Back to resultsA Phase 2 Study of Radiprodil in Subjects With Drug-resistant Infantile Spasms (IS)
Primary Purpose
Infantile Spasms (IS)
Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Radiprodil
Sponsored by
About this trial
This is an interventional treatment trial for Infantile Spasms (IS) focused on measuring Radiprodil, Infantile spasms, IS, Infantile, Spasms, Epilepsy, Paediatrics, Drug-resistant, West Syndrome, Hypsarrhythmia
Eligibility Criteria
Inclusion Criteria:
Part A and B:
- Subject is male or female between 2 and 14 months of age
- The diagnosis of infantile spasms (IS)
- Subject has drug-resistant IS
Part C:
- Subject participated in EP0078 Part A and received 2 radiprodil treatment cycles
- Subject experienced a relapse of spasms during the down taper or within 5 half-lives (3 days) discontinuation of radiprodil treatment in Cycle 2 of Part A
- Electroencephalogram (EEG) on baseline Part C is compatible with the diagnosis of infantile spasms
Exclusion Criteria:
Part A and B:
- More than 6 months have passed since the diagnosis of Infantile Spasms (IS)
- Current treatment with cannabinoids
- Subject has hematocrit greater than 60
- Subject has any medical condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study
- Subject has a history or current condition predisposing to respiratory dysfunction
- Current treatment with felbamate
- Current treatment with perampanel
- Ketogenic diet
- Clinically significant lab abnormalities
- Clinically significant abnormality on ECG that, in the opinion of the Investigator, increases the safety risks of participating in the study
- Subject has a lethal or potentially lethal condition other than IS, with a significant risk of death before 18 months of age such as non-ketotic hyperglycinemia
- Body weight is below 4 kg
- Known history of severe anaphylactic reaction secondary to medication intake or serious blood dyscrasias
Part C:
- Subject experienced any acute tolerability issues in either treatment cycle in Part A which the investigator and the sponsor medical monitor consider a risk for further participation
- Subject met any withdrawal criteria in Part A
- Subject has experienced any adverse effects or developed any new medical conditions since enrollment in Part A which the investigator considers could significantly increase the safety risks of participating in Part C
Sites / Locations
- Ep0078 401
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Radiprodil
Arm Description
Each subject will enter an individualized dose titration schedule.
Outcomes
Primary Outcome Measures
Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Clinical response is defined as no spasms on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part A.
Estimates of exposure generated from a population-Pharmacokinetic modelling
This is a primary variable for Part A.
Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Electro-clinical response is defined as no spasms and resolution of hypsarrythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part B.
Incidence of Adverse Events (AEs) during the study
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.
Secondary Outcome Measures
Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Electro-clinical response is defined as no spasms and resolution of hypsarrythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is the secondary efficacy variable for Part A.
Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Clinical response is defined as no spasms on Day 14 of treatment with the maintenance dose of radiprodil. This is the secondary efficacy variable for Part B.
Estimates of exposure generated from a population-Pharmacokinetic modelling
This is a secondary variable for Part B.
Time to cessation of spasms
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.
Percentage of responders with clinical relapse
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.
Time to clinical relapse from the day of spasm cessation
This is a secondary efficacy variable for parts A and B.
Percentage of electro-clinical responders with electro-clinical relapse
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.
Time to electro-clinical relapse from the day of spasm cessation
This is a secondary efficacy variable for parts A and B.
Percentage of subjects with extended clinical response
Extended clinical response is 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 parts A and B.
Percentage of subjects with extended electro-clinical response
Extended electro-clinical response is defined as no spasms and resolution of hypsarrythmia 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.
Percentage of subjects with extended clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil
Extended clinical response is 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.
Number of treatment cycles per subject
This is a secondary variable for Part C.
Percentage of subjects with electro-clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil
Electro-clinical response is defined as no spasms and resolution of hypsarrythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is a secondary efficacy variable for Part C.
