Infantile Spasms
Conditions
Keywords
GWP42003-P, Cannabidiol
Brief summary
This trial consists of 3 parts: a pilot safety phase, a pivotal randomized controlled phase, and an open-label extension phase. The pilot phase only will be described in this record. 2 cohorts of 5 participants will be enrolled sequentially. All participants will receive GWP42003-P.
Interventions
DRUGGWP42003-P
Clear, colorless to yellow solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label
Eligibility
Sex/Gender
ALL
Age
1 Months to 24 Months
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participant is aged 6- 24 months (inclusive) in the first cohort or aged 1-24 months (inclusive) in the second cohort, at the time of consent. * Participant is diagnosed with IS and has failed to respond adequately following treatment with 1 or more approved IS therapies. * To be considered hypsarrhythmia, as defined for use in the study, the electroencephalography (EEG) background must be slowed and have multifocal spikes. In addition, it must be either high voltage (above 300 µV) or have electrodecrement/discontinuity. Key
Exclusion criteria
* Participant is currently taking or has taken clobazam or any mammalian target of rapamycin (mTOR) inhibitor within the 2 weeks prior to the screening visit. * Participant has a QT interval, corrected for heart rate with Bazett's formula (QTcB), of 460 msec or greater on ECG. * Participant's caregiver is currently giving or has given recreational or medicinal cannabis, or synthetic cannabinoid-based medications, within the 1 month prior to the screening visit. * Participant's caregiver is unwilling to abstain from giving the participant (including the participant's mother abstaining themselves, if breastfeeding)recreational or medicinal cannabis, or synthetic cannabinoid-based medications (other than the study drug) during the trial. * Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the study drug, such as sesame oil. * Participant has significantly impaired hepatic function at the screening visit. * Participant has received an investigational medicinal product as part of a clinical trial within a minimum of 5 half-lives prior to the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Severe Treatment-emergent Adverse Events (TEAEs) | From signing of informed consent up to Day 15 | TEAEs are defined as all adverse events not present prior to the first investigational medicinal product (IMP) or placebo administration or any event already present that worsened in severity or frequency following IMP. |
| Number of Participants With Any Low or High Hematology Laboratory Parameter Value | Day 4 and Day 15 | — |
| Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value | Day 4 and Day 15 | — |
| Number of Participant With Any Clinically Relevant Urinalysis Parameter Value | Day 4 and Day 15 | Clinical relevance was determined by the investigator. |
| Number of Participants With Clinically Significant Electrocardiogram Findings | From signing of informed consent up to Day 15 | Clinical significance was determined by the investigator. |
| Number of Participants With Clinically Significant Physical Examination Findings | From signing of informed consent up to Day 15 | Clinical significance was determined by the investigator. |
| Number of Participants With Clinically Significant Vital Sign Findings | From signing of informed consent up to Day 15 | Clinical significance was determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Time to Cessation of Spasms | Day 1 to start of Open-label Extension (OLE) Phase | Analysis could not be conducted for this outcome measure because the study met No Go Criteria. The Pilot Phase concluded after 9 participants completed treatment and demonstrated continued hypsarrhythmia and spasms on follow-up VEEG. The Pivotal Phase was not initiated; however, participants completing the Pilot Phase could roll into the Open Label Extension Phase (NCT02954887) for up to 1 year. |
| Number of Responders | Baseline to Day 15 | A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by VEEG for at least 8 hours and up to 24 hours. |
| Physician Global Impression of Change (PGIC) | Day 15 | The PGIC is a single-question assessment completed by the investigator. The question assesses the status of the participant's condition since treatment start. The investigator provided a rating on a 7-point scale from 1 (very much improved) to 7 (very much worse). |
| Caregiver Clinical Global Impression of Change (CGIC) | Day 15 | The CGIC is a single-question assessment completed by the caregiver. The question assessed the status of the participant's condition since treatment start. The caregiver provided a rating on a 7-point scale from 1 (very much improved) to 7 (very much worse). |
| Percentage of Responders | Baseline to Day 15 | A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by VEEG for at least 8 hours and up to 24 hours. |
| Number of Participants Free of Clinical Spasms | Day 15 | Clinical spasms were determined by video-electroencephalography (VEEG) for at least 8 hours and up to 24 hours. |
| Percentage of Participants Free of Clinical Spasms | Day 15 | Clinical spasms were determined by VEEG for at least 8 hours and up to 24 hours. |
| Number of Participants With Resolution of Hypsarrhythmia | Day 15 | Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours. |
| Percentage of Participants With Resolution of Hypsarrhythmia | Day 15 | Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours. |
| Number of Participants Experiencing Spasms and Seizures by Subtype | Day 4 and Day 15 | Caregivers recorded the participant's spasms and seizures by category in a daily diary. Subtypes of spasms and seizures included: clonic, tonic-clonic, myoclonic, focal, and absence. |
Countries
Poland, United States
Participant flow
Recruitment details
Participants were screened to assess their eligibility to enter the trial within 7 days prior to the first dose administration.
