Clinical Trial Results:
An open-label adaptive study for the assessment of safety, tolerability, pharmacokinetics, and efficacy of multiple doses of radiprodil in subjects with drug-resistant infantile spasms
|
Summary
|
|
EudraCT number |
2016-002107-26 |
Trial protocol |
GB BE DE BG FR |
Global end of trial date |
02 Oct 2018
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
17 Apr 2019
|
First version publication date |
17 Apr 2019
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
EP0078
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02829827 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
UCB Biopharma SPRL
|
||
Sponsor organisation address |
Allée de la Recherche 60, Brussels, Belgium, 1070
|
||
Public contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
|
||
Scientific contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
10 Jan 2019
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
02 Oct 2018
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Part A:
To
- Evaluate the safety and tolerability of radiprodil in subjects with drug-resistant infantile spasms
- Evaluate the pharmacokinetics of radiprodil in subjects with drug-resistant infantile spasms
- Evaluate the efficacy of radiprodil in abolishing clinical spasms in subjects with drug-resistant infantile spasms
Part B:
To
- Evaluate the efficacy of radiprodil in abolishing clinical spasms and achieving the resolution of hypsarrhythmia (or other disordered interictal electroencephalogram (EEG) patterns consistent with the diagnosis) in subjects with drug-resistant infantile spasms
- Evaluate the safety and tolerability of radiprodil in subjects with drug-resistant infantile spasms
Part C:
To
- Investigate the safety and tolerability of radiprodil over repeated treatment cycles
- Investigate the efficacy of radiprodil in infants who have responded to 2 treatment cycles in Part A but experienced a relapse within 3 days of treatment cessation
|
||
Protection of trial subjects |
During the conduct of the study all subjects were closely monitored.
|
||
Background therapy |
Background therapy as permitted in the protocol. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
04 Dec 2017
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
12 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
France: 3
|
||
Worldwide total number of subjects |
3
|
||
EEA total number of subjects |
3
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
3
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||
|
Recruitment
|
|||||||||||
Recruitment details |
The study started to enroll patients in December 2017 and was terminated in October 2018. | ||||||||||
|
Pre-assignment
|
|||||||||||
Screening details |
The Participant Flow refers to the Safety Set (SS). | ||||||||||
|
Period 1
|
|||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||
Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
|
||||||||||
Blinding used |
Not blinded | ||||||||||
|
Arms
|
|||||||||||
|
Arm title
|
Radiprodil | ||||||||||
Arm description |
Each subject entered an individualized dose titration schedule. The titration included 3 dose levels of radiprodil: low, medium, high, given bid for 3 days (Day 1L to Day 3L, Day 1M to Day 3M, Day 1H to Day 3H). Titration from L dose to M dose was decided by the investigator: if spasms continued with no safety/tolerability issues, the dose was increased to M, if spasms were absent for 24h, the L dose remained the Maintenance dose. Dose titration from M to H and/or Maintenance of M dose was decided by the investigator, following the same procedure. The Maintenance period occurred over a period of 14 Days (Day14Maint) if spasm continued on Day 3H and there were no safety/tolerability issues, or 28 days (Day28Maint) if spasms were absent for 24h. If spasms were still present at Day14Maint, radiprodil tapering took place: from L dose to L dose 1 per day for 3 days, from M dose to L dose, 3 days bid, from H dose to M dose, 3 days bid. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Radiprodil
|
||||||||||
Investigational medicinal product code |
UCB3491
|
||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Granules for oral suspension
|
||||||||||
Routes of administration |
Oral use
|
||||||||||
Dosage and administration details |
Subjects were administered 3 dose levels (low, medium, high) of radiprodil, given bid for 3 days, as follows: low dose from Day1L to Day 3L, with maintenance of low dose if spasms were absent 24h, or titration to middle dose, if spasms continued. Middle dose from Day1M to Day3M, with maintenance of middle dose if spasms were absent 24 hours, or titration to high dose if spasms continued. High dose from Day1H to day3H, with maintenance of high dose if spasms were absent 24h, for 28Days (28Maint), or tapering if spasms were still present over a period of 14 days (Day14Maint). Radiprodil tapering was done from low dose to low dose, once a day for 3 days; middle dose to low dose, 3 days bid and high dose to middle dose, 3 days bid.
