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

NCT03355209 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ZX008-16012017-002628-26
• Study Type: interventional
• Target: 296
• Locations: 14 countries
• Sites: 72

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).

Conditions

Lennox Gastaut Syndrome

Keywords

LGS

Outcome Measures

Primary Outcomes (3)

• Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in the Combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/Day Group Compared to the Placebo Group

  Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.

  From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]

• Part 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

  An Adverse event (AE) was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of investigational product, or whether considered related to the investigational product. A TEAE in Part 2 was defined as any AE with an onset on or after the first dose in Part 2. AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2.

  From Part 2 Baseline until end of the OLE Period (up to 72 months)

• Part 2: Percentage of Participants With Serious TEAEs

  A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.

  From Part 2 Baseline until end of the OLE Period (up to 72 months)

Secondary Outcomes (42)

• Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/Day Group Compared to the Placebo Group

  From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]

• Part 1: Percentage of Participants Who Achieve a >=50% Reduction From Baseline in the Frequency of Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo

  From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]

• Part 1: Percentage of Participants Who Achieve Improvement (Minimally, Much or Very Much Improved) in the CGI-I Scale as Assessed by Principal Investigator Comparing ZX008 0.8 and 0.2 mg/kg/Day Groups Independently Versus Placebo

  At Day 99 (Visit 12)

• Part 1: Percent Change From Baseline in Frequency of All Seizures That Typically Result in Drops in T+M, Whether ESC-confirmed as Drop or Not in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo

  From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]

• Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo

  From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]

Study Arms (3)

ZX008 0.2 or 0.8 mg/kg/day

EXPERIMENTAL

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

Matching Placebo

PLACEBO COMPARATOR

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

Drug: Matching Placebo

Open-Label

EXPERIMENTAL

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

Interventions

ZX008 0.2 or 0.8 mg/kg/day DRUG

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.

Open-Label; ZX008 0.2 or 0.8 mg/kg/day

Matching Placebo DRUG

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

Also known as: Placebo Comparator

Matching Placebo

Eligibility Criteria

• Age: 2 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.: lead

Study Sites (72)

Ep0214 107

Tucson, Arizona, 85718, United States

Location

Ep0214 144

Los Angeles, California, 90095-1752, United States

Location

Ep0214 101

San Francisco, California, 94158, United States

Location

Ep0214 103

Aurora, Colorado, 80045, United States

Location

Ep0214 149

Washington D.C., District of Columbia, 20010, United States

Location

Ep0214 115

Gulf Breeze, Florida, 32561, United States

Location

Ep0214 104

Miami, Florida, 33155, United States

Location

Ep0214 141

Orlando, Florida, 32803, United States

Location

Ep0214 121

Orlando, Florida, 32819, United States

Location

Ep0214 117

Atlanta, Georgia, 30328, United States

Location

Ep0214 110

Chicago, Illinois, 60611, United States

Location

Ep0214 140

Bethesda, Maryland, 20817, United States

Location

Ep0214 112

Boston, Massachusetts, 02114, United States

Location

Ep0214 136

Grand Rapids, Michigan, 49503, United States

Location

Ep0214 147

Royal Oak, Michigan, 48073, United States

Location

Ep0214 109

Rochester, Minnesota, 55905, United States

Location

Ep0214 132

Saint Paul, Minnesota, 55102, United States

Location

Ep0214 105

Hackensack, New Jersey, 07601, United States

Location

Ep0214 118

Livingston, New Jersey, 07039, United States

Location

Ep0214 150

Hartsdale, New York, 10530, United States

Location

Ep0214 142

New York, New York, 10016, United States

Location

Ep0214 131

Cleveland, Ohio, 44106, United States

Location

Ep0214 143

Portland, Oregon, 97239, United States

Location

Ep0214 120

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Ep0214 139

York, Pennsylvania, 17403, United States

Location

Ep0214 146

Dallas, Texas, 75235, United States

Location

Ep0214 126

Fort Worth, Texas, 76104, United States

Location

Ep0214 145

San Antonio, Texas, 78207-3108, United States

Location

Ep0214 106

Salt Lake City, Utah, 84113, United States

Location

Ep0214 125

Tacoma, Washington, 98405, United States

Location

Ep0214 301

Heidelberg, Australia

Location

Ep0214 302

South Brisbane, Australia

Location

Ep0214 802

Brussels, Belgium

Location

Ep0214 803

Brussels, Belgium

Location

Ep0214 801

Edegem, Belgium

Location

Ep0214 204

Toronto, Canada

Location

Ep0214 201

Vancouver, Canada

Location

Ep0214 701

Dianalund, Denmark

Location

Ep0214 1004

Bordeaux, France

Location

Ep0214 1006

Bron, France

Location

Ep0214 1005

Lille, France

Location

Ep0214 1007

Marseille, France

Location

Ep0214 1001

Paris, France

Location

Ep0214 1002

Paris, France

Location

Ep0214 902

Bielefeld, Germany

Location

Ep0214 906

Freiburg im Breisgau, Germany

Location

Ep0214 905

Jena, Germany

Location

Ep0214 908

Kiel, Germany

Location

Ep0214 903

Radeberg, Germany

Location

Ep0214 901

Vogtareuth, Germany

Location

Ep0214 1211

Bologna, Italy

Location

Ep0214 1201

Florence, Italy

Location

Ep0214 1204

Genova, Italy

Location

Ep0214 1206

Roma, Italy

Location

Ep0214 1208

Roma, Italy

Location

Ep0214 1510

Fukuoka, Japan

Location

Ep0214 1505

Niigata, Japan

Location

Ep0214 1501

Okayama, Japan

Location

Ep0214 1507

Osaka, Japan

Location

Ep0214 1504

Ōmura, Japan

Location

Ep0214 1508

Sapporo, Japan

Location

Ep0214 1506

Shinjuku-ku, Japan

Location

Ep0214 1502

Shizuoka, Japan

Location

Ep0214 1604

Guadalajara, Mexico

Location

Ep0214 1401

Zwolle, Netherlands

Location

Ep0214 1702

Bydgoszcz, Poland

Location

Ep0214 1701

Krakow, Poland

Location

Ep0214 1105

Barcelona, Spain

Location

Ep0214 1107

Barcelona, Spain

Location

Ep0214 1101

Mirasierra, Spain

Location

Ep0214 1102

Pamplona, Spain

Location

Ep0214 502

Gothenburg, Sweden

Location

Related Publications (1)

• 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.

  PMID: 35499850 DERIVED

MeSH Terms

Conditions

Lennox Gastaut Syndrome

Condition Hierarchy (Ancestors)

Epileptic Syndromes; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

001 844 599 2273

Study Officials

• UCB Cares

  001 844 599 2273

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1: Double-Blind Part 2: Open-Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1: Double-Blind ZX008 - (0.2 mg/kg/day or 0.8mg/kg/day) or Placebo and Part 2: Open-Label

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: November 28, 2017
• Study Start: November 27, 2017
• Primary Completion: May 23, 2024
• Study Completion: May 23, 2024
• Last Updated: July 3, 2025
• Results First Posted: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

PL (2); AU (2); DE (6); DK (1); SE (1); FR (6); NL (1); ME (1); CA (2); JP (8); US (30); ES (4); IT (5); BE (3)