A Phase 3 Study to Examine the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder.

NCT05064878 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: ZX008-2103/EP02162021-003222-762023-506269-78-00
• Study Type: interventional
• Target: 87
• Locations: 14 countries
• Sites: 46

Brief Summary

This is a Phase 3 Study to examine the efficacy and safety of ZX008 in children and adults with cyclin-dependent kinase like-5 (CDKL5) deficiency disorder (CDD).

Conditions

Generalized Tonic Clonic Seizure; Epileptic Spasm; Refractory Seizures; CDKL5 Deficiency Disorder

Keywords

CDD; CDKL5; fenfluramine

Outcome Measures

Primary Outcomes (22)

• Percentage Change from Baseline in Countable Motor Seizure Frequency (CMSF) (Part 1)

  The median percentage change from the Baseline in monthly (per 28 days) CMSF during the combined Titration and Maintenance Periods with the fenfluramine (ZX008) 0.8 mg/kg/day group compared with the placebo group will be reported.

  Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)

• Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 2)

  An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Treatment Emergent Adverse Events (TEAEs) are defined as any AEs reported on or after the first dose of study medication.

  Up to OLE1 Treatment Period Post-Dose Safety Follow-up Visit 17 (up to 70 weeks)

• Percentage of Participants With Abnormal Physical Examination Findings (Part 2)

  Abnormal findings of physical exam that is considered clinically significant by Principal Investigator (PI).

  Up to End of Treatment (EoT)/Early Termination (ET) Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Percentage of Participants With Abnormal Neurological Examination Findings (Part 2)

  Abnormal findings of neurological exam that is considered clinically significant by PI.

  Up to EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Percentage of Participants with Positive Response to Self-harm Question (Part 2)

  OLE1 Treatment Period Day 1 to OLE1 Treatment Period Post-Dose Safety Follow-up Visit 17 (up to 70 weeks)

• Percentage of Participants with Increase in Valvular Regurgitation from Baseline (except absent to trace) (Part 2)

  Valvular regurgitation will be assessed using a 2-dimensional (2-D) Color Doppler Echocardiography (ECHO).

  Baseline (28 days), Cardiac Follow-up Visit 18 (up to 96 weeks)

• Percentage of Participants with Pulmonary Arterial Hypertension (PASP > 35 mmHg) at any Time During Treatment on Repeat Testing (Part 2)

  OLE1 Treatment Period Day 1 to EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Laboratory Parameters (Hematology) (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Laboratory Parameters (Hormones) (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Laboratory parameters (Chemistry) (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Laboratory Parameters (Urinalysis) (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Vital Signs (Blood pressure) (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Vital Signs (Heart rate) (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Vital Signs (Temperature) (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Vital Signs (Respiratory rate) (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Body Weight (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Change from Baseline in Tanner Staging (Part 2)

  Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)

• Percentage of Participants with TEAEs (Part 3)

  An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Treatment Emergent Adverse Events are defined as any AEs reported on or after the first dose of study medication.

  Up to OLE2 Period Post-Dose Safety Follow-up (up to 200 weeks)

• Change from Baseline in Height (Part 3)

  Baseline (28 days), OLE2 Period EoT/ET Visit 23 (up to 198 weeks)

• Change from Baseline in Body Weight (Part 3)

  Baseline (28 days), OLE2 Period EoT/ET Visit 23 (up to 198 weeks)

• Percentage of Participants with Increase in Valvular Regurgitation from Baseline (except absent to trace) (Part 3)

  Valvular regurgitation will be assessed using a 2 D Color Doppler ECHO.

