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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002804-14 | EudraCT Number |
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This is an international, multicenter, open-label, long-term safety study of ZX008 in subjects with Dravet syndrome.
This is an international, multicenter, open-label, long-term safety study of ZX008 in pediatric and young adult subjects with Dravet syndrome who participated in one of the core studies (ZX008-1501 and ZX008-1502) and are candidates for continuous treatment for an extended period of time. This trial will consist of a 36-month Open-Label Extension (OLE) Treatment Period and a 2-week Post-Dosing Period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ZX008 | Experimental | ZX008 is supplied as an oral solution in a concentration of 2.5 mg/mL. Subjects will be titrated to an effective dose beginning with 0.2 mg/kg/day (maximum: 30 mg/day). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZX008 (Fenfluramine Hydrochloride) | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Open-label Extension (OLE) Treatment Period | Treatment-emergent adverse events (TEAE) were defined as any AEs that based on start date information occurs after the first intake of study treatment. | From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42) |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the OLE Treatment Period | A TEAE was defined as any AE that based on start date information occurs after the first intake of study treatment. Percentage of participants with TEAEs leading to withdrawal from IMP during OLE Treatment Period were reported. | From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42) |
| Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) During the OLE Treatment Period | Serious Adverse event (SAE) was defined as any untoward medical occurrence that at any dose: • results in death, • is life-threatening threatening, • results in initial inpatient hospitalization or prolongation of hospitalization, •results in persistent or significant disability or incapacity, • results in a congenital anomaly/birth defect, • results in any medically significant event that did not meet any of the other 5 SAE criteria, but which was judged by a physician to potentially jeopardize the participant or require medical or surgical intervention to prevent one of the above outcomes listed as an SAE criterion. | From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Day 1 to End of Study (EOS) Visit (Month 42) in the OLE Treatment Period | Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies (ZX008-1501/ZX008-1502, and ZX008-1504 Cohort 2). Participants in 1504- Cohort 1 and de novo participants (who entered 1503 without having been in any of the core studies) did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Day 1 to EOS was divided by the total number of days from Day 1 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day convulsive seizure frequency (CSF). The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| UCB Cares | 001 844 599 2273 | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Children's Hospital | Phoenix | Arizona | 85016 | United States | ||
| Center for Neurosciences - Tucson |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40072476 | Result | Scheffer IE, Nabbout R, Lagae L, Devinsky O, Auvin S, Thiele EA, Wirrell EC, Polster T, Specchio N, Pringsheim M, Imai K, Lock MD, Langlois M, Roper RZ, Lothe A, Sullivan J. Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome. Epilepsia. 2025 Jun;66(6):1919-1932. doi: 10.1111/epi.18342. Epub 2025 Mar 12. | |
| 34768178 |
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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. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, 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 prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
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.
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.
The Participant Flow refers to the Safety (SAF) Population.
