An Investigation to see if the investigational product ZX008 (fenfluramine hydrochloride) contributes to reducing the incidence of seizures in children and young adults with Doose syndrome, an early childhood form of epilepsy.

A proof of concept and assessment of maximal effect study with low dose Fenfluramine as add-on therapy in Myoclonic Astatic Epilepsy (Doose-Syndrome) - FFA-MAE

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-001664-38-DE

Enrollment

Registered

2019-04-02

Start date

2019-10-02

Completion date

Unknown

Last updated

2026-01-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Childhood epilepsy: Myoclonic Astatic Epilepsy (Doose-Syndrome) MedDRA version: 20.1 Level: LLT Classification code 10015040 Term: Epilepsy equivalent System Organ Class: 100000004852

Interventions

Product Name: Fenfluramine hydrochloride Pharmaceutical Form: Oral solution INN or Proposed INN: FENFLURAMINE HYDROCHLORIDE CAS Number: 404-82-0 Current Sponsor code: FFA Concentration unit: mg/ml mil

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Diagnosis of Doose syndrome • Age: 1 to 17 years. • Normal cognitive development before the onset of epilepsy and absence of organic cerebral abnormalities. • Onset of myoclonic, myoclonic-(atonic) astatic or atonic-astatic seizures, absences, status of „petit mal“, generalized tonic clonic seizures; sometimes febrile seizures occur before the start of epilepsy. • Multiple seizure types (at least 2) including in any case myoclonic atonic seizures • at least 6 documented seizures in the last 4 weeks before inclusion • on >= 1AED during the 4 weeks before inclusion • Presence on EEG of biparietal theta background rhythm, and irregularly generalized spike wave, and polyspike wave Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: • Any cardiovascular abnormality • Abnormal weight (below age specific 3rd percentile) • Cortical structural brain lesions. • Presence of severe and benign myoclonic epilepsy (SME, BME) in infancy and early childhood • Presence of cryptogenic Lennox-Gastaut syndrome, based on the ILAE definitions • Presence of atypical benign partial epilepsy/pseudo-Lennox-syndrome • Presence of other symptomatic / cryptogenic epilepsies (e.g. with a frontal lobe semiology). • Progressive neurodegenerative disease • certain drugs • Glaucoma

Design outcomes

Primary

Measure	Time frame
Main Objective: The aim of this proof of concept study is to investigate the efficacy of low dose Fenfluramine as add-on therapy 0.4 or 0.8 mg/kg/day (max 30.0 mg/day).;Secondary Objective: The aim of this proof of concept study is to investigate the quality of life and safety of low dose Fenfluramine as add-on therapy 0.4 or 0.8 mg/kg/day (max 30.0 mg/day).;Primary end point(s): Efficacy of add-on FFA in Myoclonic Astatic Epilepsy • Number of responders at each FFA dosage (0.4 or 0.8mg/kg/day) after a four week treatment with 0.4mg/kg/d or 0.8mg/kg/d (week 11/16) • Number of seizure free subjects at each FFA dosage (0.4 or 0.8mg/kg/day) after a four-week treatment with 0.4mg/kg/d or 0.8 mg/kg/day (week 11/16) • Number of seizure free days per subject during four week treatment with 0.4 mg/kg/d of FFA • Number of seizure free days per subject during four week treatment with 0.8mg/kg/d of FFA • Seizure frequency change per subject and per major seizure type: generalized tonic-clonic seizures (GTKA), tonic seizures (TS), atonic seizures (AS), absences (typical o atypical, AB), myoclonic seizures (MS) during four week treatment (0.4 mg/kg/d and 0.8 mg/kg/d) ;Timepoint(s) of evaluation of this end point: Efficacy of add-on FFA in Myoclonic Astatic Epilepsy • Number of responders at each FFA dosage: after week 11 (0.4mg/kg/d) / after week 16 (0.8mg/kg/d) • Number of seizure free subjects at each FFA dosage: after week 11 (0.4mg/kg/d) / after week 16 (0.8mg/kg/d) • Number of seizure free days per subject with 0.4mg/kg/d: during four-week treatment (week 7 - 11) • Number of seizure free days per subject with 0.8mg/kg/d during four-week treatment (week 12-16) • Seizure frequency change per subject and per major seizure type (Tonic Clonic Seizures (TCS), Tonic Seizures (TS), Atonic Seizures (AS), Focal Seizures (FS), myoclonic seizures (MS)): after week 11 (0.4mg/kg/d) / after week 16 (0.8mg/kg/d)	—

