Fenfluramine in CDKL5 Deficiency Disorder (CDD)

NCT ID: NCT03861871

Last Updated: 2023-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-29
• Study Completion Date: 2022-10-24

Brief 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).

Conditions

CDD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fenfluramine Hydrochloride

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.

Group Type: EXPERIMENTAL

Fenfluramine Hydrochloride

Intervention Type: DRUG

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.

Interventions

Fenfluramine Hydrochloride

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.

Intervention Type: DRUG

Other Intervention Names

ZX008

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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).
• 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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Orrin Devinsky, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

New York Langone Health Comprehensive Epilespy Center

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33979451 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

18-01530

Identifier Type: -

Identifier Source: org_study_id