The study started to enroll participants in Jun 2016 and concluded in Jan 2023. Participants who completed 14 weeks treatment in any of the core studies ZX008-1501/ZX008-1502 (NCT02682927), or ZX008-1504 (NCT02926898) Cohort 2, or completed ZX008-1504 Cohort 1 study, and de novo participants were eligible to participate in this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Not Treated | Participant (de novo) signed the informed consent form (ICF) but never received any study medication during the study. |
| FG001 | Any ZX008 Open Label Dose | Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Enrollment |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 3, 2020 | Jul 7, 2023 |
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| From Day 1 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core) |
| Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Month 2 to EOS (Month 42) in the OLE Treatment Period | Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies. Participants in 1504-Cohort 1 and de novo participants did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Month 2 to EOS was divided by the total number of days from Month 2 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF. The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant. | From Month 2 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core) |
| Convulsive Seizure Frequency (CSF) Per 28 Days During the OLE Treatment Period (to Month 36) | Monthly (28 day) CSF was based on electronic diary data obtained for each participant. The total number of convulsive seizures in the ith interval (CSF in OLE, where, i=1, 2, 3, … , 14 ) was divided by the total number of days in the ith interval with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF of OLE. | At Month 1, Month 2, Month 3, Month 4-6, Month 7-9, Month 10-12, Month 13-15, Month 16-18, Month 19-21, Month 22-24, Month 25-27, Month 28-30, Month 31-33, and Month 34-36 |
| Convulsive Seizure Frequency (CSF) by Mean Daily Dose During the Overall OLE Treatment Period | Convulsive seizure frequency over time, reported as per 28 days was analyzed by the actual dose administered. Participants were grouped into low (0.2 to <0.4 mg/kg), medium (0.4 to <0.6 mg/kg), and high dose (>0.6 mg/kg) groups depending on their mean daily doses of ZX008 during the OLE Treatment period. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28. The convulsive seizure frequency was calculated from all available data collected. | From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42) |
| Percentage of Participants With Changes in Antiepileptic Drug (AED) Medications During First 6 Months of OLE Treatment Period | Participants in the study were required to be on stable background therapy for the first 6 months of treatment, after which background AEDs could be reduced or withdrawn so long as one background AED remained. The percentage of participants who had changes in dose or type of concomitant AED medications during the first, second, third, fourth, fifth, and sixth months were analyzed and reported. | At Month 1, 2, 3, 4 , 5, and 6 of OLE Treatment Period |
| Tucson |
| Arizona |
| 85718 |
| United States |
| Children's Hospital of Orange County | Orange | California | 92868 | United States |
| Rady Children's Hospital San Diego | San Diego | California | 92123 | United States |
| University of California San Francisco | San Francisco | California | 94158 | United States |
| The Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
| NW FL Clinical Research Group, LLC | Gulf Breeze | Florida | 32561 | United States |
| Miami Children's Hospital Brain Institute | Miami | Florida | 33155 | United States |
| Neurology and Epilepsy Research Center | Orlando | Florida | 32819 | United States |
| Clinical Integrative Research Center of Atlanta, Panda Neurology | Atlanta | Georgia | 30328 | United States |
| Ann and Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois | 60611 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Children's Hospital Of Michigan | Detroit | Michigan | 48201 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Minnesota Epilepsy Group, P.A. | Saint Paul | Minnesota | 55102 | United States |
| Institute of Neurology and Neurosurgery at St. Barnabus | Livingston | New Jersey | 07039 | United States |
| University Hospitals Cleveland Medical Center | Cleveland | Ohio | 44103 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Le Bonheur Children's Hospital | Memphis | Tennessee | 38103 | United States |
| Cook Children's Medical Center | Fort Worth | Texas | 76104 | United States |