|
||||||||||
|
|||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Radiprodil
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Each subject entered an individualized dose titration schedule. The titration included 3 dose levels of radiprodil: low, medium, high, given bid for 3 days (Day 1L to Day 3L, Day 1M to Day 3M, Day 1H to Day 3H). Titration from L dose to M dose was decided by the investigator: if spasms continued with no safety/tolerability issues, the dose was increased to M, if spasms were absent for 24h, the L dose remained the Maintenance dose. Dose titration from M to H and/or Maintenance of M dose was decided by the investigator, following the same procedure. The Maintenance period occurred over a period of 14 Days (Day14Maint) if spasm continued on Day 3H and there were no safety/tolerability issues, or 28 days (Day28Maint) if spasms were absent for 24h. If spasms were still present at Day14Maint, radiprodil tapering took place: from L dose to L dose 1 per day for 3 days, from M dose to L dose, 3 days bid, from H dose to M dose, 3 days bid. | |||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Radiprodil (SS)
|
|||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Each subject entered an individualized dose titration schedule. The titration included 3 dose levels of radiprodil: low, medium, high, given bid for 3 days (Day 1L to Day 3L, Day 1M to Day 3M, Day 1H to Day 3H). Titration from L dose to M dose was decided by the investigator: if spasms continued with no safety/tolerability issues, the dose was increased to M, if spasms were absent for 24h, the L dose remained the Maintenance dose.
Dose titration from M to H and/or Maintenance of M dose was decided by the investigator, following the same procedure.
The Maintenance period occurred over a period of 14 Days (Day14Maint) if spasm continued on Day 3H and there were no safety/tolerability issues, or 28 days (Day28Maint) if spasms were absent for 24h. If spasms were still present at Day14Maint, radiprodil tapering took place: from L dose to L dose 1 per day for 3 days, from M dose to L dose, 3 days bid, from H dose to M dose, 3 days bid forming the Safety Set (SS).
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Radiprodil
|
||
Reporting group description |
Each subject entered an individualized dose titration schedule. The titration included 3 dose levels of radiprodil: low, medium, high, given bid for 3 days (Day 1L to Day 3L, Day 1M to Day 3M, Day 1H to Day 3H). Titration from L dose to M dose was decided by the investigator: if spasms continued with no safety/tolerability issues, the dose was increased to M, if spasms were absent for 24h, the L dose remained the Maintenance dose. Dose titration from M to H and/or Maintenance of M dose was decided by the investigator, following the same procedure. The Maintenance period occurred over a period of 14 Days (Day14Maint) if spasm continued on Day 3H and there were no safety/tolerability issues, or 28 days (Day28Maint) if spasms were absent for 24h. If spasms were still present at Day14Maint, radiprodil tapering took place: from L dose to L dose 1 per day for 3 days, from M dose to L dose, 3 days bid, from H dose to M dose, 3 days bid. | ||
Subject analysis set title |
Radiprodil (SS)
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Each subject entered an individualized dose titration schedule. The titration included 3 dose levels of radiprodil: low, medium, high, given bid for 3 days (Day 1L to Day 3L, Day 1M to Day 3M, Day 1H to Day 3H). Titration from L dose to M dose was decided by the investigator: if spasms continued with no safety/tolerability issues, the dose was increased to M, if spasms were absent for 24h, the L dose remained the Maintenance dose.
Dose titration from M to H and/or Maintenance of M dose was decided by the investigator, following the same procedure.
The Maintenance period occurred over a period of 14 Days (Day14Maint) if spasm continued on Day 3H and there were no safety/tolerability issues, or 28 days (Day28Maint) if spasms were absent for 24h. If spasms were still present at Day14Maint, radiprodil tapering took place: from L dose to L dose 1 per day for 3 days, from M dose to L dose, 3 days bid, from H dose to M dose, 3 days bid forming the Safety Set (SS).
|
||
|
|||||||||
End point title |
Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil [1] | ||||||||
End point description |
Clinical response was defined as no spasms on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part A.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Day 14, counting from the first day of radiprodil at maintenance dose
|
||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||
End point title |
Plasma concentration of radiprodil at Day 1 [2] | ||||||||||||||||||||||||||||||||
End point description |
This is a primary variable for Part A.
Radiprodil plasma concentration was expressed in nanograms per millilitre (ng/mL).
Concentrations that were Below the lower Limit of Quantification (BLQ) (1ng/mL) were imputed with half of the Lower Limit of Quatification (LLOQ) for the purpose of calculating descriptive statistics.
Note: 9999 is a placeholder value as the radiprodil plasma concentration was not analysed for one subject at Day 1.
|
||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||
End point timeframe |
PK samples were collected at baseline, any time from Day -14/Day -1 prior dosing and 3h, 4h, 5h, 12h post 1st dose on Day 1 of radiprodil low dose.
|
||||||||||||||||||||||||||||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
|||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
|
|||||||||||||||
End point title |
Area Under the concentration time-Curve (AUC) generated from a population - Pharmacokinetic model [3] | ||||||||||||||
End point description |
This is a primary variable for Part A.
