Infantile Spasm
Conditions
Keywords
Infantile spasm, Vigabatrin, Cannabidiol oral solution
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.
Interventions
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
DRUGPlacebo
Matching oral solution
DRUGVigabatrin
Powder suspension
Sponsors
Radius Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Months to 24 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Time to Relapse During the Extended Treatment Period | Up to Day 75 | — |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Pre-assignment details
This study was comprised of five periods. The Screening Period lasted up to 14 days, the Initial Treatment period lasted up to 15 days, the Extended Treatment period lasted up to 75 days, followed by a 6-day Taper period and a 30 day Follow up period, with a maximum duration of approximately 140 days.
Participants by arm
| Arm | Count |
|---|---|
| CBD With Vigabatrin Participants received up to 40 mg/kg/day BID of CBD orally with food during the 15-day Initial Treatment Period. Participants also received up to 150 mg/kg/day BID of vigabatrin orally with food. During the Extended Treatment Period, complete responders continued their assigned treatment of vigabatrin plus CBD 40 mg/kg/day up to Day 75. | 0 |
| Placebo With Vigabatrin Participants received a matching placebo to CBD, orally with food during the 15-day Initial Treatment Period. Participants also received up to 150 mg/kg/day BID of vigabatrin orally with food. During the Extended Treatment Period, complete responders continued their assigned treatment of vigabatrin plus matching placebo up to Day 75. | 0 |
| Total | 0 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Percentage of Participants Considered Complete Responders
Complete response is defined as complete resolution of spasms and hypsarrhythmia confirmed by 24-hour video-electroencephalogram (EEG).
Time frame: Up to Day 15
Population: This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Investigator Impression of Efficacy and Tolerability of Study Drug Clinical Global Impression- Global Improvement (CGI-I)
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.
Time frame: Day 15
Population: This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Percentage of Participants With Complete Response During the Initial Treatment Period Who Relapse During the Extended Treatment Period
Relapse during the extended treatment period will be confirmed by video-EEG following parent report of relapse.
Time frame: Up to Day 75
Population: This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Percentage of Participants With Increase in Number of Spasm-Free Days Between Day 1 and Day 15
Increase in spasm-free days will be determined by seizure diary entries.
Time frame: Up to Day 15
Population: This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Percentage of Participants With Resolution of Hypsarrhythmia
Resolution of hypsarrhythmia was assessed by 24-hour video-EEG.
Time frame: Up to Day 15
Population: This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Percentage of Participants With Resolution of Infantile Spasms
Resolution of IS was assessed by 24-hour video-EEG.
Time frame: Up to Day 15
Population: This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Time to Relapse During the Extended Treatment Period
Time frame: Up to Day 75
Population: This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.