| University of Utah | Salt Lake City | Utah | 84113 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| MultiCare Institute for Research & Innovation | Tacoma | Washington | 98405 | United States |
| Melbourne Brain Centre Austin Hospital | Heidelberg | Australia |
| Children's Health Queensland Hospital and Health Service at Lady Cilento Children's Hospital | South Brisbane | Australia |
| The Children's Hospital Westmead Dept. of Neurology and Neurosurgery | Westmead | Australia |
| Universitair Ziekenhuis Antwerpen | Edegem | Belgium |
| Centre Hospitalier Universitaire Sainte-Justine | Montreal | Canada |
| British Columbia Children's Hospital | Vancouver | Canada |
| Danish National Epilepsy Centre | Dianalund | Denmark |
| CHU Amiens-Picardie Service De Neurologie Pediatrique | Amiens | France |
| CHU De Bordeaux Service De Pédiatrie Médicale | Bordeaux | France |
| CHRU Lille Antenne Pédiatrique Du CIC - Hôpital Jeanne De Flandre | Lille | France |
| HOPITAL DEL LA TIMONE - HOPITAL HENRI GASTAUT Hôpital De La Timone Neurologie Pédiatrique Pneumologie Pédiatrique Et Médecine Infantile | Marseille | France |
| Hôpital Robert Debré Pôle: Pédiatrie Médicale Service: Neurologie Et Maladies Métaboliques | Paris | France |
| Hôpital Universitaire Necker-Enfants Malades Service de neurologie pédiatrique Centre de référence épilepsies rares (CReER) | Paris | France |
| DRK Kliniken Berlin - Westend Epilepsiezentrum / Neuropaediatrie | Berlin | Germany |
| Krankenhaus Mara Epilepsie-Zentrum Bethel | Bielefeld | Germany |
| Universitaetsklinikum Freiburg Zentrum fuer Kinder- und Jugendmedizin | Freiburg im Breisgau | Germany |
| Universitaetsklinikum Jena Klinik fuer Kinder- und Jugendmedizin Neuropaediatrie | Jena | Germany |
| Universitaetsklinikum Schleswig-Holstein Campus Kiel Klinik fuer Neuropaediatrie | Kiel | Germany |
| Kleinwachau Saechsisches Epilepsiezentrum Radeberg gemeinnuetzige GmbH | Radeberg | Germany |
| Universitaetsklinik fuer Kinder- und Jugendmedizin Abteilung III | Tübingen | Germany |
| Schoen Klinik Vogtareuth Neuropaediatrie und Neurologische Rehabilitation, Epilepsiezentrum fuer Kinder und Jugendlische, Tagesklinik fuer Neuropaediatrie | Vogtareuth | Germany |
| AOU Anna Meyer Clinica di Neurologia Pediatrica | Florence | Italy |
| Istituto Pediatrico Giannina Gaslini Dipartimento di Neurologia | Genova | Italy |
| A.O. Carlo Poma | Mantua | Italy |
| Istituto Neurologica Carlo Besta | Milan | Italy |
| Ospedale Fatebenefratelli e Oftalmico | Milan | Italy |
| Policlinico A. Gemelli | Roma | Italy |
| U.O. Neurologia Dipartimento di Neuroscienze Ospedale Pediatrico Bambino Gesù | Roma | Italy |
| Ospedale Civile Maggiore di Borgo Trento - Ospedale della Donna e del Bambino | Verona | Italy |
| Saitama Children's Medical Center | Saitama | Japan |
| National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders | Shizuoka | Japan |
| Tokyo Women's Medical University Hospital | Tokyo | Japan |
| Kempenhaeghe | Heeze | Netherlands |
| Stichting Epilepsie Instellingen Nederland | Zwolle | Netherlands |
| Hospital Sant Joan de Déu | Barcelona | Spain |
| Hospital Ruber Internacional Primera Planta Servicio de Neurologia | Madrid | Spain |
| Clinica Universitaria de Navarra Fase 4. Segunda planta, Consulta de Pediatria | Pamplona | Spain |
| Birmingham Children Hospital NHS Foundation Trust | Birmingham | United Kingdom |
| Institute of Neurosciences Queen Elizabeth University Hospital | Glasgow | United Kingdom |
| Alder Hey Hospital | Liverpool | United Kingdom |
| Great Ormond Street Hospital for Children NHS Foundation Trust | London | United Kingdom |
| St. Thomas Hospital | London | United Kingdom |
| Sheffield Children's Hospital | Sheffield | United Kingdom |
| Cross JH, Galer BS, Gil-Nagel A, Devinsky O, Ceulemans B, Lagae L, Schoonjans AS, Donner E, Wirrell E, Kothare S, Agarwal A, Lock M, Gammaitoni AR. Impact of fenfluramine on the expected SUDEP mortality rates in patients with Dravet syndrome. Seizure. 2021 Dec;93:154-159. doi: 10.1016/j.seizure.2021.10.024. Epub 2021 Nov 2. |
| COMPLETED |
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| NOT COMPLETED |
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| Treatment |
|
|
Baseline characteristics refers to the Safety (SAF) population which included all enrolled participants who received at least one dose of ZX008 during the open label extension (OLE). As pre-specified in the SAP, participant Demographics and Baseline Characteristics were summarized for the safety population.