  Baseline (28 days), Cardiac Follow-up Visit (up to 295 weeks)

• Percentage of Participants with Pulmonary Arterial Hypertension (PASP > 35 mmHg) at any Time During Treatment on Repeat Testing (Part 3)

  OLE2 Period Day 1 to EoT/ET Visit 23 of OLE2 Period (up to 198 weeks)

Secondary Outcomes (35)

• Percentage of Participants Who Achieve a ≥ 50% Reduction from Baseline in CMSF (Part 1)

  Baseline (28 days), Combined T+M Periods (14 weeks)

• Percentage of Participants with a Clinical Global Impression-Improvement (CGI-I) Rating of 'Much Improved' or 'Very Much Improved' as Assessed by Investigator (Part 1)

  At the end of the combined T+M Periods (14 weeks)

• Percentage Change From Baseline in Monthly Generalized Tonic-Clonic (GTC) Seizure Frequency (Part 1)

  Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)

• Categorized Percentage Change in Seizures from Baseline in CMSF (Part 1)

  Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)

• Percentage of Participants who Achieve "Near Seizure Freedom" (Part 1)

  Combined T+M Periods (14 weeks)

Study Arms (3)

Fenfluramine (hydrochloride) 0.8 mg/kg/day

EXPERIMENTAL

Part 1: Fenfluramine (hydrochloride) 0.8 mg/kg/day will be administered twice a day (BID) in equally divided doses; maximum of 30 mg/day, (subjects taking concomitant stiripentol will receive 0.5 mg/kg/day, \[maximum of 20 mg/day\]) with or without food.

Drug: Fenfluramine

Placebo

PLACEBO COMPARATOR

Part 1: Matching fenfluramine (hydrochloride) placebo will be administered twice a day (BID) in equally divided doses with or without food.

Drug: Placebo

Fenfluramine (hydrochloride) Open-label

EXPERIMENTAL

Part 2 and Part 3: Open-label fenfluramine (hydrochloride) will be administered using a flexible dosing regimen, up to fenfluramine 0.8 mg/kg/day; maximum dose: 30 mg/day (subjects taking concomitant stiripentol will receive 0.5 mg/kg/day, \[maximum of 20 mg/day\]). Fenfluramine (hydrochloride) will be administered twice a day (BID) in equally divided doses with or without food.

Drug: Fenfluramine

Interventions

Fenfluramine DRUG

Fenfluramine is supplied as an oral aqueous solution of fenfluramine hydrochloride.

Also known as: FINTEPLA, ZX008, fenfluramine HCl, fenfluramine hydrochloride

Fenfluramine (hydrochloride) 0.8 mg/kg/day; Fenfluramine (hydrochloride) Open-label

Placebo DRUG

Matching fenfluramine (hydrochloride) placebo is supplied as an oral solution.

Placebo

Eligibility Criteria

• Age: 1 Year - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject has a confirmed pathogenic or likely pathogenic mutation in the CDKL5 gene and a clinical diagnosis of CDKL5 deficiency disorder (CDD) with epilepsy onset in the first year of life, plus motor and developmental delays.
• Subject is male or female, aged 1 to 35 years, inclusive, as of the day of the Screening Visit.
• Subject must have failed to achieve seizure control despite previous or current use of 2 or more antiepileptic treatments (AETs).
• Subject is currently receiving at least 1 concomitant antiseizure treatment: antiseizure medication (ASM), vagus nerve stimulation (VNS), responsive neurostimulation (RNS), or ketogenic diet (KD).
• All medications or interventions for epilepsy (including VNS, RNS, and KD) must be stable prior to screening and are expected to remain stable throughout the study.
• At the Screening Visit, parent/caregiver reports that subject has ≥ 4 countable motor seizures (CMS) per week.

You may not qualify if:

• Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study drug.
• Subject has a diagnosis of pulmonary arterial hypertension.
• Subject has a clinically significant medical condition, including chronic obstructive pulmonary disease, interstitial lung disease, or portal hypertension, or has had clinically relevant symptoms or a clinically significant illness currently or in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.
• Subject has current eating disorder that suggests anorexia nervosa or bulimia.
• Subject has a current or past history of glaucoma.
• Subject is taking \> 4 concomitant antiseizure medications (ASMs). Rescue medications are not included in the count.
• Subject is receiving concomitant treatment with cannabidiol (CBD) other than Epidiolex/Epidyolex or is being actively treated with tetrahydrocannabinol (THC) or any marijuana product for any condition.
• Subject has moderate to severe hepatic impairment.
• Subject is currently receiving another investigational product(s) or has received another investigational product within 30 days or within \< 5 times the half-lives of the investigational product, whichever is longer, prior to the Screening Visit.
• Subject has previously been treated with Fintepla® (fenfluramine) prior to the Screening Visit.

