Active, not recruiting
Phase 3
A Phase 3 Study to Examine the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder.
Condition(s) studied
CDKL5 Deficiency DisorderGeneralized Tonic Clonic SeizureEpileptic SpasmRefractory Seizures
Investigational drug(s) / intervention(s)
FenfluraminePlacebo
Fenfluramine: Fenfluramine is supplied as an oral aqueous solution of fenfluramine hydrochloride.
Placebo: Matching fenfluramine (hydrochloride) placebo is supplied as an oral solution.
Study 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).
Eligibility
Inclusion Criteria:
* 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.
Exclusion Criteria:
* 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 or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke, severe ventricular arrhythmias, or clinically significant structural cardiac abnormality, including but not limited to mitral valve prolapse, atrial or ventricular septal defects, patent ductus arteriosus, and patent foramen ovale with reversal of shunt. (Note: Patent foramen ovale or a bicuspid aortic valve are not considered exclusionary).
* 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.
Primary outcome measure(s)
- Percentage Change from Baseline in Countable Motor Seizure Frequency (CMSF) (Part 1) — Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
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.
- Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 2) — Up to OLE1 Treatment Period Post-Dose Safety Follow-up Visit 17 (up to 70 weeks)
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.
- Percentage of Participants With Abnormal Physical Examination Findings (Part 2) — Up to End of Treatment (EoT)/Early Termination (ET) Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Abnormal findings of physical exam that is considered clinically significant by Principal Investigator (PI).
- Percentage of Participants With Abnormal Neurological Examination Findings (Part 2) — Up to EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Abnormal findings of neurological exam that is considered clinically significant by PI.
- 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) — Baseline (28 days), Cardiac Follow-up Visit 18 (up to 96 weeks)
Valvular regurgitation will be assessed using a 2-dimensional (2-D) Color Doppler Echocardiography (ECHO).
- 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) — Up to OLE2 Period Post-Dose Safety Follow-up (up to 200 weeks)
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.
- 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) — Baseline (28 days), Cardiac Follow-up Visit (up to 295 weeks)
Valvular regurgitation will be assessed using a 2 D Color Doppler ECHO.
- 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)
Trial sites (46)
| Facility | City | Region | Status |
|---|
| Ep0216 154 |
Birmingham |
Alabama |
|
| Ep0216 144 |
Los Angeles |
California |
|
| Ep0216 101 |
San Francisco |
California |
|
| Ep0216 173 |
Aurora |
Colorado |
|
| Ep0216 149 |
Washington D.C. |
District of Columbia |
|
| Ep0216 157 |
Atlanta |
Georgia |
|
| Ep0216 113 |
Brookline |
Massachusetts |
|
| Ep0216 134 |
Detroit |
Michigan |
|
| Ep0216 166 |
Chapel Hill |
North Carolina |
|
| Ep0216 164 |
Cleveland |
Ohio |
|
| Ep0216 120 |
Philadelphia |
Pennsylvania |
|
| Ep0216 124 |
Memphis |
Tennessee |
|
| Ep0216 171 |
Austin |
Texas |
|
| Ep0216 2505 |
Linz |
Austria |
|
| Ep0216 804 |
Brussels |
Belgium |
|
| Ep0216 801 |
Edegem |
Belgium |
|
| Ep0216 2802 |
Tbilisi |
Georgia |
|
| Ep0216 902 |
Bielefeld |
Germany |
|
| Ep0216 909 |
Kehl-kork |
Germany |
|
| Ep0216 908 |
Kiel |
Germany |
|
| Ep0216 901 |
Vogtareuth |
Germany |
|
| Ep0216 1803 |
Dublin |
Ireland |
|
| Ep0216 1909 |
Petah Tikva |
Israel |
|
| Ep0216 1906 |
Ramat Gan |
Israel |
|
| Ep0216 1904 |
Tel Aviv |
Israel |
|
| Ep0216 1201 |
Florence |
Italy |
|
| Ep0216 1204 |
Genova |
Italy |
|
| Ep0216 1212 |
Modena |
Italy |
|
| Ep0216 1206 |
Roma |
Italy |
|
| Ep0216 1208 |
Roma |
Italy |
|
| Ep0216 1202 |
Verona |
Italy |
|
| Ep0216 1512 |
Hiroshima |
Japan |
|
| Ep0216 1505 |
Niigata |
Japan |
|
| Ep0216 1518 |
Omura-shi |
Japan |
|
| Ep0216 1502 |
Shizuoka |
Japan |
|
| Ep0216 1401 |
Zwolle |
Netherlands |
|
| Ep0216 2104 |
Lisbon |
Portugal |
|
| Ep0216 2105 |
Porto |
Portugal |
|
| Ep0216 1103 |
Barcelona |
Spain |
|
| Ep0216 1117 |
Madrid |
Spain |
|
+ 6 more sites — see the full list on the official registry below.