Cannabidiol Oral Solution for Treatment of Refractory Infantile Spasms

A Phase 2 Study to Assess the Efficacy and Safety of Cannabidiol Oral Solution for the Treatment of Refractory Infantile Spasms

Infantile Spasms (IS) is a diagnosis described as a fairly rare and terrible form of epilepsy that usually strikes children in the first year of life. There is a great need for safe and effective therapies in the treatment of IS. This need is even more important for infants and toddlers still sick after being treated with medicine that is already available.

This is a multi-center study to evaluate the efficacy and safety of Cannabidiol Oral Solution (CBD) in the treatment of children aged 6 months through 36 months with a diagnosis of infantile spasms who have not responded to first line therapies.

The overall study duration is expected to be 64 weeks for those subjects who respond to CBD treatment. The maximum possible study duration for each patient is approximately 64 weeks, however a subject will be deemed to have completed the study after 58 weeks.

Study Overview

• Status: Terminated
• Conditions: Spasms, Infantile
• Intervention / Treatment: Drug: Cannabidiol Oral Solution

Detailed Description

A protocol amendment in May 2016 created two parts to this trial: Part A (the extended treatment period) and Part B (the safety treatment period), whose objectives are as follows:

Primary Part A: To evaluate the efficacy of Cannabidiol Oral Solution in treating refractory infantile spasms (IS).

Secondary:

Part A:

• To evaluate the safety of Cannabidiol Oral Solution in treating refractory infantile spasms.

Part B:

• To assess the long-term safety of Cannabidiol Oral Solution as an adjunctive treatment for subjects with Infantile Spasms (IS)
• To establish the continued efficacy of Cannabidiol Oral Solution in maintaining seizure control in subjects with IS
• To assess the global status of subjects taking Cannabidiol Oral Solution for an extended period of time determined by various qualitative assessments
• To monitor for changes in plasma levels of Cannabidiol Oral Solution during long-term treatment of subjects with IS

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Mattel Children's Hospital at UCLA
    • San Francisco, California, United States, 94143
      • University of California - San Francisco
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meets protocol-specified criteria for qualification, including infantile spasms
• Parent(s)/caregiver(s) fully comprehend and sign the informed consent form, understand all study procedures, and can communicate satisfactorily with the Investigator and study coordinator.

Exclusion Criteria:

• History or current use of over-the-counter medications, dietary supplements, or drugs outside protocol-specified parameters

• Signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff
  2. the analysis of results

• During the Safety Treatment and Follow-up Periods, subjects are not to receive the following:

  1. any cannabinoids (CBD, Δ9-tetrahydrocannabinol (THC), hemp oil, Realm Oil or marijuana)
  2. any other investigational drug or investigational device

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: Cannabidiol Oral Solution: 20 or 40 mg/kg/day BID; The dose of Cannabidiol Oral Solution will begin at 20 mg/kg/day [10 mg/kg twice per day (BID)], will be adjusted at any time if the investigator feels the safety or well-being of the participant is at risk, and will be titrated up or down according to protocol-stipulated parameters and at the investigator's discretion after Day 14 to enhance efficacy. Dose will not exceed 40 mg/kg/day.

Drug: Cannabidiol Oral Solution; 20 or 40 mg/kg/day BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants Who Are Considered Complete Responders at Day 14	Complete response was defined as complete resolution of spasms and hypsarrythmia (if present at baseline) confirmed by video-electroencephalogram (EEG) at Day 14.	Day 14
Part B: Percentage of Participants Experiencing Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), and Serious Adverse Events (SAEs)		Up to Week 64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants With Absence of Infantile Spasms at Day 14		Day 14
Part A: Percentage of Participants With Absence of Hypsarrhythmia at Day 14		Day 14
Part A: Median Reduction in Seizure-burden Comparing Video-EEG at Baseline to Repeat Video-EEG at Day 14		Baseline, Day 14
Part A: Parent Impression of Efficacy and Tolerability of Study Drug	Parent impression of efficacy and tolerability, as measured by Clinical Global Impression-Global Improvement Scale (CGI-I), was summarized by visit and status of response (Complete/Partial and No Response) at Visit 3 (Day 14), Visit 4 (Week 4), Visit 5 (Week 8), Visit 6 (Week 10), and end of study. The CGI-I was also analyzed in a continuous scale, as follows: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, and 7 = Very much worse	Visit 3 (Day 14), Visit 4 (Week 4), Visit 5 (Week 8), Visit 6 (Week 10), and end of study.
Part A: Percentage of Participants With a Partial Response to Treatment	Partial response was defined as a substantive change in background EEG or reduction in spasms on video EEG obtained at Day 14.	Day 14
Part A: Percentage of Complete Responders With Relapse	Complete response was defined as complete resolution of spasms and hypsarrythmia (if present at baseline) confirmed by video-EEG at Day 14.	Day 14
Part A: Time to Complete Responder Relapse	Complete response was defined as complete resolution of spasms and hypsarrythmia (if present at baseline) confirmed by video-EEG at Day 14.	Day 14
Part B: Parent Impression of Efficacy and Tolerability of Study Drug as Measured by the Change in Clinical Global Impression of Improvement Assessment (CGI-I), Responses at Every Visit Throughout Part B		Up to Week 64
Part B: Investigator Impression of Efficacy and Tolerability of Study Drug as Measured by the Change in CGI-I Responses at Every Visit Throughout Part B		Up to Week 64
Part B: Median Reduction in Seizure-burden Comparing Seizure Diaries Throughout Part B.		Up to Week 64
Part B: Percentage of Participants Who Have a Relapse of Spasms Based on Video-EEG		Up to Week 64
Part B: Time to Relapse as Confirmed by Video-EEG		Up to Week 64

Collaborators and Investigators

• Sponsor: INSYS Therapeutics Inc
• Investigators: Study Director: Neha Parikh, INSYS Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2016
• Primary Completion (Actual): September 6, 2016
• Study Completion (Actual): September 6, 2016

Study Registration Dates

• First Submitted: September 14, 2015
• First Submitted That Met QC Criteria: September 14, 2015
• First Posted (Estimate): September 16, 2015

Study Record Updates

• Last Update Posted (Actual): September 19, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• 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: INS011-15-054

Drug and device information, study documents

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