Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)

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

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.

Study Overview

• Status: Completed
• Conditions: Infantile Spasms
• Intervention / Treatment: Drug: GWP42003-P

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Gdańsk, Poland
    • Uniwersyteckie Centrum Kliniczne
  • Łódź, Poland
    • Centrum Medyczne POMOC
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Le Bonheur Children's Hospital
  • Virginia
    • Winchester, Virginia, United States, 22601
      • Valley Health Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 8 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: GWP42003-P; Clear, colorless to yellow solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.; Other Names: Cannabidiol; CBD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From signing of informed consent up to Day 417
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 Low or High Biochemistry Laboratory Parameter Value		Days 19, 29, 43, 71, 127, 211, 295, 379, and 389
Number of Participants With Any Clinically Relevant Urinalysis Parameter Value	Clinical relevance was determined by the investigator.	Days 19, 29, 43, 71, 127, 211, 295, 379, and 389
Number of Participants With Clinically Significant Electrocardiogram Findings	Clinical significance was determined by the investigator.	From signing of informed consent up to Day 389
Number of Participants With Clinically Significant Vital Sign Findings	Clinical significance was determined by the investigator.	From signing of informed consent up to Day 389
Number of Participants With Clinically Significant Physical Examination Findings	Clinical significance was determined by the investigator.	From signing of informed consent up to Day 389

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Days 29, 43, 127, 211, 295, and 379
Percentage of Participants Free of Clinical Spasms	Clinical spasms were determined by VEEG for at least 8 hours and up to 24 hours.	Days 29, 43, 127, 211, 295, and 379
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.	Days 29, 43, 127, 211, 295, and 379
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.	Days 29, 43, 127, 211, 295, and 379
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.	Days 19, 29, 127, 211, 295, and 379
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.	Baseline; Days 29, 43, 71, 127, 211, 295, and 379
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.	Baseline; Days 29, 43, 71, 127, 211, 295, and 379
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.	Days 29, 43, 127, 211, 295, and 379
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.	Days 29, 43, 127, 211, 295, and 379
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.	Baseline (Day 1 of Pilot Study); Days 29, 43, 71, 127, 211, 295, 379, and 389
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.	Baseline (Day 1 of Pilot Study); Days 29, 43, 71, 127, 211, 295, 379, and 389
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.	Baseline (Day 1 of PIlot Study); Days 29, 43, 71, 127, 211, 295, 379, and 389
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.	Baseline (Day 1 of Pilot Study); Day 211, Day 379
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.	Day 16 to Day 379
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.	Day 16 to Day 379
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.	Day 1 to Day 379
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.	Day 16 to Day 379

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2017
• Primary Completion (Actual): June 13, 2019
• Study Completion (Actual): June 13, 2019

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 4, 2016

Study Record Updates

• Last Update Posted (Actual): September 2, 2022
• Last Update Submitted That Met QC Criteria: August 31, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: GWP42003-P; Cannabidiol
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Neurologic Manifestations; Neuromuscular Manifestations; Epilepsy; Spasms, Infantile; Spasm; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: GWEP15100 Open-label Extension; 2015-004904-50 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No