Back to resultsPhase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
Primary Purpose
Infantile Spasms
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
GWP42003-P
Sponsored by
About this trial
This is an interventional treatment trial for Infantile Spasms focused on measuring GWP42003-P, Cannabidiol
Eligibility Criteria
Only participants who completed the pilot or pivotal phases of the trial may proceed to take part in this open-label extension phase of the trial.
Key eligibility criteria for the blinded phase were as follows:
Key Inclusion Criteria:
- Participant is diagnosed with IS and has failed to respond adequately following treatment with 1 or more approved IS therapies.
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.
Sites / Locations
- Arkansas Children's Hospital
- Wake Forest Baptist Medical Center
- Nationwide Children's Hospital
- Le Bonheur Children's Hospital
- Valley Health Clinical Research
- Uniwersyteckie Centrum Kliniczne
- Centrum Medyczne POMOC
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GWP42003-P
Arm Description
Administered orally, up to the target dose recommended by the data safety monitoring committee. Participants continue at the target dose, or the highest tolerated dose up to the target dose, for a total of 12 months' treatment.
Outcomes
Primary Outcome Measures
Number of Participants With Severe Treatment-emergent Adverse Events (TEAEs)
TEAEs were collected in members of the Safety Population, comprised of all participants who received at least 1 dose of GWP42003-P. 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
Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value
Number of Participants With Any Clinically Relevant Urinalysis Parameter Value
Clinical relevance was determined by the investigator.
Number of Participants With Clinically Significant Electrocardiogram Findings
Clinical significance was determined by the investigator.
Number of Participants With Clinically Significant Vital Sign Findings
Clinical significance was determined by the investigator.
Number of Participants With Clinically Significant Physical Examination Findings
Clinical significance was determined by the investigator.
Secondary Outcome Measures
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.
Percentage of Participants Free of Clinical Spasms
Clinical spasms were determined by VEEG for at least 8 hours and up to 24 hours.
Number of Participants With a Resolution of Hypsarrhythmia
Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours.
Percentage of Participants With a Resolution of Hypsarrhythmia
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
Caregivers recorded the participant's spasms and seizures by category in a daily diary. Subtypes of spasms and seizure included, clonic, tonic-clonic, myoclonic, focal, and absence.
Caregiver 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: 1, very much improved; 2, much Improved; 3, slightly improved; 4, no change; 5, slightly worse; 6, much worse; 7, very much worse.
Physician Global Impression of Change (PGIC)
The PGIC is a single-question assessment completed by the investigator. The question assessed the status of the participant's condition since treatment start. The investigator provided a rating on a 7-point scale: 1, very much improved; 2, much Improved; 3, slightly improved; 4, no change; 5, slightly worse; 6, much worse; 7, very much worse.
Number of Responders
A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Test for responders was conducted by VEEG for at least 8 hours and up to 24 hours.
Percentage of Responders
A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Test for responders was conducted by VEEG for at least 8 hours and up to 24 hours.
Change From Baseline in Height
A positive change indicates an increase in the average participant's height. A negative change indicates a decrease in the average participant's height. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Body Weight.
A positive change indicates an increase in the average participant's weight. A negative change indicates a decrease in the average participant's weight. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Head Circumference
A positive change indicates an increase in the average participant's head circumference. A negative change indicates a decrease in the average participant's head circumference. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score
The Vineland-II scores were assessed by the participant's caregiver. Caregivers were asked to score questions in the following categories: the participant's communication, daily living, physical activity, problem behaviors, and social skills and relationships. Scoring was slightly different for each section, but generally ranged from "usually" (2) to "never" (0). The total score is calculated as the sum of standard scores from the domains and converted into the adaptive behavior composite score (ranging from 20 to 160). Higher scores represent greater levels of functioning, and lower scores represent lower levels of functioning. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Number of Participants With Relapse 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 for up to 1 year.
Percentage of Participants With Relapse 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 for up to 1 year.
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 for up to 1 year.
Average Time to Relapse
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 for up to 1 year.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02954887
Brief Title
Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
Official Title
A Randomized, Double-blind, Placebo-controlled Trial to Investigate the Efficacy and Safety of Cannabidiol (CBD; GWP42003-P) in Infants With Infantile Spasms Following an Initial Open-label Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
May 12, 2017 (Actual)
Primary Completion Date
June 13, 2019 (Actual)
Study Completion Date
June 13, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jazz Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This trial consists of 3 parts: a pilot safety phase, a pivotal randomized controlled phase, and an open-label extension phase. The open-label extension phase only will be described in this record. All participants will receive GWP42003-P.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infantile Spasms
Keywords
GWP42003-P, Cannabidiol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
Open-label
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GWP42003-P
Arm Type
Experimental
Arm Description
Administered orally, up to the target dose recommended by the data safety monitoring committee.
Participants continue at the target dose, or the highest tolerated dose up to the target dose, for a total of 12 months' treatment.
Intervention Type
Drug
Intervention Name(s)
GWP42003-P
Other Intervention Name(s)
CBD, Cannabidiol
Intervention Description
Clear, colorless to yellow solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Primary Outcome Measure Information:
Title
Number of Participants With Severe Treatment-emergent Adverse Events (TEAEs)
Description
TEAEs were collected in members of the Safety Population, comprised of all participants who received at least 1 dose of GWP42003-P. 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 417
Title
Number of Participants With Any Low or High Hematology Laboratory Parameter Value
Time Frame
Days 19, 29, 43, 71, 127, 211, 295, 379, and 389
Title
Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value
Time Frame
Days 19, 29, 43, 71, 127, 211, 295, 379, and 389
Title
Number of Participants With Any Clinically Relevant Urinalysis Parameter Value
Description
Clinical relevance was determined by the investigator.
