Trial Outcomes & Findings for A 2-Part Study to Investigate the Dose-Ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children ≥ 2 Years Old and Young Adults With Dravet Syndrome (NCT NCT02926898)

Last Updated: 2022-11-02

Results Overview

Monthly (28 day) convulsive seizure frequency (CSF) was based on electronic diary data obtained for each participant. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). The number of convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day CSF.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

87 participants

Primary outcome timeframe

15 weeks (combined Titration + Maintenance Period)

Results posted on

2022-11-02

Participant Flow

A total of 28 study sites in Canada, France, Germany, the Netherlands, Spain, the United Kingdom, and the United States enrolled participants for Study 1504 Cohort 2.

A total of 115 subjects were screened for eligibility to participate in Study 1504 Cohort 2. Of these, 87 subjects were enrolled and randomized.

Participant milestones

Participant milestones
Measure	Cohort 2: ZX008 0.5 mg/kg/Day ZX008 0.5 mg/kg/day (maximum 20 mg/day) administered twice a day (BID) in equally divided doses.	Cohort 2: Matching Placebo Matching placebo administered twice a day (BID) in equally divided doses.
Overall Study STARTED	43	44
Overall Study COMPLETED	36	41
Overall Study NOT COMPLETED	7	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A 2-Part Study to Investigate the Dose-Ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children ≥ 2 Years Old and Young Adults With Dravet Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 2: ZX008 0.5 mg/kg/Day n=43 Participants ZX008 0.5 mg/kg/day (maximum 20 mg/day) dose administered twice a day (BID) in equally divided doses.	Cohort 2: Matching Placebo n=44 Participants Matching placebo administered twice a day (BID) in equally divided doses.	Total n=87 Participants Total of all reporting groups
Age, Continuous Cohort 2	8.8 years STANDARD_DEVIATION 4.56 • n=99 Participants	9.4 years STANDARD_DEVIATION 5.05 • n=107 Participants	9.1 years STANDARD_DEVIATION 4.80 • n=206 Participants
Sex: Female, Male Cohort 2 · Female	20 Participants n=99 Participants	17 Participants n=107 Participants	37 Participants n=206 Participants
Sex: Female, Male Cohort 2 · Male	23 Participants n=99 Participants	27 Participants n=107 Participants	50 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=99 Participants	7 Participants n=107 Participants	10 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=99 Participants	22 Participants n=107 Participants	47 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=99 Participants	15 Participants n=107 Participants	30 Participants n=206 Participants
Race (NIH/OMB) Cohort 2 · American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Cohort 2 · Asian	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Cohort 2 · Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Cohort 2 · Black or African American	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Cohort 2 · White	23 Participants n=99 Participants	29 Participants n=107 Participants	52 Participants n=206 Participants
Race (NIH/OMB) Cohort 2 · More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Cohort 2 · Unknown or Not Reported	17 Participants n=99 Participants	12 Participants n=107 Participants	29 Participants n=206 Participants
Region of Enrollment Netherlands	8 Participants n=99 Participants	2 Participants n=107 Participants	10 Participants n=206 Participants
Region of Enrollment France	13 Participants n=99 Participants	10 Participants n=107 Participants	23 Participants n=206 Participants
Region of Enrollment Canada	4 Participants n=99 Participants	3 Participants n=107 Participants	7 Participants n=206 Participants
Region of Enrollment United States	11 Participants n=99 Participants	11 Participants n=107 Participants	22 Participants n=206 Participants
Region of Enrollment Germany	0 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants
Region of Enrollment Spain	4 Participants n=99 Participants	6 Participants n=107 Participants	10 Participants n=206 Participants
Region of Enrollment United Kingdom	3 Participants n=99 Participants	9 Participants n=107 Participants	12 Participants n=206 Participants

PRIMARY outcome

Timeframe: 15 weeks (combined Titration + Maintenance Period)

Population: Modified intent-to-treat (mITT) Population, defined as all randomized subjects who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Outcome measures

Outcome measures
Measure	Cohort 2: ZX008 0.5 mg/kg/Day n=43 Participants ZX008 0.5 mg/kg/day (maximum 20 mg/day) administered twice a day (BID) in equally divided doses.	Cohort 2: Matching Placebo n=44 Participants Matching placebo administered twice a day (BID) in equally divided doses.
Change in Convulsive Seizure Frequency (CSF) From the Baseline Period (Baseline) to the Combined Titration + Maintenance (T+M) Period	-3.18 Convulsive seizures per 28 days Standard Deviation 44.121	-0.65 Convulsive seizures per 28 days Standard Deviation 8.767

SECONDARY outcome

Timeframe: 15 weeks (combined Titration + Maintenance Period)

Population: Modified intent-to-treat (mITT) Population, defined as all randomized subjects who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Percentage of participants who achieved ≥ a 50% reduction in convulsive seizure frequency from Baseline compared to the combined Titration + Maintenance Periods in the ZX008 0.5 mg/kg/day vs placebo groups.

