Measures

Primary Outcome Measures :

1. Part 1: Change from baseline in frequency of seizures that result in drops in subjects receiving ZX008 compared to placebo [ Time Frame: Up to 20 weeks maintenance and taper period (T+M) ]
   Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity

Secondary Outcome Measures :

1. Part 2: Adverse events and related safety parameters in subjects receiving ZX008 compared to placebo [ Time Frame: Up to 12 months open label ]
   Safety and tolerability evaluated by reported adverse events, laboratory parameters, physical and neurological examination, vital signs, electrocardiograms, echocardiograms, and body weight

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 35 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Male or non-pregnant, non-lactating female, age 2 to 35 years, inclusive as of the day of the Screening Visit.
• Clinical diagnosis of Lennox-Gastaut syndrome, where seizures that result in drops are not completely controlled by current antiepileptic treatments.
• Onset of seizures at 11 years of age or younger.
• Abnormal cognitive development.
• Must be receiving at least 1 concomitant AED and up to 4 concomitant anti-epileptic treatments.

Key Exclusion Criteria:

• Etiology of seizures is a degenerative neurological disease.
• History of hemiclonic seizures in the first year of life.
• Subject only has drop seizures in clusters, where individual seizures cannot be counted reliably.
• Pulmonary arterial hypertension.
• Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.
• 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.
• Taking felbamate for less than 1 year prior to screening and/or does not have stable liver function and hematology laboratory tests, and/or the dose has not been stable for at least 60 days prior to the Screening Visit.
• Currently receiving an investigational product.
• Institutionalized in a general nursing home (ie, in a facility that does not specialize in epilepsy care).
• 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.

Contacts and Locations

Contacts

Contact: ZX008 Clinical Trials Information Desk; 510-338-9968; ClinStudyInfo@zogenix.com

Locations

United States, Arizona

Center for Neurosciences; Active, not recruiting

Tucson, Arizona, United States, 85718

United States, California

University of California Los Angeles; Active, not recruiting

Los Angeles, California, United States, 90095

University of California San Francisco; Active, not recruiting

San Francisco, California, United States, 94143

United States, Colorado

The Children's Hospital Colorado; Active, not recruiting

Aurora, Colorado, United States, 80045

United States, District of Columbia

Childrens National Medical Center; Active, not recruiting

Washington, District of Columbia, United States, 20010

United States, Florida

NW FL Clinical Research Group, LLC; Active, not recruiting

Gulf Breeze, Florida, United States, 32561

Nicklaus Children's Hospital; Active, not recruiting

Miami, Florida, United States, 33155

Florida Hospital Orlando; Active, not recruiting

Orlando, Florida, United States, 32803

Pediatric Neurology, PA; Active, not recruiting

Orlando, Florida, United States, 32819

United States, Georgia

Clinical Integrative Research Center of Atlanta, Panda Neurology; Active, not recruiting

Atlanta, Georgia, United States, 30328

United States, Illinois

Ann & Robert Lurie Children's Hospital of Chicago; Completed

Chicago, Illinois, United States, 80045

United States, Maryland

Mid-Atlantic Epilepsy and Sleep Center; Active, not recruiting

Bethesda, Maryland, United States, 20817

United States, Massachusetts

Massachusetts General Hospital For Children; Active, not recruiting

Boston, Massachusetts, United States, 02114

United States, Michigan

Spectrum Health; Completed

Grand Rapids, Michigan, United States, 49503

William Beaumont Hospital; Active, not recruiting

Royal Oak, Michigan, United States, 48073

United States, Minnesota

Mayo Clinic; Active, not recruiting

Rochester, Minnesota, United States, 55905

Minnesota Epilepsy Group, PA; Active, not recruiting

Saint Paul, Minnesota, United States, 55102

United States, New Jersey

Northeast Regional Epilepsy Group; Active, not recruiting

Hackensack, New Jersey, United States, 07601

Institute of Neurology and Neurosurgery at St. Barnabas; Active, not recruiting

Livingston, New Jersey, United States, 07039

United States, New York

Icahn School of Medicine at Mount Sinai; Active, not recruiting

Hartsdale, New York, United States, 10530

NYU Comprehensive Epilepsy Center; Active, not recruiting

New York, New York, United States, 10016

United States, Ohio

University Hospital Cleveland; Active, not recruiting

Cleveland, Ohio, United States, 44106

United States, Oregon

Oregon Health & Science University; Active, not recruiting

Portland, Oregon, United States, 97239

United States, Pennsylvania

Wellspan Pediatric Neurology; Active, not recruiting

Manchester, Pennsylvania, United States, 17345

Children's Hospital of Philadelphia; Active, not recruiting

Philadelphia, Pennsylvania, United States, 19104-4318

United States, Texas

UT Southwestern Medical Center; Active, not recruiting

Dallas, Texas, United States, 75235

Cook Children's Medical Center; Active, not recruiting

Fort Worth, Texas, United States, 76104

Baylor College of Medicine; Active, not recruiting

San Antonio, Texas, United States, 78207

United States, Utah

University of Utah; Active, not recruiting

Salt Lake City, Utah, United States, 84108

United States, Washington

MultiCare Institute for Research & Innovation; Active, not recruiting

Tacoma, Washington, United States, 98405

Australia

Melbourne Brain Centre Austin Hospital; Active, not recruiting

Heidelberg, Australia, 3084

Children's Health Queensland Hospital and Health Service at Lady Cilento Children's Hospital; Active, not recruiting

