Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms (GWPCARE7)

• ClinicalTrials.gov Identifier: NCT02953548
• Recruitment Status: Completed
• First Posted: November 2, 2016
• Results First Posted: July 23, 2020
• Last Update Posted: July 23, 2020
• 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 pilot phase only will be described in this record. 2 cohorts of 5 participants will be enrolled sequentially. 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: April 24, 2017
• Actual Primary Completion Date: May 7, 2018
• Actual Study Completion Date: May 7, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: GWP42003-P; Administered orally, titrating to a target dose of 40 mg/kg/day. Participants continue at the target dose, or the highest tolerated dose up to the target dose, for the remainder of the 2-week treatment period.	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 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.
2. Number of Participants With Any Low or High Hematology Laboratory Parameter Value [ Time Frame: Day 4 and Day 15 ]
3. Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value [ Time Frame: Day 4 and Day 15 ]
4. Number of Participant With Any Clinically Relevant Urinalysis Parameter Value [ Time Frame: Day 4 and Day 15 ]
   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 15 ]
   Clinical significance was determined by the investigator.
6. Number of Participants With Clinically Significant Physical Examination Findings [ Time Frame: From signing of informed consent up to Day 15 ]
   Clinical significance was determined by the investigator.
7. Number of Participants With Clinically Significant Vital Sign Findings [ Time Frame: From signing of informed consent up to Day 15 ]
   Clinical significance was determined by the investigator.

Secondary Outcome Measures :

1. Number of Participants Free of Clinical Spasms [ Time Frame: Day 15 ]
   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: Day 15 ]
   Clinical spasms were determined by VEEG for at least 8 hours and up to 24 hours.
3. Number of Participants With Resolution of Hypsarrhythmia [ Time Frame: Day 15 ]
   Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours.
4. Percentage of Participants With Resolution of Hypsarrhythmia [ Time Frame: Day 15 ]
   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: 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.
6. Average Time to Cessation of Spasms [ Time Frame: 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.
7. Caregiver Clinical Global Impression of Change (CGIC) [ Time Frame: 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).
8. Physician Global Impression of Change (PGIC) [ Time Frame: 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).
9. Number of Responders [ Time Frame: 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.
10. Percentage of Responders [ Time Frame: 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.

Eligibility Criteria

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

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.

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, Texas

The Childrens Hospital of San Antonio

San Antonio, Texas, United States, 78207

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: NCT02953548
• Other Study ID Numbers: GWEP15100 Pilot Phase; 2015-004904-50 ( EudraCT Number )
• First Posted: November 2, 2016
• Results First Posted: July 23, 2020
• Last Update Posted: July 23, 2020
• Last Verified: July 2020

• 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