Spasms, Infantile
Conditions
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
Interventions
20 or 40 mg/kg/day BID
Sponsors
INSYS Therapeutics Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 36 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of Participants Who Are Considered Complete Responders at Day 14 | 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) | Up to Week 64 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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 | 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 | 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: Percentage of Participants With Absence of Infantile Spasms at Day 14 | Day 14 | — |
| 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 | — |
| 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 A: Percentage of Participants With Absence of Hypsarrhythmia at Day 14 | Day 14 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID |
|---|---|
| Age, Continuous | 23.0 Months STANDARD_DEVIATION 7.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 4 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
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.
Time frame: Day 14
Population: Efficacy Analysis Population: included all participants who received study drug for at least 14 days and underwent video EEG on Day 14.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Percentage of Participants Who Are Considered Complete Responders at Day 14 | 14.3 Percentage of participants |
Primary
Part B: Percentage of Participants Experiencing Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), and Serious Adverse Events (SAEs)
Time frame: Up to Week 64
Population: Safety Analysis Population: included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part B: Percentage of Participants Experiencing Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), and Serious Adverse Events (SAEs) | AEs | 44.4 Percentage of participants |
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part B: Percentage of Participants Experiencing Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), and Serious Adverse Events (SAEs) | TEAEs | 33.3 Percentage of participants |
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part B: Percentage of Participants Experiencing Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), and Serious Adverse Events (SAEs) | SAEs | 0.0 Percentage of participants |
Secondary
Part A: Median Reduction in Seizure-burden Comparing Video-EEG at Baseline to Repeat Video-EEG at Day 14
Time frame: Baseline, Day 14
Population: Efficacy Analysis Population: included all participants who received study drug for at least 14 days and underwent video EEG on Day 14.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Median Reduction in Seizure-burden Comparing Video-EEG at Baseline to Repeat Video-EEG at Day 14 | Visit 1(Baseline) | 0.0 Number of spasms |
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Median Reduction in Seizure-burden Comparing Video-EEG at Baseline to Repeat Video-EEG at Day 14 | Visit 3 (Day 14) | 9.0 Number of spasms |
Secondary
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
Time frame: Visit 3 (Day 14), Visit 4 (Week 4), Visit 5 (Week 8), Visit 6 (Week 10), and end of study.
Population: Efficacy Analysis Population: included all participants who received study drug for at least 14 days and underwent video EEG on Day 14.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Parent Impression of Efficacy and Tolerability of Study Drug | Visit 3 (Day 14) | 3.0 Units on a scale | Standard Deviation 1 |
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Parent Impression of Efficacy and Tolerability of Study Drug | Visit 4 (Week 4) | 1.0 Units on a scale | — |
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Parent Impression of Efficacy and Tolerability of Study Drug | Visit 5 (Week 8) | 1.0 Units on a scale | — |
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Parent Impression of Efficacy and Tolerability of Study Drug | Visit 6 (Week 10) | 1.0 Units on a scale | — |
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Parent Impression of Efficacy and Tolerability of Study Drug | Early Discontinuation/ End of Study | 4.0 Units on a scale | — |
Secondary
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.
Time frame: Day 14
Population: Efficacy Analysis Population: included all participants who received study drug for at least 14 days and underwent video EEG on Day 14.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Percentage of Complete Responders With Relapse | 0 Percentage of participants |
Secondary
Part A: Percentage of Participants With Absence of Hypsarrhythmia at Day 14
Time frame: Day 14
Population: Efficacy Analysis Population: included all participants who received study drug for at least 14 days and underwent video EEG on Day 14.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Percentage of Participants With Absence of Hypsarrhythmia at Day 14 | 42.9 Percentage of participants |
Secondary
Part A: Percentage of Participants With Absence of Infantile Spasms at Day 14
Time frame: Day 14
Population: Efficacy Analysis Population: included all participants who received study drug for at least 14 days and underwent video EEG on Day 14.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Percentage of Participants With Absence of Infantile Spasms at Day 14 | 42.9 Percentage of participants |
Secondary
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.
Time frame: Day 14
Population: Efficacy Analysis Population: included all participants who received study drug for at least 14 days and underwent video EEG on Day 14.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Percentage of Participants With a Partial Response to Treatment | 0 Percentage of participants |
Secondary
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.
Time frame: Day 14
Population: Efficacy Analysis Population: included all participants who received study drug for at least 14 days and underwent video EEG on Day 14.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cannabidiol Oral Solution: 20 or 40 mg/kg/Day BID | Part A: Time to Complete Responder Relapse | NA Days |
Secondary
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
Population: Due to concerns of participant confidentiality this outcome measure was not analyzed. Only 1 participant participated in Part B due to study termination.
Secondary
Part B: Median Reduction in Seizure-burden Comparing Seizure Diaries Throughout Part B.
Time frame: Up to Week 64
Population: Due to concerns of participant confidentiality this outcome measure was not analyzed. Only 1 participant participated in Part B due to study termination.
Secondary
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
Population: Due to concerns of participant confidentiality this outcome measure was not analyzed. Only 1 participant participated in Part B due to study termination.
Secondary
Part B: Percentage of Participants Who Have a Relapse of Spasms Based on Video-EEG
Time frame: Up to Week 64
Population: Due to concerns of participant confidentiality this outcome measure was not analyzed. Only 1 participant participated in Part B due to study termination.
Secondary
Part B: Time to Relapse as Confirmed by Video-EEG
Time frame: Up to Week 64
Population: Due to concerns of participant confidentiality this outcome measure was not analyzed. Only 1 participant participated in Part B due to study termination.