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: Active, not recruiting
• First Posted: November 28, 2017
• Last Update Posted: June 18, 2021
• 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)
• Actual Enrollment: 296 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: March 2024
• Estimated Study Completion Date: March 2024

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.	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
Experimental: 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

Locations

United States, Arizona

Center for Neurosciences

Tucson, Arizona, United States, 85718

United States, California

University of California Los Angeles

Los Angeles, California, United States, 90095

University of California San Francisco

San Francisco, California, United States, 94143

United States, Colorado

The Children's Hospital Colorado

Aurora, Colorado, United States, 80045

United States, District of Columbia

Childrens National Medical Center

Washington, District of Columbia, United States, 20010

United States, Florida

NW FL Clinical Research Group, LLC

Gulf Breeze, Florida, United States, 32561

Nicklaus Children's Hospital

Miami, Florida, United States, 33155

Florida Hospital Orlando

Orlando, Florida, United States, 32803

Pediatric Neurology, PA

Orlando, Florida, United States, 32819

United States, Georgia

Clinical Integrative Research Center of Atlanta, Panda Neurology

Atlanta, Georgia, United States, 30328

United States, Illinois

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, United States, 80045

United States, Maryland

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States, 20817

United States, Massachusetts

Massachusetts General Hospital For Children

Boston, Massachusetts, United States, 02114

United States, Michigan

Spectrum Health

Grand Rapids, Michigan, United States, 49503

William Beaumont Hospital

Royal Oak, Michigan, United States, 48073

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Minnesota Epilepsy Group, PA

Saint Paul, Minnesota, United States, 55102

United States, New Jersey

Northeast Regional Epilepsy Group

Hackensack, New Jersey, United States, 07601

Institute of Neurology and Neurosurgery at St. Barnabas

Livingston, New Jersey, United States, 07039

United States, New York

Icahn School of Medicine at Mount Sinai

Hartsdale, New York, United States, 10530

NYU Comprehensive Epilepsy Center

New York, New York, United States, 10016

United States, Ohio

University Hospital Cleveland

Cleveland, Ohio, United States, 44106

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Wellspan Pediatric Neurology

Manchester, Pennsylvania, United States, 17345

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104-4318

United States, Texas

UT Southwestern Medical Center

Dallas, Texas, United States, 75235

Cook Children's Medical Center

Fort Worth, Texas, United States, 76104

Baylor College of Medicine

San Antonio, Texas, United States, 78207

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84108

United States, Washington

MultiCare Institute for Research & Innovation

Tacoma, Washington, United States, 98405

Australia

Melbourne Brain Centre Austin Hospital

Heidelberg, Australia, 3084

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

South Brisbane, Australia, QLD 4101

Belgium

Hôpital Universitaire Des Enfants Reine Fabiola

Brussels, Belgium, 1020

Universitair Ziekenhuis Brussel

Brussels, Belgium, 1090

Universitair Ziekenhuis Antwerpen

Edegem, Belgium, 2650

Canada, British Columbia

British Columbia Children's Hospital

Vancouver, British Columbia, Canada, 6H 3N1

Canada, Ontario

Sick Kids

Toronto, Ontario, Canada, M5G1X8

Denmark

Epilepsihospitalet Filadelfia

Dianalund, Denmark, DK4293

France

Hôpital des enfants- Pellegrin- CIC Pédiatrique

Bordeaux, France, 33076

Hôpital Femme Mère Enfant

Bron, France, 69677

CHRU de Lille Hopital Roger Salengro Neurophysiologie Clinique (RDC)

Lille, France, 59037

AP-HM - CHU TIMONE ENFANTS Service de Neurologie Pédiatrique

Marseille, France, 13385

Hôpital de la Pitié Salpétrière

Paris, France, 75013

Hôpital Universitaire Necker-Enfants Malades Service de neurologie pédiatrique

Paris, France, 75015

Hôpital Robert Debré Pédiatrie Médicale Service Neurologie Et Maladies Métaboliques Robert-debré

Paris, France, 75019

Germany

Krankenhaus Mara GmbH

Bielefeld, Germany, 33617

Universitätsklinikum Freiburg Klinik für Neuropädiatrie und Muskelerkrankungen

Freiburg, Germany, 79016

Universitätsklinikum Jena - Klinik für Neuropädiatrie /SPZ

Jena, Germany, 07747

Universitaetsklinikum Schleswig-Holstein, Campus Kiel

Kiel, Germany, 24105

Saechsisches Epilepsiezentrum Radeberg

Radeberg, Germany, 01454

Schoen Klinik Vogtareuth - Klinik fuer Neuropediatrie und Neurologische Rehabilitation

Vogtareuth, Germany, 83569

Italy

Istituto Scienze Neurologiche di Bologna, Ospedale Bellaria

Bologna, Italy, 40123

AOU Anna Meyer Clinica di Neurologia Pediatrica

Firenze, Italy, 50139

Istituto Pediatrico Giannina Gaslini

Genova, Italy, 16147

Ospedale Pediatrico Bambino Gesù, IRCS

Roma, Italy, 00165

Policlinico Universitario A.Gemelli

Roma, Italy, 00168

Japan

Fukuoka Children's Hospital

Fukuoka-shi, Fukuoka, Japan, 813-0017

Kanagawa Children's Medical Center

Yokohama, Kanagawa, Japan, 232-8555

National Hospital Organization Nagasaki Medical Center

Omura, Nagasaki, Japan, 856-8562

National Hospital Organization Nishi-Niigata Chuo National Hospital

Niigata-shi, Niigata, Japan, 950-2085

Okayama University Hospital

Okayama-shi, Okayama, Japan, 700-8558

Osaka City General Hospital

Osaka-shi, Osaka, Japan, 534-0021

Hokkaido University Hospital

Kita-ku, Sapporo Hokkaido, Japan, 060-8648

National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka-city, Shizuoka, Japan, 420-8688

Tokyo Women's Medical University Hospital

Shinjuku-Ku, Tokyo, Japan, 162-8666

Saitama Children's Medical Center

Saitama, Japan, 330-8777

Mexico

Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde

Jalisco, Guadalajara, Mexico, 44280

Hospital Aranda de la Parra

León, Mexico, 37000

Netherlands

Epilepsy center SEIN - Zwolle

Zwolle, Netherlands, 8025BV

Poland

NZOZ Vitamed

Bydgoszcz, Poland, 85-079

Centrum Medyczne Plejady

Kraków, Poland, 30-363

Spain

Hospital Universitario Vall d'Hebron

Barcelona, Spain, 08035

Hospital del la Mar

Barcelone, Spain, 08003

Hospital Ruber Internacional Servicio de Neurologia

Madrid, Spain, 28034

Clinica Universitaria de Navarra

Pamplona, Spain, 31008

Centro de Neurologia Avanzada

Sevilla, Spain, 41013

Sweden

Sahlgrenska University Hospital

Göteborg, Sweden, 413 45

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: June 18, 2021
• Last Verified: June 2021

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