Add-on Therapy With Low Dose Fenfluramine in Lennox Gastaut Epilepsy

NCT02655198 | Unknown Phase 2 DMC

• 1 other identifier: S58545
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

In this trial, the potential anti-epileptic effect of low dose fenfluramine in Lennox Gastaut epilepsy will be studied. An exploratory dose finding add-on trial is proposed. At baseline and at the end of the study, ECG and ultrasound of the heart will be performed as part of the safety follow up.

Conditions

Epilepsy; Lennox Gastaut Syndrome

Keywords

refractory childhood epilepsy; Lennox Gastaut syndrome; fenfluramine; anti-epileptic treatment

Outcome Measures

Primary Outcomes (1)

• Efficacy of add-on FFA in Lennox Gastaut epilepsy: Number of responders and seizure free patients at each FFA dosage (0,2 or 0,4 or 0,8 mg/kg/day)

  up to 20 weeks

Secondary Outcomes (4)

• Seizure frequency change per patient and per major seizure type (Tonic Clonic Seizures (TCS), Tonic Seizures (TS), Atonic Seizures (AS), Focal Seizures (FS))

  20 weeks

• Adverse events (cardiac and general)

  20 weeks

• Sleep quality : 10 point scale instrument to score sleep quality

  20 weeks

• CGI (clinical global impression) scale at last visit , by patient/caregiver and treating physician

  20 weeks

Study Arms (1)

fenfluramine

EXPERIMENTAL

Experimental : one armed open label study : Add-on fenfluramine in refractory Lennox Gastaut patients. Starting dose 0.2mg/kg/day. In non-responders (\<50% seizure frequency decrease), dose will be uptitrated every 4 weeks from 0,2 to 0,4 and max 0,8 mg/kg/day (max 30 mg). Total duration study and max exposure to the drug 20 weeks

Drug: Fenfluramine

Interventions

Fenfluramine DRUG

study of efficacy and safety of add-on fenfluramine at different dosages in refractory Lennox Gastaut patients : 0.2 - 0.4 and 0.8 mg/kg/day (max 30 mg).

fenfluramine

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Electro-clinical epilepsy syndrome compatible with Lennox Gastaut syndrome:
• Minimum requirements (based on ILAE epilepsydiagnosis.org):
• Multiple seizure types including in any case tonic seizures
• EEG shows slow spike waves and abnormal background
• Abnormal cognitive development
• MRI compatible with Lennox Gastaut epilepsy : no progressive disease
• Drug resistant:
• Age between 3 and 18 years
• Subject is male or non-pregnant, non-lactating female. Female subjects of childbearing potential must not be pregnant or breast-feeding. Female subjects of childbearing potential must have a negative urine pregnancy test. Subjects of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control, which includes abstinence, while being treated on this study and for 90 days after the last dose of study drug.

You may not qualify if:

• Known clinical cardiovascular abnormalities (including valvular problems, shunts, pulmonary hypertension, exercise intolerance)
• Any cardiac ultrasound/ECG abnormalities at baseline
• Weight below percentile 3 for age at baseline
• Subject is receiving concomitant therapy with: centrally-acting anorectic agents; monoamine oxidase 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, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates.
• Subject is unwilling to refrain from large or daily servings of grapefruits and/or Seville oranges, and their juices beginning with the Baseline Period and throughout the study.

Sponsors & Collaborators

• KU Leuven: lead
• Zogenix, Inc.: collaborator

Study Sites (1)

University Hospitals UZ Leuven

Leuven, 3000, Belgium

Location

Related Publications (1)

• Lagae L, Schoonjans AS, Gammaitoni AR, Galer BS, Ceulemans B. A pilot, open-label study of the effectiveness and tolerability of low-dose ZX008 (fenfluramine HCl) in Lennox-Gastaut syndrome. Epilepsia. 2018 Oct;59(10):1881-1888. doi: 10.1111/epi.14540. Epub 2018 Aug 26.

  PMID: 30146701 DERIVED

MeSH Terms

Conditions

Epilepsy; Lennox Gastaut Syndrome

Interventions

Fenfluramine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Lieven G Lagae, MD, PhD

  Katolieke Universiteit Leuven, University Hospitals Gasthuisberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Paediatric Neurology

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: January 13, 2016
• Study Start: January 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: December 1, 2024
• Last Updated: September 22, 2023

Record last verified: 2023-09

Locations

BE (1)