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

Primary Purpose

Lennox Gastaut Syndrome

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ZX008 0.2 or 0.8 mg/kg/day
Matching Placebo
Sponsored by
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lennox Gastaut Syndrome focused on measuring LGS

Eligibility Criteria

2 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ep0214 107
  • Ep0214 144
  • Ep0214 101
  • Ep0214 103
  • Ep0214 149
  • Ep0214 115
  • Ep0214 104
  • Ep0214 141
  • Ep0214 121
  • Ep0214 117
  • Ep0214 110
  • Ep0214 140
  • Ep0214 112
  • Ep0214 136
  • Ep0214 147
  • Ep0214 109
  • Ep0214 132
  • Ep0214 105
  • Ep0214 118
  • Ep0214 150
  • Ep0214 142
  • Ep0214 131
  • Ep0214 143
  • Ep0214 120
  • Ep0214 139
  • Ep0214 146
  • Ep0214 126
  • Ep0214 145
  • Ep0214 106
  • Ep0214 125
  • Ep0214 301
  • Ep0214 302
  • Ep0214 802
  • Ep0214 803
  • Ep0214 801
  • Ep0214 204
  • Ep0214 201
  • Ep0214 701
  • Ep0214 1004
  • Ep0214 1006
  • Ep0214 1005
  • Ep0214 1007
  • Ep0214 1001
  • Ep0214 1002
  • Ep0214 902
  • Ep0214 906
  • Ep0214 905
  • Ep0214 908
  • Ep0214 903
  • Ep0214 901
  • Ep0214 1211
  • Ep0214 1201
  • Ep0214 1204
  • Ep0214 1206
  • Ep0214 1208
  • Ep0214 1510
  • Ep0214 1505
  • Ep0214 1501
  • Ep0214 1504
  • Ep0214 1507
  • Ep0214 1508
  • Ep0214 1506
  • Ep0214 1502
  • Ep0214 1604
  • Ep0214 1401
  • Ep0214 1702
  • Ep0214 1701
  • Ep0214 1105
  • Ep0214 1107
  • Ep0214 1101
  • Ep0214 1102
  • Ep0214 502

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

ZX008 0.2 or 0.8 mg/kg/day

Matching Placebo

Open-Label

Arm Description

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.

Part 1: Matching ZX008 placebo is supplied as an oral solution.

Part 2: ZX008 is supplied as an oral solution. Study medication will be administered twice a day (BID) in equally divided doses.

Outcomes

Primary Outcome Measures

Part 1: Change from baseline in frequency of seizures that result in drops in subjects receiving ZX008 compared to placebo
Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity

Secondary Outcome Measures

Part 2: Adverse events and related safety parameters in subjects receiving ZX008 compared to placebo
Safety and tolerability evaluated by reported adverse events, laboratory parameters, physical and neurological examination, vital signs, electrocardiograms, echocardiograms, and body weight

Full Information

First Posted
June 19, 2017
Last Updated
September 25, 2023
Sponsor
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03355209
Brief Title
A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 27, 2017 (Actual)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lennox Gastaut Syndrome
Keywords
LGS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Part 1: Double-Blind Part 2: Open-Label
Allocation
Randomized
Enrollment
296 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ZX008 0.2 or 0.8 mg/kg/day
Arm Type
Experimental
Arm Description
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.
Arm Title
Matching Placebo
Arm Type
Placebo Comparator
Arm Description
Part 1: Matching ZX008 placebo is supplied as an oral solution.
Arm Title
Open-Label
Arm Type
Experimental
Arm Description
Part 2: ZX008 is supplied as an oral solution. Study medication will be administered twice a day (BID) in equally divided doses.
Intervention Type
Drug
Intervention Name(s)
ZX008 0.2 or 0.8 mg/kg/day
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Other Intervention Name(s)
Placebo Comparator
Intervention Description
Placebo will be administered twice a day (BID) in equally divided doses.
Primary Outcome Measure Information:
Title
Part 1: Change from baseline in frequency of seizures that result in drops in subjects receiving ZX008 compared to placebo
Description
Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
Time Frame
Up to 20 weeks maintenance and taper period (T+M)
Secondary Outcome Measure Information:
Title
Part 2: Adverse events and related safety parameters in subjects receiving ZX008 compared to placebo
Description
Safety and tolerability evaluated by reported adverse events, laboratory parameters, physical and neurological examination, vital signs, electrocardiograms, echocardiograms, and body weight
Time Frame
Up to 12 months open label

