Cannabidiol Oral Solution for Treatment of Refractory Infantile Spasms

• ClinicalTrials.gov Identifier: NCT02551731
• Recruitment Status: Terminated
• First Posted: September 16, 2015
• Results First Posted: September 19, 2018
• Last Update Posted: September 19, 2018
• Sponsor: INSYS Therapeutics Inc
• Information provided by (Responsible Party): INSYS Therapeutics Inc

Tracking Information

• First Submitted Date: September 14, 2015
• First Posted Date: September 16, 2015
• Results First Submitted Date: July 9, 2018
• Results First Posted Date: September 19, 2018
• Last Update Posted Date: September 19, 2018
• Actual Study Start Date: January 27, 2016
• Actual Primary Completion Date: September 6, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 21, 2018)

• Part A: Percentage of Participants Who Are Considered Complete Responders at Day 14 [ Time Frame: 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.
• Part B: Percentage of Participants Experiencing Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 64 ]

Original Primary Outcome Measures (submitted: September 14, 2015)

• Percentage of participants with absence of infantile spasms at Day 14 [ Time Frame: at Day 14 ]
  Infantile spasms are the specific kind of seizure seen in children diagnosed with condition called Infantile Spasm at Day 14.
• Percentage of participants with absence of hypsarrhythmia at Day 14 [ Time Frame: at Day 14 ]
  Electroencephalography (EEG) is the recording of the brain's electrical activity over a period of time, recorded from electrodes placed on the scalp. Video-EEG is a special form of EEG test that permits the study of brainwaves while seizures are occurring. It helps doctors determine the nature of the seizure and how best to treat it. Hypsarrhythmia is an abnormal pattern recognized in the video-EEG of children with infantile spasms.
• Percentage of participants with absence of both infantile spasms and hypsarrythmia at Day 14 (complete response) [ Time Frame: at Day 14 ]
  If there are no more spasms or hypsarrythmia, it is considered a complete response, meaning the drug had the intended effect.

Current Secondary Outcome Measures (submitted: August 21, 2018)

• Part A: Percentage of Participants With Absence of Infantile Spasms at Day 14 [ Time Frame: Day 14 ]
• Part A: Percentage of Participants With Absence of Hypsarrhythmia at Day 14 [ Time Frame: Day 14 ]
• Part A: Median Reduction in Seizure-burden Comparing Video-EEG at Baseline to Repeat Video-EEG at Day 14 [ Time Frame: Baseline, Day 14 ]
• Part A: Parent Impression of Efficacy and Tolerability of Study Drug [ Time Frame: Visit 3 (Day 14), Visit 4 (Week 4), Visit 5 (Week 8), Visit 6 (Week 10), and end of study. ]
  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
• Part A: Percentage of Participants With a Partial Response to Treatment [ Time Frame: Day 14 ]
  Partial response was defined as a substantive change in background EEG or reduction in spasms on video EEG obtained at Day 14.
• Part A: Percentage of Complete Responders With Relapse [ Time Frame: Day 14 ]
  Complete response was defined as complete resolution of spasms and hypsarrythmia (if present at baseline) confirmed by video-EEG at Day 14.
• Part A: Time to Complete Responder Relapse [ Time Frame: Day 14 ]
  Complete response was defined as complete resolution of spasms and hypsarrythmia (if present at baseline) confirmed by video-EEG at 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 [ Time Frame: 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 [ Time Frame: Up to Week 64 ]
• Part B: Median Reduction in Seizure-burden Comparing Seizure Diaries Throughout Part B. [ Time Frame: Up to Week 64 ]
• Part B: Percentage of Participants Who Have a Relapse of Spasms Based on Video-EEG [ Time Frame: Up to Week 64 ]
• Part B: Time to Relapse as Confirmed by Video-EEG [ Time Frame: Up to Week 64 ]

Original Secondary Outcome Measures (submitted: September 14, 2015)

• Median reduction in seizure-burden comparing video-EEG at Pre-Screen to repeat video-EEG at Day 14 [ Time Frame: Baseline, Day 14 ]
  The seizure-burden is the number of minutes that a child is having seizures during an hour in which they are having seizures. This outcome measures the average reduction in the seizure-burden.
• The parent's impression of efficacy and tolerability of study drug [ Time Frame: At Day 14, monthly visits, and end of study ]
  Parent impression of efficacy and tolerability of study drug as measured by a change in Clinical Global Impression of improvement Assessment at Day 14, monthly visits, and end of study
• Percentage of participants with a partial response to treatment [ Time Frame: within 17 Weeks ]
• Percentage of complete responders who relapsed [ Time Frame: within 17 weeks ]
  Relapse will be confirmed by video-EEG following parent report of relapse.
• Mean time in days to relapse of complete responders [ Time Frame: within 17 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cannabidiol Oral Solution for Treatment of Refractory Infantile Spasms
• Official Title: A Phase 2 Study to Assess the Efficacy and Safety of Cannabidiol Oral Solution for the Treatment of Refractory Infantile Spasms

Brief Summary

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.

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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Spasms, Infantile

Intervention

Drug: Cannabidiol Oral Solution

20 or 40 mg/kg/day BID

Study Arms

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.

Intervention: Drug: Cannabidiol Oral Solution

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 1, 2016): 9
• Original Estimated Enrollment (submitted: September 14, 2015): 20
• Actual Study Completion Date: September 6, 2016
• Actual Primary Completion Date: September 6, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 36 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02551731
• Other Study ID Numbers: INS011-15-054
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: INSYS Therapeutics Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: INSYS Therapeutics Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Neha Parikh; INSYS Therapeutics Inc

• PRS Account: INSYS Therapeutics Inc
• Verification Date: August 2018