A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms

Phase 3

Terminated

• Conditions: Infantile Spasm
• Interventions: Drug: Cannabidiol Oral Solution; Drug: Placebo; Drug: Vigabatrin

• Registration Number: NCT03421496
• Lead Sponsor: Radius Pharmaceuticals, Inc.

Brief Summary

The primary purpose of this study was to evaluate the efficacy, safety, and tolerability of Cannabidiol Oral Solution (CBD) as adjunctive therapy with vigabatrin as initial therapy, compared to vigabatrin alone in the treatment of infants newly diagnosed with Infantile Spasms (IS).

Detailed Description

This was a randomized, double-blind, placebo-controlled, parallel-group study in which participants were randomized in a 1:1 ratio to 1 of 2 treatment groups. During the Initial Treatment Period, participants received either vigabatrin plus CBD or vigabatrin plus matching placebo and were dosed approximately every 12 hours, with a meal. This study was comprised of five periods: Screening, Initial Treatment, Extended Treatment, Taper, and Follow up Periods, with a maximum duration of approximately 140 days.

Study Timeline

• Study First Submitted: 2018-01-26
• Study First Submitted QC: 2018-02-01
• Study First Posted: 2018-02-05
• Study Start: 2018-09-05
• Primary Completion: 2019-05-29
• Study Completion: 2019-05-29
• Status Verified: 2023-05
• Results First Submitted: 2023-05-11
• Results First Submitted QC: 2023-05-11
• Last Update Submitted: 2023-05-11
• Results First Posted: 2023-06-07
• Last Update Posted: 2023-06-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

1. Parent(s)/caregiver(s) fully comprehends and signs the informed consent form, understands all study procedures, and can communicate satisfactorily with the Investigator and study coordinator, in accordance with applicable laws, regulations, and local requirements.
2. Clinical diagnosis of Infantile Spasms, confirmed by video-EEG (including at least one cluster of electroclinical spasms [≥3 in any 10-minute epoch] and hypsarrythmia) obtained during the Screening Period and read by a central reader.
3. General good health (defined as the absence of any clinically relevant abnormalities as determined by the Investigator) based on physical and neurological examinations, medical history, and clinical laboratory values completed during the Screening Visit).
4. In the opinion of the investigator, the parent(s)/caregiver(s) is (are) willing and able to comply with the study procedures and visit schedules.

Exclusion Criteria

1. Is considered by the investigator, for any reason (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator's Brochure for Cannabidiol Oral Solution) to be an unsuitable candidate to receive the study drug.
2. Known or suspected allergy to cannabidiol.
3. History of an allergic reaction or a known or suspected sensitivity to any substance that is contained in the investigational product formulation.
4. Use of any cannabidiol/cannabis product within 30 days of study entry.
5. Participant is diagnosed or suspected of having tuberous sclerosis.
6. Participant has received treatment with either vigabatrin, ACTH, or high-dose steroids previously.
7. Previous or concomitant therapy with felbamate, clobazam, valproic acid, or the ketogenic diet.
8. Participant currently on any disallowed CYP3A4-related medication (phenytoin, fluvoxamine, carbamazepine, and St. John's Wort).
9. Previously received any investigational drug or device or investigational therapy within 30 days before Screening.
10. Clinically significant abnormal laboratory values, including: liver function tests (LFTs) such as albumin, direct bilirubin, total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≥3 times the upper limit of normal (ULN). The investigator may deem the participant eligible if he or she judges the laboratory values to be not clinically significant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CBD with Vigabatrin	Vigabatrin	Participants received up to 40 milligrams per kilogram per day (mg/kg/day) divided twice daily (BID) of CBD with food. Participants also received up to 150 mg/kg/day BID of vigabatrin with food.
CBD with Vigabatrin	Cannabidiol Oral Solution	Participants received up to 40 milligrams per kilogram per day (mg/kg/day) divided twice daily (BID) of CBD with food. Participants also received up to 150 mg/kg/day BID of vigabatrin with food.
Placebo with Vigabatrin	Placebo	Participants received a matching placebo to CBD with food, and also received up to 150 mg/kg/day BID of vigabatrin with food.
Placebo with Vigabatrin	Vigabatrin	Participants received a matching placebo to CBD with food, and also received up to 150 mg/kg/day BID of vigabatrin with food.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Considered Complete Responders	Up to Day 15	Complete response is defined as complete resolution of spasms and hypsarrhythmia confirmed by 24-hour video-electroencephalogram (EEG).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Resolution of Infantile Spasms	Up to Day 15	Resolution of IS was assessed by 24-hour video-EEG.
Percentage of Participants With Resolution of Hypsarrhythmia	Up to Day 15	Resolution of hypsarrhythmia was assessed by 24-hour video-EEG.
Investigator Impression of Efficacy and Tolerability of Study Drug Clinical Global Impression- Global Improvement (CGI-I)	Day 15	Investigators will use the CGI-I scale, which is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and is rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Higher scores indicated worse condition.
Percentage of Participants With Increase in Number of Spasm-Free Days Between Day 1 and Day 15	Up to Day 15	Increase in spasm-free days will be determined by seizure diary entries.
Percentage of Participants With Complete Response During the Initial Treatment Period Who Relapse During the Extended Treatment Period	Up to Day 75	Relapse during the extended treatment period will be confirmed by video-EEG following parent report of relapse.
Time to Relapse During the Extended Treatment Period	Up to Day 75

Trial Locations

Locations (5)

Nicklaus Children's Hospital; 🇺🇸 Miami, Florida, United States

Beaumont Children's Hospital; 🇺🇸 Royal Oak, Michigan, United States

Akron Children's Hospital; 🇺🇸 Akron, Ohio, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Institute for Research and Innovation | MultiCare Health System; 🇺🇸 Tacoma, Washington, United States