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

Lennox Gastaut Syndrome Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03355209
• Other study ID #: ZX008-1601
• Secondary ID: 2017-002628-26
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 27, 2017
• Est. completion date: July 1, 2024

Study information

• Verified date: April 2024
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 296
• Est. completion date: July 1, 2024
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lennox Gastaut Syndrome
• Syndrome

Intervention

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.
• Matching Placebo
Placebo will be administered twice a day (BID) in equally divided doses.

Locations

Country	Name	City	State
Australia	Ep0214 301	Heidelberg
Australia	Ep0214 302	South Brisbane
Belgium	Ep0214 802	Brussels
Belgium	Ep0214 803	Bruxelles
Belgium	Ep0214 801	Edegem
Canada	Ep0214 204	Toronto
Canada	Ep0214 201	Vancouver
Denmark	Ep0214 701	Dianalund
France	Ep0214 1004	Bordeaux Cedex
France	Ep0214 1006	Bron
France	Ep0214 1005	Lille Cedex
France	Ep0214 1007	Marseilles
France	Ep0214 1001	Paris
France	Ep0214 1002	Paris
Germany	Ep0214 902	Bielefeld
Germany	Ep0214 906	Freiburg
Germany	Ep0214 905	Jena
Germany	Ep0214 908	Kiel
Germany	Ep0214 903	Radeberg
Germany	Ep0214 901	Vogtareuth
Italy	Ep0214 1211	Bologna
Italy	Ep0214 1201	Firenze
Italy	Ep0214 1204	Genova
Italy	Ep0214 1206	Roma
Italy	Ep0214 1208	Roma
Japan	Ep0214 1510	Fukuoka
Japan	Ep0214 1505	Niigata-city
Japan	Ep0214 1501	Okayama
Japan	Ep0214 1504	Omura
Japan	Ep0214 1507	Osaka
Japan	Ep0214 1508	Sapporo-city
Japan	Ep0214 1506	Shinjuku-ku
Japan	Ep0214 1502	Shizuoka
Mexico	Ep0214 1604	Guadalajara
Netherlands	Ep0214 1401	Zwolle
Poland	Ep0214 1702	Bydgoszcz
Poland	Ep0214 1701	Krakow
Spain	Ep0214 1105	Barcelona
Spain	Ep0214 1107	Barcelona
Spain	Ep0214 1101	Mirasierra
Spain	Ep0214 1102	Pamplona
Sweden	Ep0214 502	Göteborg
United States	Ep0214 117	Atlanta	Georgia
United States	Ep0214 103	Aurora	Colorado
United States	Ep0214 140	Bethesda	Maryland
United States	Ep0214 112	Boston	Massachusetts
United States	Ep0214 110	Chicago	Illinois
United States	Ep0214 131	Cleveland	Ohio
United States	Ep0214 146	Dallas	Texas
United States	Ep0214 126	Fort Worth	Texas
United States	Ep0214 136	Grand Rapids	Michigan
United States	Ep0214 115	Gulf Breeze	Florida
United States	Ep0214 105	Hackensack	New Jersey
United States	Ep0214 150	Hartsdale	New York
United States	Ep0214 118	Livingston	New Jersey
United States	Ep0214 144	Los Angeles	California
United States	Ep0214 104	Miami	Florida
United States	Ep0214 142	New York	New York
United States	Ep0214 121	Orlando	Florida
United States	Ep0214 141	Orlando	Florida
United States	Ep0214 120	Philadelphia	Pennsylvania
United States	Ep0214 143	Portland	Oregon
United States	Ep0214 109	Rochester	Minnesota
United States	Ep0214 147	Royal Oak	Michigan
United States	Ep0214 132	Saint Paul	Minnesota
United States	Ep0214 106	Salt Lake City	Utah
United States	Ep0214 145	San Antonio	Texas
United States	Ep0214 101	San Francisco	California
United States	Ep0214 125	Tacoma	Washington
United States	Ep0214 107	Tucson	Arizona
United States	Ep0214 149	Washington	District of Columbia
United States	Ep0214 139	York	Pennsylvania

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Italy,  Japan,  Mexico,  Netherlands,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 20 weeks maintenance and taper period (T+M)
Secondary	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	Up to 12 months open label