Outcome measures

Outcome measures
Measure	Cohort 2: ZX008 0.5 mg/kg/Day n=43 Participants ZX008 0.5 mg/kg/day (maximum 20 mg/day) administered twice a day (BID) in equally divided doses.	Cohort 2: Matching Placebo n=44 Participants Matching placebo administered twice a day (BID) in equally divided doses.
Percentage of Participants Who Achieved ≥ a 50% Reduction in Convulsive Seizure Frequency From Baseline to the Combined Titration + Maintenance Period	53.5 Percentage of participants	4.5 Percentage of participants

SECONDARY outcome

Timeframe: 15 weeks (combined Titration + Maintenance Period)

Population: Modified intent-to-treat (mITT) Population, defined as all randomized subjects who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Comparison of the duration of the longest convulsive seizure-free interval (days) during the combined Titration + Maintenance Periods for the ZX008 0.5 mg/kg/day and placebo groups.

Outcome measures

Outcome measures
Measure	Cohort 2: ZX008 0.5 mg/kg/Day n=43 Participants ZX008 0.5 mg/kg/day (maximum 20 mg/day) administered twice a day (BID) in equally divided doses.	Cohort 2: Matching Placebo n=44 Participants Matching placebo administered twice a day (BID) in equally divided doses.
Longest Convulsive Seizure-Free Interval (Days)	22.0 Days Interval 3.0 to 105.0	13.0 Days Interval 1.0 to 40.0

Adverse Events

Cohort 2: ZX008 0.5 mg/kg/Day

Serious events: 6 serious events

Other events: 42 other events

Deaths: 0 deaths

Cohort 2: Matching Placebo

Serious events: 7 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 2: ZX008 0.5 mg/kg/Day n=43 participants at risk ZX008 0.5 mg/kg/day (maximum 20 mg/day) dose administered twice a day (BID) in equally divided doses.	Cohort 2: Matching Placebo n=44 participants at risk Matching placebo administered twice a day (BID) in equally divided doses.
Gastrointestinal disorders Abdominal pain	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
General disorders Pyrexia	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Infections and infestations Gastroenteritis viral	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Infections and infestations Lower respiratory tract infection	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Infections and infestations Pneumonia	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Musculoskeletal and connective tissue disorders Osteochondritis	2.3% 1/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	0.00% 0/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Lethargy	2.3% 1/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	0.00% 0/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Seizure	2.3% 1/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	9.1% 4/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Seizure cluster	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Status epilepticus	7.0% 3/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	0.00% 0/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).

Other adverse events

Additional Information

UCB

Cares

Phone: 001 844 599 2273

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 2: ZX008 0.5 mg/kg/Day n=43 participants at risk ZX008 0.5 mg/kg/day (maximum 20 mg/day) dose administered twice a day (BID) in equally divided doses.	Cohort 2: Matching Placebo n=44 participants at risk Matching placebo administered twice a day (BID) in equally divided doses.
Gastrointestinal disorders Diarrhea	23.3% 10/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	6.8% 3/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
General disorders Fatigue	25.6% 11/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	4.5% 2/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
General disorders Pyrexia	25.6% 11/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	9.1% 4/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Infections and infestations Bronchitis	11.6% 5/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	4.5% 2/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Investigations Blood glucose decreased	14.0% 6/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	4.5% 2/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Metabolism and nutrition disorders Decreased appetite	44.2% 19/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	11.4% 5/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Lethargy	14.0% 6/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	4.5% 2/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Seizure	4.7% 2/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	15.9% 7/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Gastrointestinal disorders Constipation	9.3% 4/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Gastrointestinal disorders Vomiting	4.7% 2/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	6.8% 3/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
General disorders Asthenia	7.0% 3/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	4.5% 2/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Infections and infestations Ear Infection	9.3% 4/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	4.5% 2/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Infections and infestations Nasopharyngitis	16.3% 7/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	34.1% 15/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Infections and infestations Rhinitis	7.0% 3/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Infections and infestations Sinusitis	2.3% 1/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	6.8% 3/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Infections and infestations Upper respiratory tract infection	9.3% 4/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	6.8% 3/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Investigations Blood pressure diastolic increased	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	6.8% 3/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Investigations Blood pressure increased	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	6.8% 3/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Investigations Echocardiogram abnormal	9.3% 4/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	0.00% 0/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Investigations Weight decreased	9.3% 4/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Generalized tonic-clonic seizure	0.00% 0/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	6.8% 3/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Somnolence	7.0% 3/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	6.8% 3/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Status epilepticus	11.6% 5/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	0.00% 0/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Nervous system disorders Tremor	11.6% 5/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	0.00% 0/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Psychiatric disorders Abnormal behavior	9.3% 4/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	2.3% 1/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Psychiatric disorders Irritability	9.3% 4/43 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).	4.5% 2/44 • The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).