Sampling for pharmacokinetic (PK) analyses was done using the Mitra microsampling technique.
Note: AUC results are from Day 2 low dose, since not all subjects had usable data from Day 1
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
PK samples were collected at baseline, any time from Day -14/Day -1 prior dosing and 3h, 4h, 5h, 12h post 1st dose on Day 1 of radiprodil low dose, mid dose and high dose. Samples were taken at same timepoints after 1st radiprodil low dose on Day 2.
|
||||||||||||||
| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
|||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Maximum plasma concentration (Cmax) generated from a population - Pharmacokinetic model [4] | ||||||||||||||
End point description |
This is a primary variable for Part A.
Sampling for pharmacokinetic (PK) analyses was done using the Mitra microsampling technique.
Note: Cmax results are from Day 2 low dose, since not all subjects had usable data from Day 1.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
PK samples were collected at baseline, any time from Day -14/Day -1 prior dosing and 3h, 4h, 5h, 12h post 1st dose on Day 1 of radiprodil low dose, mid dose and high dose. Samples were taken at same timepoints after 1st radiprodil low dose on Day 2.
|
||||||||||||||
| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
|||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Apparent terminal half-life (t 1/2) generated from a population - Pharmacokinetic model [5] | ||||||||||||||
End point description |
This is a primary variable for Part A.
Sampling for pharmacokinetic (PK) analyses was done using the Mitra microsampling technique.
Note: t 1/2 results are from Day 2 low dose, since not all subjects had usable data from Day 1.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
PK samples were collected at baseline, any time from Day -14/Day -1 prior dosing and 3h, 4h, 5h, 12h post 1st dose on Day 1 of radiprodil low dose, mid dose and high dose. Samples were taken at same timepoints after 1st radiprodil low dose on Day 2.
|
||||||||||||||
| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
|||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||
End point title |
Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil [6] | ||||||||
End point description |
Electro-clinical response was defined as no spasms and resolution of hypsarrhythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part B.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Day 14, counting from the first day of radiprodil at maintenance dose
|
||||||||
| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
|||||||||
|
|||||||||
| Notes [7] - Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||
End point title |
Incidence of Adverse Events (AEs) during the study [8] | ||||||
End point description |
An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. This is a primary variable for all parts.
|
||||||
End point type |
Primary
|
||||||
End point timeframe |
From Baseline (Day -1) to the end of the Post-treatment Period (28 days post last dosing)
|
||||||
| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
|||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||
End point title |
Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil Part A | ||||||||
End point description |
Electro-clinical response was defined as no spasms and resolution of hypsarrhythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is the secondary efficacy variable for Part A.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 14, counting from the first day of radiprodil at maintenance dose
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil Part B | ||||||||
End point description |
Clinical response was defined as no spasms on Day 14 of treatment with the maintenance dose of radiprodil. This is the secondary efficacy variable for Part B.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 14, counting from Day 14 of treatment with the maintenance dose of radiprodil
|
||||||||
|
|||||||||
| Notes [9] - Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Estimates of exposure generated from a population-Pharmacokinetic model | ||||||||
End point description |
This is a secondary variable for Part B.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Pharmacokinetic samples were collected on Day 1 of radiprodil low dose, mid dose and high dose. Additionally, blood samples were taken after 1st dose on Day 2 of radiprodil low dose.
|
||||||||
|
|||||||||
| Notes [10] - Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||
End point title |
Time to cessation of spasms | ||||||||||||||
End point description |
Time to cessation of spasms for clinical responders on Day 14 of treatment with the maintenance dose of radiprodol. This is a secondary efficacy variable for parts A and B.