Sponsors & Collaborators

• Zogenix, Inc.: lead

Study Sites (46)

Ep0216 154

Birmingham, Alabama, 35233, United States

Location

Ep0216 144

Los Angeles, California, 90095, United States

Location

Ep0216 101

San Francisco, California, 94158, United States

Location

Ep0216 173

Aurora, Colorado, 80045, United States

Location

Ep0216 149

Washington D.C., District of Columbia, 20010, United States

Location

Ep0216 157

Atlanta, Georgia, 30329, United States

Location

Ep0216 113

Brookline, Massachusetts, 02115, United States

Location

Ep0216 134

Detroit, Michigan, 48201, United States

Location

Ep0216 166

Chapel Hill, North Carolina, 27514, United States

Location

Ep0216 164

Cleveland, Ohio, 44195, United States

Location

Ep0216 120

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Ep0216 124

Memphis, Tennessee, 38105, United States

Location

Ep0216 171

Austin, Texas, 78731, United States

Location

Ep0216 2505

Linz, Austria

Location

Ep0216 804

Brussels, Belgium

Location

Ep0216 801

Edegem, Belgium

Location

Ep0216 2802

Tbilisi, Georgia

Location

Ep0216 902

Bielefeld, Germany

Location

Ep0216 909

Kehl-kork, Germany

Location

Ep0216 908

Kiel, Germany

Location

Ep0216 901

Vogtareuth, Germany

Location

Ep0216 1803

Dublin, Ireland

Location

Ep0216 1909

Petah Tikva, Israel

Location

Ep0216 1906

Ramat Gan, Israel

Location

Ep0216 1904

Tel Aviv, Israel

Location

Ep0216 1201

Florence, Italy

Location

Ep0216 1204

Genova, Italy

Location

Ep0216 1212

Modena, Italy

Location

Ep0216 1206

Roma, Italy

Location

Ep0216 1208

Roma, Italy

Location

Ep0216 1202

Verona, Italy

Location

Ep0216 1512

Hiroshima, Japan

Location

Ep0216 1505

Niigata, Japan

Location

Ep0216 1518

Omura-shi, Japan

Location

Ep0216 1502

Shizuoka, Japan

Location

Ep0216 1401

Zwolle, Netherlands

Location

Ep0216 2104

Lisbon, Portugal

Location

Ep0216 2105

Porto, Portugal

Location

Ep0216 1103

Barcelona, Spain

Location

Ep0216 1117

Madrid, Spain

Location

Ep0216 1118

Santiago de Compostela, Spain

Location

Ep0216 3101

Dubai, United Arab Emirates

Location

Ep0216 607

Bristol, United Kingdom

Location

Ep0216 602

London, United Kingdom

Location

Ep0216 611

Manchester, United Kingdom

Location

Ep0216 604

Sheffield, United Kingdom

Location

MeSH Terms

Conditions

CDKL5 deficiency disorder; Epilepsy, Tonic-Clonic; Spasms, Infantile; Seizures

Interventions

Fenfluramine

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• UCB Cares

  001 844 599 2273

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2021
• First Posted: October 1, 2021
• Study Start: March 8, 2022
• Primary Completion (Estimated): November 8, 2027
• Study Completion (Estimated): November 8, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 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.
• Access Criteria: 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.

Locations

IT (6); JP (4); AE (1); GB (4); GE (1); DE (4); US (13); AU (1); NL (1); PT (2); ES (3); BE (2); IE (1); IL (3)