Fenfluramine in CDKL5 Deficiency Disorder (CDD)

NCT03861871 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 18-01530
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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

Keywords

CKDL5 Deficiency Disorder

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Median Monthly Convulsive Seizure Frequency

  Change between baseline and Week 14 in the median number of monthly convulsive seizures.

  Baseline, Week 14

Secondary Outcomes (4)

• Change in Caregiver Global Impression of Change (CGIC) Score

  Baseline, Week 14

• Change in Investigator Global Impression of Change (IGIC) Score

  Baseline, Week 14

• Change in Quality of Life in Childhood Epilepsy (QOLCE) Score

  Baseline, Week 14

• Change in Pediatric Quality Of Life (PEDS-QL) Epilepsy Module Raw Score

  Baseline, Week 14

Study Arms (1)

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.

Drug: Fenfluramine Hydrochloride

Interventions

Fenfluramine Hydrochloride 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.

Also known as: ZX008

Fenfluramine Hydrochloride

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

New York Langone Health Comprehensive Epilespy Center

New York, New York, 10016, United States

Location

Related Publications (1)

• 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.

  PMID: 33979451 DERIVED

MeSH Terms

Interventions

Fenfluramine

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Latoya King
• Organization: NYU Langone Health

latoya.king@nyulangone.org

646 558 083

Study Officials

• Orrin Devinsky, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 4, 2019
• Study Start: October 29, 2019
• Primary Completion: August 30, 2022
• Study Completion: October 24, 2022
• Last Updated: October 4, 2023
• Results First Posted: October 4, 2023

Record last verified: 2023-09

Locations

US (1)