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

• ClinicalTrials.gov Identifier: NCT02954887
• Recruitment Status: Completed
• First Posted: November 4, 2016
• Results First Posted: July 23, 2020
• Last Update Posted: September 2, 2022
• Sponsor: Jazz Pharmaceuticals
• Information provided by (Responsible Party): Jazz Pharmaceuticals

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.

Condition or disease	Intervention/treatment	Phase
Infantile Spasms	Drug: GWP42003-P	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Open-label
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 12, 2017
• Actual Primary Completion Date: June 13, 2019
• Actual Study Completion Date: June 13, 2019

Arms and Interventions

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: CBD; Cannabidiol

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 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.
2. 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 ]
3. 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 ]
4. Number of Participants With Any Clinically Relevant Urinalysis Parameter Value [ Time Frame: Days 19, 29, 43, 71, 127, 211, 295, 379, and 389 ]
   Clinical relevance was determined by the investigator.
5. Number of Participants With Clinically Significant Electrocardiogram Findings [ Time Frame: From signing of informed consent up to Day 389 ]
   Clinical significance was determined by the investigator.
6. Number of Participants With Clinically Significant Vital Sign Findings [ Time Frame: From signing of informed consent up to Day 389 ]
   Clinical significance was determined by the investigator.
7. Number of Participants With Clinically Significant Physical Examination Findings [ Time Frame: From signing of informed consent up to Day 389 ]
   Clinical significance was determined by the investigator.

Secondary Outcome Measures :

1. Number of Participants Free of Clinical Spasms [ Time Frame: 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.
2. Percentage of Participants Free of Clinical Spasms [ Time Frame: Days 29, 43, 127, 211, 295, and 379 ]
   Clinical spasms were determined by VEEG for at least 8 hours and up to 24 hours.
3. Number of Participants With a Resolution of Hypsarrhythmia [ Time Frame: 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.
4. Percentage of Participants With a Resolution of Hypsarrhythmia [ Time Frame: 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.
5. Number of Participants Experiencing Spasms and Seizures by Subtype [ Time Frame: 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.
6. Caregiver Global Impression of Change (CGIC) [ Time Frame: 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.
7. Physician Global Impression of Change (PGIC) [ Time Frame: 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.
8. Number of Responders [ Time Frame: 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.
9. Percentage of Responders [ Time Frame: 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.
10. Change From Baseline in Height [ Time Frame: 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.
11. Change From Baseline in Body Weight. [ Time Frame: 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.
12. Change From Baseline in Head Circumference [ Time Frame: 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.
13. Change From Baseline in Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score [ Time Frame: 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.
14. Number of Participants With Relapse of Spasms [ Time Frame: 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.
15. Percentage of Participants With Relapse of Spasms [ Time Frame: 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.
16. Average Time to Cessation of Spasms [ Time Frame: 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.
17. Average Time to Relapse [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 1 Month to 24 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arkansas

Arkansas Children's Hospital

Little Rock, Arkansas, United States, 72202

United States, North Carolina

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

United States, Tennessee

Le Bonheur Children's Hospital

Memphis, Tennessee, United States, 38103

United States, Virginia

Valley Health Clinical Research

Winchester, Virginia, United States, 22601

Poland

Uniwersyteckie Centrum Kliniczne

Gdańsk, Poland

Centrum Medyczne POMOC

Łódź, Poland

Sponsors and Collaborators

Jazz Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Jazz Pharmaceuticals:

Study Protocol  [PDF] September 20, 2016

Statistical Analysis Plan  [PDF] September 25, 2019

More Information

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02954887
• Other Study ID Numbers: GWEP15100 Open-label Extension; 2015-004904-50 ( EudraCT Number )
• First Posted: November 4, 2016
• Results First Posted: July 23, 2020
• Last Update Posted: September 2, 2022
• Last Verified: August 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jazz Pharmaceuticals:

GWP42003-P; Cannabidiol

Additional relevant MeSH terms:

Spasm; Spasms, Infantile; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Epileptic Syndromes; Cannabidiol; Anticonvulsants