Participants by arm
| Arm | Count |
|---|---|
| GWP42003-P OS Participants received GWP42003-P oral solution (OS) for 14 days. Starting on Day 1 and over the course of 4 days, participants titrated up to a tolerable dose, not to exceed the target dose of 40 mg/kg/day of GWP42003-P. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | GWP42003-P OS |
|---|---|
| Age, Continuous | 12.2 years STANDARD_DEVIATION 5.56 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 5 / 9 |
| serious Total, serious adverse events | 1 / 9 |
Outcome results
Primary
Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value
Time frame: Day 4 and Day 15
Population: Safety Analysis Set. Only participants with evaluable data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GWP42003-P OS | Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value | Day 4, Low | 7 Participants |
| GWP42003-P OS | Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value | Day 4, High | 5 Participants |
| GWP42003-P OS | Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value | Day 15, Low | 5 Participants |
| GWP42003-P OS | Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value | Day 15, High | 7 Participants |
Primary
Number of Participants With Any Low or High Hematology Laboratory Parameter Value
Time frame: Day 4 and Day 15
Population: Safety Analysis Set. Only participants with evaluable data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GWP42003-P OS | Number of Participants With Any Low or High Hematology Laboratory Parameter Value | Day 4, High | 4 Participants |
| GWP42003-P OS | Number of Participants With Any Low or High Hematology Laboratory Parameter Value | Day 15, Low | 1 Participants |
| GWP42003-P OS | Number of Participants With Any Low or High Hematology Laboratory Parameter Value | Day 15, High | 3 Participants |
| GWP42003-P OS | Number of Participants With Any Low or High Hematology Laboratory Parameter Value | Day 4, Low | 4 Participants |
Primary
Number of Participants With Clinically Significant Electrocardiogram Findings
Clinical significance was determined by the investigator.
Time frame: From signing of informed consent up to Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GWP42003-P OS | Number of Participants With Clinically Significant Electrocardiogram Findings | 0 Participants |
Primary
Number of Participants With Clinically Significant Physical Examination Findings
Clinical significance was determined by the investigator.
Time frame: From signing of informed consent up to Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GWP42003-P OS | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
Primary
Number of Participants With Clinically Significant Vital Sign Findings
Clinical significance was determined by the investigator.
Time frame: From signing of informed consent up to Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GWP42003-P OS | Number of Participants With Clinically Significant Vital Sign Findings | 0 Participants |
Primary
Number of Participants With Severe Treatment-emergent Adverse Events (TEAEs)
TEAEs are defined as all adverse events not present prior to the first investigational medicinal product (IMP) or placebo administration or any event already present that worsened in severity or frequency following IMP.
Time frame: From signing of informed consent up to Day 15
Population: Safety Analysis Set: all participants who received at least 1 dose of GWP42003-P
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GWP42003-P OS | Number of Participants With Severe Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
Primary
Number of Participant With Any Clinically Relevant Urinalysis Parameter Value
Clinical relevance was determined by the investigator.
Time frame: Day 4 and Day 15
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GWP42003-P OS | Number of Participant With Any Clinically Relevant Urinalysis Parameter Value | Day 15 | 0 Participants |
| GWP42003-P OS | Number of Participant With Any Clinically Relevant Urinalysis Parameter Value | Day 4 | 0 Participants |
Secondary
Average Time to Cessation of Spasms
Analysis could not be conducted for this outcome measure because the study met No Go Criteria. The Pilot Phase concluded after 9 participants completed treatment and demonstrated continued hypsarrhythmia and spasms on follow-up VEEG. The Pivotal Phase was not initiated; however, participants completing the Pilot Phase could roll into the Open Label Extension Phase (NCT02954887) for up to 1 year.
Time frame: Day 1 to start of Open-label Extension (OLE) Phase
Population: Safety Analysis Set
Secondary
Caregiver Clinical Global Impression of Change (CGIC)
The CGIC is a single-question assessment completed by the caregiver. The question assessed the status of the participant's condition since treatment start. The caregiver provided a rating on a 7-point scale from 1 (very much improved) to 7 (very much worse).
