Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
- Registration Number
- NCT02954887
- Lead Sponsor
- Jazz Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 9
- Participant is diagnosed with IS and has failed to respond adequately following treatment with 1 or more approved IS therapies.
Key
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description GWP42003-P GWP42003-P 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value Days 19, 29, 43, 71, 127, 211, 295, 379, and 389 Number of Participants With Clinically Significant Vital Sign Findings From signing of informed consent up to Day 389 Clinical significance was determined by the investigator.
Number of Participants With Severe Treatment-emergent Adverse Events (TEAEs) From signing of informed consent up to Day 417 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 Clinically Significant Physical Examination Findings From signing of informed consent up to Day 389 Clinical significance was determined by the investigator.
Number of Participants With Any Low or High Hematology Laboratory Parameter Value Days 19, 29, 43, 71, 127, 211, 295, 379, and 389 Number of Participants With Any Clinically Relevant Urinalysis Parameter Value Days 19, 29, 43, 71, 127, 211, 295, 379, and 389 Clinical relevance was determined by the investigator.
Number of Participants With Clinically Significant Electrocardiogram Findings From signing of informed consent up to Day 389 Clinical significance was determined by the investigator.
- Secondary Outcome Measures
Name Time Method Number of Participants Free of Clinical Spasms Days 29, 43, 127, 211, 295, and 379 Clinical spasms were determined by video-electroencephalography (VEEG) for at least 8 hours and up to 24 hours.
Percentage of Participants With a Resolution of Hypsarrhythmia Days 29, 43, 127, 211, 295, and 379 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 Days 19, 29, 127, 211, 295, and 379 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.
Change From Baseline in Height Baseline (Day 1 of Pilot Study); Days 29, 43, 71, 127, 211, 295, 379, and 389 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.
Number of Participants With a Resolution of Hypsarrhythmia Days 29, 43, 127, 211, 295, and 379 Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours.
Number of Responders Days 29, 43, 127, 211, 295, and 379 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 Participants Free of Clinical Spasms Days 29, 43, 127, 211, 295, and 379 Clinical spasms were determined by VEEG for at least 8 hours and up to 24 hours.
Physician Global Impression of Change (PGIC) Baseline; Days 29, 43, 71, 127, 211, 295, and 379 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.
Percentage of Responders Days 29, 43, 127, 211, 295, and 379 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 Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score Baseline (Day 1 of Pilot Study); Day 211, Day 379 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 Day 16 to Day 379 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.
Caregiver Global Impression of Change (CGIC) Baseline; Days 29, 43, 71, 127, 211, 295, and 379 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.
Change From Baseline in Body Weight. Baseline (Day 1 of Pilot Study); Days 29, 43, 71, 127, 211, 295, 379, and 389 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 Baseline (Day 1 of PIlot Study); Days 29, 43, 71, 127, 211, 295, 379, and 389 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.
Average Time to Cessation of Spasms Day 1 to Day 379 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 Day 16 to Day 379 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 Day 16 to Day 379 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.
Trial Locations
- Locations (7)
Le Bonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
Centrum Medyczne POMOC
🇵🇱Łódź, Poland
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
Valley Health Clinical Research
🇺🇸Winchester, Virginia, United States