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| ID | Title | Description |
|---|---|---|
| BG000 | Any ZX008 Open Label Dose | Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Open-label Extension (OLE) Treatment Period | Treatment-emergent adverse events (TEAE) were defined as any AEs that based on start date information occurs after the first intake of study treatment. | Safety (SAF) population included all enrolled participants who received at least one dose of ZX008 during the OLE. | Posted | Number | percentage of participants | From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42) |
|
|
| ||||||||||||||||||||||||||
| Primary | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the OLE Treatment Period | A TEAE was defined as any AE that based on start date information occurs after the first intake of study treatment. Percentage of participants with TEAEs leading to withdrawal from IMP during OLE Treatment Period were reported. | Safety (SAF) population included all enrolled participants who received at least one dose of ZX008 during the OLE. | Posted | Number | percentage of participants | From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42) |
|
| |||||||||||||||||||||||||||
| Primary | Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) During the OLE Treatment Period | Serious Adverse event (SAE) was defined as any untoward medical occurrence that at any dose: • results in death, • is life-threatening threatening, • results in initial inpatient hospitalization or prolongation of hospitalization, •results in persistent or significant disability or incapacity, • results in a congenital anomaly/birth defect, • results in any medically significant event that did not meet any of the other 5 SAE criteria, but which was judged by a physician to potentially jeopardize the participant or require medical or surgical intervention to prevent one of the above outcomes listed as an SAE criterion. | Safety (SAF) population included all enrolled participants who received at least one dose of ZX008 during the OLE. | Posted | Number | percentage of participants | From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42) |
| ||||||||||||||||||||||||||||
| Secondary | Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Day 1 to End of Study (EOS) Visit (Month 42) in the OLE Treatment Period | Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies (ZX008-1501/ZX008-1502, and ZX008-1504 Cohort 2). Participants in 1504- Cohort 1 and de novo participants (who entered 1503 without having been in any of the core studies) did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Day 1 to EOS was divided by the total number of days from Day 1 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day convulsive seizure frequency (CSF). The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant. | Modified Intent-to-Treat (mITT) population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE. | Posted | Median | Full Range | seizure frequency per 28 days | From Day 1 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core) |
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| Secondary | Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Month 2 to EOS (Month 42) in the OLE Treatment Period | Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies. Participants in 1504-Cohort 1 and de novo participants did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Month 2 to EOS was divided by the total number of days from Month 2 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF. The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant. | mITT population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE. Here, number of participants analyzed included those participants who were evaluable for the assessment. | Posted | Median | Full Range | seizure frequency per 28 days | From Month 2 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core) |
| |||||||||||||||||||||||||||
| Secondary | Convulsive Seizure Frequency (CSF) Per 28 Days During the OLE Treatment Period (to Month 36) | Monthly (28 day) CSF was based on electronic diary data obtained for each participant. The total number of convulsive seizures in the ith interval (CSF in OLE, where, i=1, 2, 3, … , 14 ) was divided by the total number of days in the ith interval with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF of OLE. | mITT population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE. Here, number analyzed signifies participants who were evaluable at specified time points. | Posted | Median | Full Range | seizure frequency per 28 days | At Month 1, Month 2, Month 3, Month 4-6, Month 7-9, Month 10-12, Month 13-15, Month 16-18, Month 19-21, Month 22-24, Month 25-27, Month 28-30, Month 31-33, and Month 34-36 |
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| Secondary | Convulsive Seizure Frequency (CSF) by Mean Daily Dose During the Overall OLE Treatment Period | Convulsive seizure frequency over time, reported as per 28 days was analyzed by the actual dose administered. Participants were grouped into low (0.2 to <0.4 mg/kg), medium (0.4 to <0.6 mg/kg), and high dose (>0.6 mg/kg) groups depending on their mean daily doses of ZX008 during the OLE Treatment period. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28. The convulsive seizure frequency was calculated from all available data collected. | mITT population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE. Here, number analyzed represents the number of participants categorized by mean daily dose. | Posted | Median | Full Range | seizure frequency per 28 days | From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42) |
| |||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Changes in Antiepileptic Drug (AED) Medications During First 6 Months of OLE Treatment Period | Participants in the study were required to be on stable background therapy for the first 6 months of treatment, after which background AEDs could be reduced or withdrawn so long as one background AED remained. The percentage of participants who had changes in dose or type of concomitant AED medications during the first, second, third, fourth, fifth, and sixth months were analyzed and reported. | mITT population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE. | Posted | Number | percentage of participants | At Month 1, 2, 3, 4 , 5, and 6 of OLE Treatment Period |
|
From Day 1 up to 42 months
A TEAE was defined as any AE that based on start date information occurs after the first intake of study treatment. The Safety (SAF) population was the set of all enrolled subjects who received at least one dose of ZX008 during the OLE. As pre-specified in the SAP, safety analyses were performed on the SAF Population.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Any ZX008 Open Label Dose | Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period. | 3 | 374 | 99 | 374 | 342 | 374 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block second degree | Cardiac disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Diarrhoea haemorrhagic | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Duodenal perforation | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Enterovesical fistula | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Tooth disorder | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Abasia | General disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Hypothermia | General disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Impaired healing | General disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Sudden unexplained death in epilepsy | General disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Bronchitis viral | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Enterovirus infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Epididymitis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Epstein-Barr virus infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Helicobacter infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Infectious mononucleosis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Otitis media acute | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Respiratory syncytial virus infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Varicella | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Viral pharyngitis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Abdominal injury | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Drug dose omission | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Foreign body aspiration | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Near drowning | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Blood glucose decreased | Investigations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Heart rate decreased | Investigations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Feeding intolerance | Metabolism and nutrition disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Hyperammonaemia | Metabolism and nutrition disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Aneurysmal bone cyst | Musculoskeletal and connective tissue disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Change in seizure presentation | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Dystonia | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Febrile convulsion | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Hyperkinesia | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Hypotonia | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Movement disorder | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Myoclonus | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Petit mal epilepsy | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Seizure cluster | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Status epilepticus | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Acute psychosis | Psychiatric disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Apathy | Psychiatric disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Tic | Psychiatric disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Labial frenectomy | Surgical and medical procedures | MedDRA version 19.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Blood glucose decreased | Investigations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Echocardiogram abnormal | Investigations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Abnormal behaviour | Psychiatric disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 19.0 | Non-systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| UCB | Cares | 001 844 599 2273 | UCBCares@ucb.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 4, 2020 | Jul 7, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D004831 | Epilepsies, Myoclonic |
| D012640 | Seizures |
| D004827 | Epilepsy |
| D001927 | Brain Diseases |
| ID | Term |
|---|---|
| D004829 | Epilepsy, Generalized |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000073376 | Epileptic Syndromes |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D005277 | Fenfluramine |
| ID | Term |
|---|---|
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
Not provided
Not provided
| Family Decision |
|
| IP approved and subject moved to commercial drug |
|
| Lack of Efficacy |
|
| Non-Compliance With E-Diary |
|
| Physician Decision |
|
| Subject has transitioned to study 1900 OLE study |
|
| Subject needed to take prohibited medication |
|
| Subject transferred to direct access programme |
|
| Switching to commercially available drug |
|
| Transitioned to commercial supply of medication |
|
| Withdrawal By Caregiver |
|
| Withdrawal by sponsor due to lack of compliance |
|
| Withdrawal by Subject |
|
| Reason unknown |
|
| >18 years |
|
| Asian |
|
| American Indian or Alaska Native |
|
| Other |
|
| Not Reported |
|
| Not Reported |
|
| Unknown |
|
| Participants |
|
|
|
|
|
|
|
|
|
|
|
|
| Units | Counts |
|---|
| Participants |
|
|