Measure

Time frame

Main Objective: The aim of this proof of concept study is to investigate the efficacy of low dose Fenfluramine as add-on therapy 0.4 or 0.8 mg/kg/day (max 30.0 mg/day).;Secondary Objective: The aim of this proof of concept study is to investigate the quality of life and safety of low dose Fenfluramine as add-on therapy 0.4 or 0.8 mg/kg/day (max 30.0 mg/day).;Primary end point(s): Efficacy of add-on FFA in Myoclonic Astatic Epilepsy • Number of responders at each FFA dosage (0.4 or 0.8mg/kg/day) after a four week treatment with 0.4mg/kg/d or 0.8mg/kg/d (week 11/16) • Number of seizure free subjects at each FFA dosage (0.4 or 0.8mg/kg/day) after a four-week treatment with 0.4mg/kg/d or 0.8 mg/kg/day (week 11/16) • Number of seizure free days per subject during four week treatment with 0.4 mg/kg/d of FFA • Number of seizure free days per subject during four week treatment with 0.8mg/kg/d of FFA • Seizure frequency change per subject and per major seizure type: generalized tonic-clonic seizures (GTKA), tonic seizures (TS), atonic seizures (AS), absences (typical o atypical, AB), myoclonic seizures (MS) during four week treatment (0.4 mg/kg/d and 0.8 mg/kg/d) ;Timepoint(s) of evaluation of this end point: Efficacy of add-on FFA in Myoclonic Astatic Epilepsy • Number of responders at each FFA dosage: after week 11 (0.4mg/kg/d) / after week 16 (0.8mg/kg/d) • Number of seizure free subjects at each FFA dosage: after week 11 (0.4mg/kg/d) / after week 16 (0.8mg/kg/d) • Number of seizure free days per subject with 0.4mg/kg/d: during four-week treatment (week 7 - 11) • Number of seizure free days per subject with 0.8mg/kg/d during four-week treatment (week 12-16) • Seizure frequency change per subject and per major seizure type (Tonic Clonic Seizures (TCS), Tonic Seizures (TS), Atonic Seizures (AS), Focal Seizures (FS), myoclonic seizures (MS)): after week 11 (0.4mg/kg/d) / after week 16 (0.8mg/kg/d)

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Secondary

Measure	Time frame
Secondary end point(s): 1) Quality of Life of add-on FFA in Myoclonic Astatic Epilepsy • CGI (clinical global impression) by caregiver and treating physician • Sleep quality (e.g. documentation with Karolinska daytime sleep scale) • Parent / caregiver 5-point scale questionnaire to assess the subjects´ development regarding cognition, motor, behavior, activity level 2) Safety of add-on FFA in Myoclonic Astatic Epilepsy • Adverse events • Laboratory safety • Vital signs • Physical examination • Neurological examination • 12-lead electrocardiogram (ECGs) • Doppler echocardiogram (ECHOs) • Body weight;Timepoint(s) of evaluation of this end point: 1) Quality of Life of add-on FFA in Myoclonic Astatic Epilepsy • CGI and 5-point developement questionnaire: baseline, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d), month 3 and 6 (in case of cardiac symptoms) • Sleep quality: baseline, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d) 2) Safety of add-on FFA in Myoclonic Astatic Epilepsy • Adverse events: continous • Laboratory safety: baseline, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d) • Vital signs:baseline, week 4, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d) •ECG/Echo: baseline, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d), month 3 and 6 (in case of cardiac symptoms)	—

Measure

Time frame

Secondary end point(s): 1) Quality of Life of add-on FFA in Myoclonic Astatic Epilepsy • CGI (clinical global impression) by caregiver and treating physician • Sleep quality (e.g. documentation with Karolinska daytime sleep scale) • Parent / caregiver 5-point scale questionnaire to assess the subjects´ development regarding cognition, motor, behavior, activity level 2) Safety of add-on FFA in Myoclonic Astatic Epilepsy • Adverse events • Laboratory safety • Vital signs • Physical examination • Neurological examination • 12-lead electrocardiogram (ECGs) • Doppler echocardiogram (ECHOs) • Body weight;Timepoint(s) of evaluation of this end point: 1) Quality of Life of add-on FFA in Myoclonic Astatic Epilepsy • CGI and 5-point developement questionnaire: baseline, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d), month 3 and 6 (in case of cardiac symptoms) • Sleep quality: baseline, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d) 2) Safety of add-on FFA in Myoclonic Astatic Epilepsy • Adverse events: continous • Laboratory safety: baseline, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d) • Vital signs:baseline, week 4, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d) •ECG/Echo: baseline, week 11 (0.4mg/kg/d) / week 16 (0.8mg/kg/d), month 3 and 6 (in case of cardiac symptoms)

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Countries

Germany

Contacts

Public ContactDepartment of Children and adolesce

UKSH

irene.lehmann@uksh.de0049043150024140

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026