Time Frame
Days 19, 29, 43, 71, 127, 211, 295, 379, and 389
Title
Number of Participants With Clinically Significant Electrocardiogram Findings
Description
Clinical significance was determined by the investigator.
Time Frame
From signing of informed consent up to Day 389
Title
Number of Participants With Clinically Significant Vital Sign Findings
Description
Clinical significance was determined by the investigator.
Time Frame
From signing of informed consent up to Day 389
Title
Number of Participants With Clinically Significant Physical Examination Findings
Description
Clinical significance was determined by the investigator.
Time Frame
From signing of informed consent up to Day 389
Secondary Outcome Measure Information:
Title
Number of Participants Free of Clinical Spasms
Description
Clinical spasms were determined by video-electroencephalography (VEEG) for at least 8 hours and up to 24 hours.
Time Frame
Days 29, 43, 127, 211, 295, and 379
Title
Percentage of Participants Free of Clinical Spasms
Description
Clinical spasms were determined by VEEG for at least 8 hours and up to 24 hours.
Time Frame
Days 29, 43, 127, 211, 295, and 379
Title
Number of Participants With a Resolution of Hypsarrhythmia
Description
Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours.
Time Frame
Days 29, 43, 127, 211, 295, and 379
Title
Percentage of Participants With a Resolution of Hypsarrhythmia
Description
Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours.
Time Frame
Days 29, 43, 127, 211, 295, and 379
Title
Number of Participants Experiencing Spasms and Seizures by Subtype
Description
Caregivers recorded the participant's spasms and seizures by category in a daily diary. Subtypes of spasms and seizure included, clonic, tonic-clonic, myoclonic, focal, and absence.
Time Frame
Days 19, 29, 127, 211, 295, and 379
Title
Caregiver Global Impression of Change (CGIC)
Description
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: 1, very much improved; 2, much Improved; 3, slightly improved; 4, no change; 5, slightly worse; 6, much worse; 7, very much worse.
Time Frame
Baseline; Days 29, 43, 71, 127, 211, 295, and 379
Title
Physician Global Impression of Change (PGIC)
Description
The PGIC is a single-question assessment completed by the investigator. The question assessed the status of the participant's condition since treatment start. The investigator provided a rating on a 7-point scale: 1, very much improved; 2, much Improved; 3, slightly improved; 4, no change; 5, slightly worse; 6, much worse; 7, very much worse.
Time Frame
Baseline; Days 29, 43, 71, 127, 211, 295, and 379
Title
Number of Responders
Description
A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Test for responders was conducted by VEEG for at least 8 hours and up to 24 hours.
Time Frame
Days 29, 43, 127, 211, 295, and 379
Title
Percentage of Responders
Description
A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Test for responders was conducted by VEEG for at least 8 hours and up to 24 hours.
Time Frame
Days 29, 43, 127, 211, 295, and 379
Title
Change From Baseline in Height
Description
A positive change indicates an increase in the average participant's height. A negative change indicates a decrease in the average participant's height. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline (Day 1 of Pilot Study); Days 29, 43, 71, 127, 211, 295, 379, and 389
Title
Change From Baseline in Body Weight.
Description
A positive change indicates an increase in the average participant's weight. A negative change indicates a decrease in the average participant's weight. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline (Day 1 of Pilot Study); Days 29, 43, 71, 127, 211, 295, 379, and 389
Title
Change From Baseline in Head Circumference
Description
A positive change indicates an increase in the average participant's head circumference. A negative change indicates a decrease in the average participant's head circumference. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline (Day 1 of PIlot Study); Days 29, 43, 71, 127, 211, 295, 379, and 389
Title
Change From Baseline in Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score
Description
The Vineland-II scores were assessed by the participant's caregiver. Caregivers were asked to score questions in the following categories: the participant's communication, daily living, physical activity, problem behaviors, and social skills and relationships. Scoring was slightly different for each section, but generally ranged from "usually" (2) to "never" (0). The total score is calculated as the sum of standard scores from the domains and converted into the adaptive behavior composite score (ranging from 20 to 160). Higher scores represent greater levels of functioning, and lower scores represent lower levels of functioning. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline (Day 1 of Pilot Study); Day 211, Day 379
Title
Number of Participants With Relapse of Spasms
Description
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 for up to 1 year.
Time Frame
Day 16 to Day 379
Title
Percentage of Participants With Relapse of Spasms
Description
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 for up to 1 year.
Time Frame
Day 16 to Day 379
Title
Average Time to Cessation of Spasms
Description
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 for up to 1 year.
Time Frame
Day 1 to Day 379
Title
Average Time to Relapse
Description
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 for up to 1 year.
Time Frame
Day 16 to Day 379
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
24 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Only participants who completed the pilot or pivotal phases of the trial may proceed to take part in this open-label extension phase of the trial.
Key eligibility criteria for the blinded phase were as follows:
Key Inclusion Criteria:
Participant is diagnosed with IS and has failed to respond adequately following treatment with 1 or more approved IS therapies.
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.
Facility Information:
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Le Bonheur Children's Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Valley Health Clinical Research
City
Winchester
State/Province
Virginia
ZIP/Postal Code
22601
Country
United States
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdańsk
Country
Poland
Facility Name
Centrum Medyczne POMOC
City
Łódź
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
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