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Cares
Organizational Affiliation
001 844 599 2273
Official's Role
Study Director
Facility Information:
Facility Name
Ep0214 107
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85718
Country
United States
Facility Name
Ep0214 144
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1752
Country
United States
Facility Name
Ep0214 101
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Ep0214 103
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Ep0214 149
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Ep0214 115
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
Ep0214 104
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Ep0214 141
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Ep0214 121
City
Orlando
State/Province
Florida
ZIP/Postal Code
32819
Country
United States
Facility Name
Ep0214 117
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30328
Country
United States
Facility Name
Ep0214 110
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Ep0214 140
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Ep0214 112
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Ep0214 136
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Ep0214 147
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Ep0214 109
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Ep0214 132
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Ep0214 105
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Ep0214 118
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
Facility Name
Ep0214 150
City
Hartsdale
State/Province
New York
ZIP/Postal Code
10530
Country
United States
Facility Name
Ep0214 142
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Ep0214 131
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Ep0214 143
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Ep0214 120
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104-4318
Country
United States
Facility Name
Ep0214 139
City
York
State/Province
Pennsylvania
ZIP/Postal Code
17403
Country
United States
Facility Name
Ep0214 146
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Ep0214 126
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Ep0214 145
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78207-3108
Country
United States
Facility Name
Ep0214 106
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Ep0214 125
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Ep0214 301
City
Heidelberg
Country
Australia
Facility Name
Ep0214 302
City
South Brisbane
Country
Australia
Facility Name
Ep0214 802
City
Brussels
Country
Belgium
Facility Name
Ep0214 803
City
Bruxelles
Country
Belgium
Facility Name
Ep0214 801
City
Edegem
Country
Belgium
Facility Name
Ep0214 204
City
Toronto
Country
Canada
Facility Name
Ep0214 201
City
Vancouver
Country
Canada
Facility Name
Ep0214 701
City
Dianalund
Country
Denmark
Facility Name
Ep0214 1004
City
Bordeaux Cedex
Country
France
Facility Name
Ep0214 1006
City
Bron
Country
France
Facility Name
Ep0214 1005
City
Lille Cedex
Country
France
Facility Name
Ep0214 1007
City
Marseilles
Country
France
Facility Name
Ep0214 1001
City
Paris
Country
France
Facility Name
Ep0214 1002
City
Paris
Country
France
Facility Name
Ep0214 902
City
Bielefeld
Country
Germany
Facility Name
Ep0214 906
City
Freiburg
Country
Germany
Facility Name
Ep0214 905
City
Jena
Country
Germany
Facility Name
Ep0214 908
City
Kiel
Country
Germany
Facility Name
Ep0214 903
City
Radeberg
Country
Germany
Facility Name
Ep0214 901
City
Vogtareuth
Country
Germany
Facility Name
Ep0214 1211
City
Bologna
Country
Italy
Facility Name
Ep0214 1201
City
Firenze
Country
Italy
Facility Name
Ep0214 1204
City
Genova
Country
Italy
Facility Name
Ep0214 1206
City
Roma
Country
Italy
Facility Name
Ep0214 1208
City
Roma
Country
Italy
Facility Name
Ep0214 1510
City
Fukuoka
Country
Japan
Facility Name
Ep0214 1505
City
Niigata-city
Country
Japan
Facility Name
Ep0214 1501
City
Okayama
Country
Japan
Facility Name
Ep0214 1504
City
Omura
Country
Japan
Facility Name
Ep0214 1507
City
Osaka
Country
Japan
Facility Name
Ep0214 1508
City
Sapporo-city
Country
Japan
Facility Name
Ep0214 1506
City
Shinjuku-ku
Country
Japan
Facility Name
Ep0214 1502
City
Shizuoka
Country
Japan
Facility Name
Ep0214 1604
City
Guadalajara
Country
Mexico
Facility Name
Ep0214 1401
City
Zwolle
Country
Netherlands
Facility Name
Ep0214 1702
City
Bydgoszcz
Country
Poland
Facility Name
Ep0214 1701
City
Krakow
Country
Poland
Facility Name
Ep0214 1105
City
Barcelona
Country
Spain
Facility Name
Ep0214 1107
City
Barcelona
Country
Spain
Facility Name
Ep0214 1101
City
Mirasierra
Country
Spain
Facility Name
Ep0214 1102
City
Pamplona
Country
Spain
Facility Name
Ep0214 502
City
Göteborg
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, 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. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://www.Vivli.org
Citations:
PubMed Identifier
35499850
Citation
Knupp KG, Scheffer IE, Ceulemans B, Sullivan JE, Nickels KC, Lagae L, Guerrini R, Zuberi SM, Nabbout R, Riney K, Shore S, Agarwal A, Lock M, Farfel GM, Galer BS, Gammaitoni AR, Davis R, Gil-Nagel A. Efficacy and Safety of Fenfluramine for the Treatment of Seizures Associated With Lennox-Gastaut Syndrome: A Randomized Clinical Trial. JAMA Neurol. 2022 Jun 1;79(6):554-564. doi: 10.1001/jamaneurol.2022.0829.
Results Reference
derived

Learn more about this trial

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

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