Clinical trial NCT03355209: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lennox Gastaut Syndrome
Keywords: LGS
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2017-11-28
Enrollment: 296
Sex: ALL
Minimum age (years): 2
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Part 1: Change from baseline in frequency of seizures that result in drops in subjects receiving ZX008 compared to placebo
timeFrame: Up to 20 weeks maintenance and taper period (T+M)
Secondary outcomes:
measure: Part 2: Adverse events and related safety parameters in subjects receiving ZX008 compared to placebo
timeFrame: Up to 12 months open label
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Ep0214 107
state: Arizona
city: Los Angeles
country: United States
facility: Ep0214 144
state: California
city: San Francisco
country: United States
facility: Ep0214 101
state: California
city: Aurora
country: United States
facility: Ep0214 103
state: Colorado
city: Washington
country: United States
facility: Ep0214 149
state: District of Columbia
city: Gulf Breeze
country: United States
facility: Ep0214 115
state: Florida
city: Miami
country: United States
facility: Ep0214 104
state: Florida
city: Orlando
country: United States
facility: Ep0214 141
state: Florida
city: Orlando
country: United States
facility: Ep0214 121
state: Florida
city: Atlanta
country: United States
facility: Ep0214 117
state: Georgia
city: Chicago
country: United States
facility: Ep0214 110
state: Illinois
city: Bethesda
country: United States
facility: Ep0214 140
state: Maryland
city: Boston
country: United States
facility: Ep0214 112
state: Massachusetts
city: Grand Rapids
country: United States
facility: Ep0214 136
state: Michigan
city: Royal Oak
country: United States
facility: Ep0214 147
state: Michigan
city: Rochester
country: United States
facility: Ep0214 109
state: Minnesota
city: Saint Paul
country: United States
facility: Ep0214 132
state: Minnesota
city: Hackensack
country: United States
facility: Ep0214 105
state: New Jersey
city: Livingston
country: United States
facility: Ep0214 118
state: New Jersey
city: Hartsdale
country: United States
facility: Ep0214 150
state: New York
city: New York
country: United States
facility: Ep0214 142
state: New York
city: Cleveland
country: United States
facility: Ep0214 131
state: Ohio
city: Portland
country: United States
facility: Ep0214 143
state: Oregon
city: Philadelphia
country: United States
facility: Ep0214 120
state: Pennsylvania
city: York
country: United States
facility: Ep0214 139
state: Pennsylvania
city: Dallas
country: United States
facility: Ep0214 146
state: Texas
city: Fort Worth
country: United States
facility: Ep0214 126
state: Texas
city: San Antonio
country: United States
facility: Ep0214 145
state: Texas
city: Salt Lake City
country: United States
facility: Ep0214 106
state: Utah
city: Tacoma
country: United States
facility: Ep0214 125
state: Washington
city: Heidelberg
country: Australia
facility: Ep0214 301
city: South Brisbane
country: Australia
facility: Ep0214 302
city: Brussels
country: Belgium
facility: Ep0214 802
city: Bruxelles
country: Belgium
facility: Ep0214 803
city: Edegem
country: Belgium
facility: Ep0214 801
city: Toronto
country: Canada
facility: Ep0214 204
city: Vancouver
country: Canada
facility: Ep0214 201
city: Dianalund
country: Denmark
facility: Ep0214 701
city: Bordeaux Cedex
country: France
facility: Ep0214 1004
city: Bron
country: France
facility: Ep0214 1006
city: Lille Cedex
country: France
facility: Ep0214 1005
city: Marseilles
country: France
facility: Ep0214 1007
city: Paris
country: France
facility: Ep0214 1001
city: Paris
country: France
facility: Ep0214 1002
city: Bielefeld
country: Germany
facility: Ep0214 902
city: Freiburg
country: Germany
facility: Ep0214 906
city: Jena
country: Germany
facility: Ep0214 905
city: Kiel
country: Germany
facility: Ep0214 908
city: Radeberg
country: Germany
facility: Ep0214 903
city: Vogtareuth
country: Germany
facility: Ep0214 901
city: Bologna
country: Italy
facility: Ep0214 1211
city: Firenze
country: Italy
facility: Ep0214 1201
city: Genova
country: Italy
facility: Ep0214 1204
city: Roma
country: Italy
facility: Ep0214 1206
city: Roma
country: Italy
facility: Ep0214 1208
city: Fukuoka
country: Japan
facility: Ep0214 1510
city: Niigata-city
country: Japan
facility: Ep0214 1505
city: Okayama
country: Japan
facility: Ep0214 1501
city: Omura
country: Japan
facility: Ep0214 1504
city: Osaka
country: Japan
facility: Ep0214 1507
city: Sapporo-city
country: Japan
facility: Ep0214 1508
city: Shinjuku-ku
country: Japan
facility: Ep0214 1506
city: Shizuoka
country: Japan
facility: Ep0214 1502
city: Guadalajara
country: Mexico
facility: Ep0214 1604
city: Zwolle
country: Netherlands
facility: Ep0214 1401
city: Bydgoszcz
country: Poland
facility: Ep0214 1702
city: Krakow
country: Poland
facility: Ep0214 1701
city: Barcelona
country: Spain
facility: Ep0214 1105
city: Barcelona
country: Spain
facility: Ep0214 1107
city: Mirasierra
country: Spain
facility: Ep0214 1101
city: Pamplona
country: Spain
facility: Ep0214 1102
city: Göteborg
country: Sweden
facility: Ep0214 502
Study officials:
affiliation: 001 844 599 2273
name: UCB Cares
role: STUDY_DIRECTOR
References:
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.