South Brisbane, Australia, QLD 4101

Belgium

Universitair Ziekenhuis Antwerpen; Active, not recruiting

Antwerpen, Belgium, 2650

Hôpital Universitaire Des Enfants Reine Fabiola; Active, not recruiting

Brussels, Belgium, 1020

Universitair Ziekenhuis Brussel; Active, not recruiting

Brussels, Belgium, 1090

Canada, British Columbia

British Columbia Children's Hospital; Active, not recruiting

Vancouver, British Columbia, Canada, 6H 3N1

Canada, Ontario

Sick Kids; Active, not recruiting

Toronto, Ontario, Canada, M5G1X8

Denmark

Epilepsihospitalet Filadelfia; Active, not recruiting

Dianalund, Denmark, DK4293

France

Hôpital des enfants- Pellegrin- CIC Pédiatrique; Active, not recruiting

Bordeaux, France, 33076

Hôpital Femme Mère Enfant; Active, not recruiting

Bron, France, 69677

CHRU de Lille Hopital Roger Salengro Neurophysiologie Clinique (RDC); Active, not recruiting

Lille, France, 59037

AP-HM - CHU TIMONE ENFANTS Service de Neurologie Pédiatrique; Active, not recruiting

Marseille, France, 13385

Hôpital Universitaire Necker-Enfants Malades Service de neurologie pédiatrique; Active, not recruiting

Paris, France, 75015

Hôpital Robert Debré Pédiatrie Médicale Service Neurologie Et Maladies Métaboliques Robert-debré; Active, not recruiting

Paris, France, 75019

Germany

Krankenhaus Mara GmbH; Active, not recruiting

Bielefeld, Germany, 33617

Universitetsklinik Freiburg; Active, not recruiting

Friedberg, Germany

Universitätsklinikum Jena - Klinik für Neuropädiatrie /SPZ; Active, not recruiting

Jena, Germany

Universitaetsklinikum Schleswig-Holstein, Campus Kiel; Active, not recruiting

Kiel, Germany

Sächsisches Epilepsie-Zentrum Radeberg; Active, not recruiting

Radeberg, Germany

Schoen Klinik Vogtareuth - Klinik fuer Neuropediatrie und Neurologische Rehabilitation; Active, not recruiting

Vogtareuth, Germany

Italy

Ospedale Bellaria; Active, not recruiting

Bologna, Italy

AOU Anna Meyer Clinica di Neurologia Pediatrica; Active, not recruiting

Firenze, Italy, 50139

Istituto Pediatrico Giannina Gaslini; Active, not recruiting

Genova, Italy, 16148

Ospedale Bambino Gesù, IRCS; Active, not recruiting

Roma, Italy, 00165

Unita Operativa di Neuropsichiatria Infantile, Universita Cattolica del Sacro Cuore, Fondazione Poli; Active, not recruiting

Roma, Italy, 00168

Japan

National Hospital Organization Nagasaki Medical Center; Recruiting

Omura, Nagasaki, Japan

National Hospital Organization Nishi-Niigata Chuo National Hospital; Recruiting

Niigata-shi, Niigata, Japan

Okayama University Hospital; Recruiting

Okayama-shi, Okayama, Japan

National Epilepsy Center Shizuoka; Recruiting

Shizuoka-city, Shizuoka, Japan

Mexico

Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde; Active, not recruiting

Jalisco, Guadalajara, Mexico, 44280

Hospital Aranda de la Parra; Active, not recruiting

Mexico, Mexico

Netherlands

Epilepsy center SEIN - Zwolle; Active, not recruiting

Zwolle, Netherlands, 8025BV

Poland

NZOZ Vitamed; Active, not recruiting

Bydgoszcz, Poland, 85-079

Centrum Medyczne Plejady; Active, not recruiting

Kraków, Poland, 30-363

Spain

Hospital del Mar; Active, not recruiting

Barcelona, Spain, 08022

Hospital Universitario Vall d'Hebron; Active, not recruiting

Barcelona, Spain

Hospital Ruber Internacional Servicio de Neurologia; Active, not recruiting

Madrid, Spain, 28034

Clinica Universitaria de Navarra; Active, not recruiting

Pamplona, Spain, 31008

Sweden

Sahlgrenska University Hospital; Active, not recruiting

Göteborg, Sweden

Sponsors and Collaborators

Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.

More Information

• Responsible Party: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
• ClinicalTrials.gov Identifier: NCT03355209
• Other Study ID Numbers: ZX008-1601
• First Posted: November 28, 2017
• Last Update Posted: September 17, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. ):

LGS

Additional relevant MeSH terms:

Lennox Gastaut Syndrome; Syndrome; Disease; Pathologic Processes; Epileptic Syndromes; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn