CDDPhase 2NCT03861871
Fenfluramine in CDKL5 Deficiency Disorder (CDD)
A Phase 2 study testing Fenfluramine Hydrochloride in people with CDD, run by NYU Langone Health at 1 site in United States.
Trial summary
This study will be enrolling 10 patients, ages 2-18 years old, with a confirmed genetic/clinical diagnosis of CDKL5 Deficiency Disorder (CDD) in an open label trial of fenfluramine for seizure control. Patients will be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d). Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- CDD
- What is being tested?
- Fenfluramine Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Oct 2019to 24 Oct 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Confirmed clinical/genetic diagnosis of CDKL5 Deficiency Disorder CDD
- Ages 2-18 years old. 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 30 days after the last dose of study drug.
- Subject has been informed of the nature of the study and informed consent has been obtained from the legally responsible parent/guardian.
- Subject has provided assent in accordance with Investigational Review Board/Independent Ethics Committee (IRB/IEC) requirements, if capable.
- Subject's caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.
- Subjects must be receiving a therapeutically relevant and stable dose of anti-seizure medications, dietary therapies for epilepsy or vagus nerve stimulation settings for at least 4 weeks prior to screening and are expected to remain stable throughout the study.
- ≥4 convulsive seizures (tonic-clonic, tonic, atonic, clonic, focal motor) per 4-week period; each convulsive seizure must last ≥3 seconds.
Who cannot join
- Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication.
- Subject has current or past history of cardiovascular or cerebrovascular disease, myocardial infarction or stroke.
- Subject has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke, or clinically significant structural cardiac abnormality, including but not limited to mitral valve prolapse, atrial or ventricular septal defects, patent ductus arteriosis, and patent foramen ovale with reversal of shunt. (note: Patent foramen ovale or a bicuspid valve are is not considered exclusionary, but may be associated with the following diseases, which are exclusionary: coarctation of the aorta, Turner syndrome, supravalvular aortic stenosis, subvalvular aortic stenosis, patent ductus arteriosus, Sinus of Valsalva aneurysm, ventricular septal defect, Shone's complex, ascending aortic aneurysm, Loeys-Dietz syndrome, ACTA2 mutation familial thoracic aortic aneurysm syndrome, and MAT2A mutation familial thoracic aortic aneurysm syndrome).
- Subject has current or recent history of Anorexia Nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month.
- Subjects who are currently on CBD/THC or any MMJ or those who have tested positive urine tetrahydrocannabinol (THC) Panel or whole blood cannabidiol (CBD).
- Subject has participated in another clinical trial within the past 30 days (calculated from that study's last scheduled visit).
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- Subject is at imminent risk of self-harm or harm to others, in the investigator's opinion, based on clinical interview.
- Subject has a current or past history of glaucoma.
- 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; or cyproheptadine. (see appendix 1)
- Subject has moderate or severe hepatic impairment. Asymptomatic subjects with mild hepatic impairment (elevated liver enzymes <3x upper limited of normal [ULN] and/or elevated bilirubin <2x ULN) may be entered into the study after review and approval by the Medical Monitor in conjunction with the sponsor, in consideration of comorbidities and concomitant medications.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York Langone Health Comprehensive Epilespy Center
New York, New York, 10016
About this study
Official title: Fenfluramine in CKDL5 Deficiency Disorder (CDD)
This study will be enrolling 10 patients, ages 2-18 years old, with a confirmed genetic/clinical diagnosis of CDKL5 Deficiency Disorder (CDD) in an open label trial of fenfluramine for seizure control. Patients will be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
- Conditions
- CDD
- Being tested
- Fenfluramine Hydrochloride
- Keywords
- CKDL5 Deficiency Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fenfluramine HydrochlorideDrug
Also called ZX008
Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
| Study group | Role | What they receive |
|---|---|---|
| Fenfluramine Hydrochloride | Experimental | Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication. Receives: Drug: Fenfluramine Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Median Monthly Convulsive Seizure Frequency
Change between baseline and Week 14 in the median number of monthly convulsive seizures.
Measured: Baseline, Week 14
Secondary outcomes (4)
Change in Caregiver Global Impression of Change (CGIC) Score
The CGIC is a 1-item, parent/caregiver-completed assessment used determine how much their child/care-recipient has improved with treatment. The instrument asks parents/caregivers to rate their child's/care-recipient's improvement as: 1) very much improved; 2) much improved; 3) minimally improved; 4) unchanged; 5) a little worse; 6) much worse; 7) very much worse; the total score correspondingly ranges from 1-7.
Measured: Baseline, Week 14
Change in Investigator Global Impression of Change (IGIC) Score
The IGIC is a 1-item, investigator-completed assessment used determine how much a patient has improved with treatment. The instrument asks the investigator to rate patients' improvement as: 1) very much improved; 2) much improved; 3) minimally improved; 4) unchanged; 5) a little worse; 6) much worse; 7) very much worse; the total score correspondingly ranges from 1-7.
Measured: Baseline, Week 14
Change in Quality of Life in Childhood Epilepsy (QOLCE) Score
Parent/caregiver-completed assessment assessing how epilepsy affects day-to-day functioning of their child/care-recipient in various life areas. Each item is ranked on a 5-point Likert scale from 1 (response correlated with the lowest possible quality of life) to 5 (response correlated with the highest possible quality of life). Item scores are then transformed to a 0-100 scale as follows: 1 = 0, 2 = 25, 3 = 50, 4=75, and 5=100. The total score is the average of all item scores and ranges from 0-100. Higher scores indicate greater quality of life; an increase in scores indicates quality of life increased during the observational period.
Measured: Baseline, Week 14
Change in Pediatric Quality Of Life (PEDS-QL) Epilepsy Module Raw Score
The PedsQL Epilepsy Module is a 29-item measure with five scales: Impact, Cognitive, Sleep, Executive Function, and Mood/Behavior. The Impact scale (nine items) assesses how epilepsy interferes with daily activities, interacting with peers, independence, and increased disease burden due to treatment. The Cognitive Scale (six items) assesses memory, ability to learn new materials, school-related difficulties, and reading difficulties. The Sleep Scale (three items) assesses fatigue and sleep difficulties. The Executive Function Scale (six items) assesses organization, task initiation, impulsivity, and inattention. The Mood/Behavior Scale (five items) assesses feelings of anger, sadness, worries, and frustration tolerance. Scores range from 0-100 for each subscale, with higher scores representing better quality of life. The raw score is the sum of each subscale score and ranges from 0-500.
Measured: Baseline, Week 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2019
- Study start29 Oct 2019
- Primary completion30 Aug 2022
- Study completion24 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CDDStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Orrin Devinsky, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03861871
- Sponsor's protocol ID
- 18-01530
- Status last verified
- Sep 2023
- First submitted
- 1 Mar 2019
- Last updated
- 4 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Devinsky O, King L, Schwartz D, Conway E, Price D. Effect of fenfluramine on convulsive seizures in CDKL5 deficiency disorder. Epilepsia. 2021 Jul;62(7):e98-e102. doi: 10.1111/epi.16923. Epub 2021 May 12.
PubMed 33979451
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fenfluramine in CKDL5 Deficiency Disorder (CDD)
- ClinicalTrials.gov ID
- NCT03861871
- Acronym / sponsor ID
- 18-01530
- Conditions
- CDD
- Keywords
- CKDL5 Deficiency Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- 29 Oct 2019 (actual)
- Primary completion
- 30 Aug 2022 (actual)
- Study completion
- 24 Oct 2022 (actual)
- First posted
- 4 Mar 2019 (actual)
- Results
- Posted 4 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be enrolling 10 patients, ages 2-18 years old, with a confirmed genetic/clinical diagnosis of CDKL5 Deficiency Disorder (CDD) in an open label trial of fenfluramine for seizure control. Patients will be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fenfluramine Hydrochloride | Experimental | Drug: Fenfluramine HydrochlorideStudy medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart. Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d). After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart. After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Confirmed clinical/genetic diagnosis of CDKL5 Deficiency Disorder CDD
- Ages 2-18 years old. 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 30 days after the last dose of study drug.
- Subject has been informed of the nature of the study and informed consent has been obtained from the legally responsible parent/guardian.
- Subject has provided assent in accordance with Investigational Review Board/Independent Ethics Committee (IRB/IEC) requirements, if capable.
- Subject's caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.
Key exclusion criteria (10 listed)
- Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication.
- Subject has current or past history of cardiovascular or cerebrovascular disease, myocardial infarction or stroke.
- Subject has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke, or clinically significant structural cardiac abnormality, including but not limited to mitral valve prolapse, atrial or ventricular septal defects, patent ductus arteriosis, and patent foramen ovale with reversal of shunt. (note: Patent foramen ovale or a bicuspid valve are is not considered exclusionary, but may be associated with the following diseases, which are exclusionary: coarctation of the aorta, Turner syndrome, supravalvular aortic stenosis, subvalvular aortic stenosis, patent ductus arteriosus, Sinus of Valsalva aneurysm, ventricular septal defect, Shone's complex, ascending aortic aneurysm, Loeys-Dietz syndrome, ACTA2 mutation familial thoracic aortic aneurysm syndrome, and MAT2A mutation familial thoracic aortic aneurysm syndrome).
- Subject has current or recent history of Anorexia Nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month.
- Subjects who are currently on CBD/THC or any MMJ or those who have tested positive urine tetrahydrocannabinol (THC) Panel or whole blood cannabidiol (CBD).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fenfluramine HydrochlorideAlso: ZX008Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited. | Drug | Fenfluramine Hydrochloride |
Primary outcome
Change From Baseline in Median Monthly Convulsive Seizure Frequency
Time frame: Baseline, Week 14
Change between baseline and Week 14 in the median number of monthly convulsive seizures.
4 secondary outcomes
Change in Caregiver Global Impression of Change (CGIC) Score
Time frame: Baseline, Week 14
Change in Investigator Global Impression of Change (IGIC) Score
Time frame: Baseline, Week 14
Change in Quality of Life in Childhood Epilepsy (QOLCE) Score
Time frame: Baseline, Week 14
Change in Pediatric Quality Of Life (PEDS-QL) Epilepsy Module Raw Score
Time frame: Baseline, Week 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33979451Devinsky O, King L, Schwartz D, Conway E, Price D. Effect of fenfluramine on convulsive seizures in CDKL5 deficiency disorder. Epilepsia. 2021 Jul;62(7):e98-e102. doi: 10.1111/epi.16923. Epub 2021 May 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Orrin Devinsky, MD principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fenfluramine Hydrochloride in people with CDD, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Median Monthly Convulsive Seizure Frequency (time frame: Baseline, Week 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03861871, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2023.