Note 1: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
Note 2: If spasms have not stopped by Day 14 Maint, then the time to cessation of spasms was considered to be right-censored at Day 14 Maint.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
During the first 14 days of treatment with radiprodil
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||
End point title |
Percentage of responders with clinical relapse | ||||||||
End point description |
The percentage of clinical responders on Day 14 of treatment with the maintenance dose of radiprodil with clinical relapse within 12 months. This is a secondary efficacy variable for parts A and B.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Time to clinical relapse from the day of spasm cessation | ||||||||
End point description |
This is a secondary efficacy variable for parts A and B.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From day of spasms cessation up to 42 months of age
|
||||||||
|
|||||||||
| Notes [11] - No subjects presented clinical relapse. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of electro-clinical responders with electro-clinical relapse | ||||||||
End point description |
The percentage of electro-clinical responders on Day 14 of treatment with the maintenance dose of radiprodil with electro-clinical relapse within 12 months. This is a secondary efficacy variable for parts A and B.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Time to electro-clinical relapse from the day of spasm cessation | ||||||||
End point description |
This is a secondary efficacy variable for parts A and B.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From day of spasms cessation up to 42 months of age
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of subjects with extended electro-clinical response | ||||||||
End point description |
Extended electro-clinical response is defined as no spasms and resolution of hypsarrhythmia for 28 consecutive days from Day 14 of treatment with the maintenance dose of radiprodil. This is a secondary efficacy variable for parts A and B.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of subjects with extended clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil | ||||||||
End point description |
Extended clinical response was defined as no spasms for 28 consecutive days from Day 14 of treatment with the maintenance dose of radiprodil. This is a secondary efficacy variable for part C.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
28 days, counting from Day 14 (inclusive) of maintenance dose
|
||||||||
|
|||||||||
| Notes [12] - Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Number of treatment cycles per subject | ||||||||
End point description |
This is a secondary variable for Part C.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
During Part C (Day -1 to Day 28 of the Maintenance Period)
|
||||||||
|
|||||||||
| Notes [13] - Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of subjects with electro-clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil | ||||||||
End point description |
Electro-clinical response was defined as no spasms and resolution of hypsarrhythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is a secondary efficacy variable for Part C.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 14, counting from the first day of maintenance dose
|
||||||||
|
|||||||||
| Notes [14] - Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Time to clinical relapse from the first day of no witnessed spasms for each treatment cycle | ||||||||
End point description |
This is a secondary efficacy variable for part C.
Note: Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the first day of no witnessed spasms up to 42 months of age
|
||||||||
|
|||||||||
| Notes [15] - Due to insufficient enrollment (n=3), the study was terminated during Part A by the Sponsor. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From Baseline (Day -1) to the end of the Post-treatment Period (28 days post last dosing).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Radiprodil (SS)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Each subject entered an individualized dose titration schedule. The titration included 3 dose levels of radiprodil: low, medium, high, given bid for 3 days (Day 1L to Day 3L, Day 1M to Day 3M, Day 1H to Day 3H). Titration from L dose to M dose was decided by the investigator: if spasms continued with no safety/tolerability issues, the dose was increased to M, if spasms were absent for 24h, the L dose remained the Maintenance dose. Dose titration from M to H and/or Maintenance of M dose was decided by the investigator, following the same procedure. The Maintenance period occurred over a period of 14 Days (Day14Maint) if spasm continued on Day 3H and there were no safety/tolerability issues, or 28 days (Day28Maint) if spasms were absent for 24h. If spasms were still present at Day14Maint, radiprodil tapering took place: from L dose to L dose 1 per day for 3 days, from M dose to L dose, 3 days bid, from H dose to M dose, 3 days bid forming the Safety Set (SS). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
16 Sep 2016 |
Protocol Amendment 1 (16 Sept 2016) was a substantial amendment and included the addition of language to clarify when substantial protocol amendments would be made. In addition, additional dose escalation criteria were added. |
||
24 Feb 2017 |
Protocol Amendment 3 (24 Feb 2017) was a substantial amendment and included clarification of the interpretation of the 4-hour video electroencephalogram (EEG) assessment in Part A and Part B of the study. The protocol was amended to make the independent review of the EEGs in Part A optional, and to clarify the requirement for the primary investigator’s interpretation. Additionally, perampanel was listed as a specific prohibited medication for this study. |
||
05 Jan 2018 |
Protocol Amendment 5 (05 Jan 2018) was a substantial amendment and included amending the inclusion/exclusion criteria so infants could have been enrolled within 6 months of diagnosis in order to increase the ability to recruit with no detrimental effect on the study quality or safety; and removing prior use of non-standard of care (StoC) infantile spasms (IS) treatments as an exclusion criterion but including non-StoC IS treatments as prohibited concomitant medications. The subject referral timeframe for the failure of StoC was modified to allow flexibility, as the previous limit of a maximum of 28 days was considered too restrictive. Additional countries were added for Part A of the study to support recruitment, and additional information was added to clarify a group of subjects in relation to dose titration stopping criteria. |
||
16 Mar 2018 |
Protocol Amendment 6 (16 Mar 2018) was a substantial amendment and allowed individual subjects who had shown a benefit from radiprodil treatment in Part A of the study access to additional treatment cycles by adding study Part C. Access to additional treatment cycles was limited to only those subjects who showed evidence of a direct pharmacological relationship with spasm control in Part A; ie, showed a response, followed by a relapse within 5 half-lives (3 days), and then again a response to a second cycle. Additionally, the subjects must have shown good acute tolerability and safety to both treatment cycles in Part A. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| After reviewing the feasibility and projected completion date of the study, UCB has made the decision to stop the study. | |||
