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Add-on Therapy With Low Dose Fenfluramine in Lennox Gastaut Epilepsy (FFA-LGS)

Primary Purpose

Epilepsy, Lennox Gastaut Syndrome

Status
Active
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Fenfluramine
Sponsored by
KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring refractory childhood epilepsy, Lennox Gastaut syndrome, fenfluramine, anti-epileptic treatment

Eligibility Criteria

3 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

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:

    • at least 4 documented seizures in the last 4 weeks before inclusion (minimum 4 seizures in at least 2 separate weeks) Seizure types eligible for inclusion are : generalized tonic-clonic seizures GTC , tonic seizures TS , atonic seizures AS or clearly recognizable focal seizures FS.
    • on >= 2 AEDs (including VNS) during the 4 weeks before inclusion (no changes in treatment before inclusion and during the trial)
  • 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.

Exclusion Criteria

  • 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.

Sites / Locations

  • University Hospitals UZ Leuven

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

fenfluramine

Arm Description

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Seizure frequency change per patient and per major seizure type (Tonic Clonic Seizures (TCS), Tonic Seizures (TS), Atonic Seizures (AS), Focal Seizures (FS))
Adverse events (cardiac and general)
Sleep quality : 10 point scale instrument to score sleep quality
CGI (clinical global impression) scale at last visit , by patient/caregiver and treating physician

Full Information

First Posted
January 12, 2016
Last Updated
September 21, 2023
Sponsor
KU Leuven
Collaborators
Zogenix, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02655198
Brief Title
Add-on Therapy With Low Dose Fenfluramine in Lennox Gastaut Epilepsy
Acronym
FFA-LGS
Official Title
Add-on Therapy With Low Dose Fenfluramine in Lennox Gastaut Epilepsy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2016 (Actual)
Primary Completion Date
September 2018 (Actual)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
KU Leuven
Collaborators
Zogenix, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy, Lennox Gastaut Syndrome
Keywords
refractory childhood epilepsy, Lennox Gastaut syndrome, fenfluramine, anti-epileptic treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
fenfluramine
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Fenfluramine
Intervention Description
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).
Primary Outcome Measure Information:
Title
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)
Time Frame
up to 20 weeks
Secondary Outcome Measure Information:
Title
Seizure frequency change per patient and per major seizure type (Tonic Clonic Seizures (TCS), Tonic Seizures (TS), Atonic Seizures (AS), Focal Seizures (FS))
Time Frame
20 weeks
Title
Adverse events (cardiac and general)
Time Frame
20 weeks
Title
Sleep quality : 10 point scale instrument to score sleep quality
Time Frame
20 weeks
Title
CGI (clinical global impression) scale at last visit , by patient/caregiver and treating physician
Time Frame
20 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria 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: at least 4 documented seizures in the last 4 weeks before inclusion (minimum 4 seizures in at least 2 separate weeks) Seizure types eligible for inclusion are : generalized tonic-clonic seizures GTC , tonic seizures TS , atonic seizures AS or clearly recognizable focal seizures FS. on >= 2 AEDs (including VNS) during the 4 weeks before inclusion (no changes in treatment before inclusion and during the trial) 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. Exclusion Criteria 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lieven G Lagae, MD, PhD
Organizational Affiliation
Katolieke Universiteit Leuven, University Hospitals Gasthuisberg
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium

12. IPD Sharing Statement

Citations:
PubMed Identifier
30146701
Citation
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.
Results Reference
derived

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

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