Time frame: Day 15
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GWP42003-P OS | Caregiver Clinical Global Impression of Change (CGIC) | Very Much Improved | 1 participants |
| GWP42003-P OS | Caregiver Clinical Global Impression of Change (CGIC) | Much Improved | 0 participants |
| GWP42003-P OS | Caregiver Clinical Global Impression of Change (CGIC) | Slightly Improved | 7 participants |
| GWP42003-P OS | Caregiver Clinical Global Impression of Change (CGIC) | No Change | 1 participants |
| GWP42003-P OS | Caregiver Clinical Global Impression of Change (CGIC) | Slightly Worse | 0 participants |
| GWP42003-P OS | Caregiver Clinical Global Impression of Change (CGIC) | Much Worse | 0 participants |
| GWP42003-P OS | Caregiver Clinical Global Impression of Change (CGIC) | Very Much Worse | 0 participants |
| GWP42003-P OS | Caregiver Clinical Global Impression of Change (CGIC) | Not Done | 0 participants |
Secondary
Number of Participants Experiencing Spasms and Seizures by Subtype
Caregivers recorded the participant's spasms and seizures by category in a daily diary. Subtypes of spasms and seizures included: clonic, tonic-clonic, myoclonic, focal, and absence.
Time frame: Day 4 and Day 15
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 4, Atonic | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 4, Myoclonic | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 4, Focal | 1 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 4, Absence | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 4, Not Done | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 15, Clonic | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 15, Tonic-Clonic | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 15, Atonic | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 15, Myoclonic | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 15, Focal | 2 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 15, Absence | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 15, Not Done | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 4, Clonic | 0 Participants |
| GWP42003-P OS | Number of Participants Experiencing Spasms and Seizures by Subtype | Day 4, Tonic-Clonic | 1 Participants |
Secondary
Number of Participants Free of Clinical Spasms
Clinical spasms were determined by video-electroencephalography (VEEG) for at least 8 hours and up to 24 hours.
Time frame: Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GWP42003-P OS | Number of Participants Free of Clinical Spasms | 0 Participants |
Secondary
Number of Participants With Resolution of Hypsarrhythmia
Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours.
Time frame: Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GWP42003-P OS | Number of Participants With Resolution of Hypsarrhythmia | 0 Participants |
Secondary
Number of Responders
A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by VEEG for at least 8 hours and up to 24 hours.
Time frame: Baseline to Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GWP42003-P OS | Number of Responders | 0 responders |
| Cohort 2: GWP42003-P OS | Number of Responders | 0 responders |
Secondary
Percentage of Participants Free of Clinical Spasms
Clinical spasms were determined by VEEG for at least 8 hours and up to 24 hours.
Time frame: Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GWP42003-P OS | Percentage of Participants Free of Clinical Spasms | 0 percentage of participants |
Secondary
Percentage of Participants With Resolution of Hypsarrhythmia
Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours.
Time frame: Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GWP42003-P OS | Percentage of Participants With Resolution of Hypsarrhythmia | 0 percentage of participants |
Secondary
Percentage of Responders
A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by VEEG for at least 8 hours and up to 24 hours.
Time frame: Baseline to Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GWP42003-P OS | Percentage of Responders | 0 responders |
| Cohort 2: GWP42003-P OS | Percentage of Responders | 0 responders |
Secondary
Physician Global Impression of Change (PGIC)
The PGIC is a single-question assessment completed by the investigator. The question assesses the status of the participant's condition since treatment start. The investigator provided a rating on a 7-point scale from 1 (very much improved) to 7 (very much worse).
Time frame: Day 15
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GWP42003-P OS | Physician Global Impression of Change (PGIC) | Very Much Improved | 0 participants |
| GWP42003-P OS | Physician Global Impression of Change (PGIC) | No Change | 3 participants |
| GWP42003-P OS | Physician Global Impression of Change (PGIC) | Slightly Worse | 0 participants |
| GWP42003-P OS | Physician Global Impression of Change (PGIC) | Much Worse | 0 participants |
| GWP42003-P OS | Physician Global Impression of Change (PGIC) | Very Much Worse | 0 participants |
| GWP42003-P OS | Physician Global Impression of Change (PGIC) | Not Done | 0 participants |
| GWP42003-P OS | Physician Global Impression of Change (PGIC) | Much Improved | 1 participants |
| GWP42003-P OS | Physician Global Impression of Change (PGIC) | Slightly Improved | 5 participants |