Time to clinical relapse from the first day of no witnessed spasms for each treatment cycle
This is a secondary efficacy variable for part C.
Full Information
NCT ID
NCT02829827
First Posted
July 8, 2016
Last Updated
September 16, 2019
Sponsor
UCB Biopharma S.P.R.L.
1. Study Identification
Unique Protocol Identification Number
NCT02829827
Brief Title
A Phase 2 Study of Radiprodil in Subjects With Drug-resistant Infantile Spasms (IS)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
After reviewing the feasibility and projected completion date of the study, UCB has made the decision to stop the study
Study Start Date
December 4, 2017 (Actual)
Primary Completion Date
October 2, 2018 (Actual)
Study Completion Date
October 2, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCB Biopharma S.P.R.L.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to evaluate the safety and tolerability, the pharmacokinetics and the efficacy of radiprodil in abolishing clinical spasms in subjects with drug-resistant infantile spasms
Detailed Description
The study is divided into 3 parts:
Part A - exploratory, Part B - confirmatory, Part C - open label extension
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infantile Spasms (IS)
Keywords
Radiprodil, Infantile spasms, IS, Infantile, Spasms, Epilepsy, Paediatrics, Drug-resistant, West Syndrome, Hypsarrhythmia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Radiprodil
Arm Type
Experimental
Arm Description
Each subject will enter an individualized dose titration schedule.
Intervention Type
Drug
Intervention Name(s)
Radiprodil
Intervention Description
Radiprodil at individualized doses.
Primary Outcome Measure Information:
Title
Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Description
Clinical response is defined as no spasms on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part A.
Time Frame
Day 14, counting from the first day of radiprodil at maintenance dose
Title
Estimates of exposure generated from a population-Pharmacokinetic modelling
Description
This is a primary variable for Part A.
Time Frame
Samples will be taken at baseline (time during Day -14 to -1 prior to dosing) and 3, 4, 5 & 12hr after the 1st dose on Day 1 of radiprodil low, mid & high dose. Blood samples will be taken at same timepoints after 1st dose on Day 2 of radiprodil low dose
Title
Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Description
Electro-clinical response is defined as no spasms and resolution of hypsarrythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part B.
Time Frame
Day 14, counting from the first day of radiprodil at maintenance dose
Title
Incidence of Adverse Events (AEs) during the study
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.
Time Frame
From Baseline (Day -1) to the end of the Post-treatment Period (28 days post last dosing)
Secondary Outcome Measure Information:
Title
Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Description
Electro-clinical response is defined as no spasms and resolution of hypsarrythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is the secondary efficacy variable for Part A.
Time Frame
Day 14, counting from the first day of radiprodil at maintenance dose
Title
Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Description
Clinical response is defined as no spasms on Day 14 of treatment with the maintenance dose of radiprodil. This is the secondary efficacy variable for Part B.
Time Frame
Day 14, counting from Day 14 of treatment with the maintenance dose of radiprodil
Title
Estimates of exposure generated from a population-Pharmacokinetic modelling
Description
This is a secondary variable for Part B.
Time Frame
Pharmacokinetic samples will be collected on Day 1 of radiprodil low dose, mid dose and high dose. Additionally, blood samples will be taken after 1st dose on Day 2 of radiprodil low dose.
Title
Time to cessation of spasms
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.
Time Frame
During the first 14 days of treatment with radiprodil
Title
Percentage of responders with clinical relapse
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.
Time Frame
12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil
Title
Time to clinical relapse from the day of spasm cessation
Description
This is a secondary efficacy variable for parts A and B.
Time Frame
From day of spasms cessation up to 42 months of age
Title
Percentage of electro-clinical responders with electro-clinical relapse
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.
Time Frame
12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil
Title
Time to electro-clinical relapse from the day of spasm cessation
Description
This is a secondary efficacy variable for parts A and B.
Time Frame
From day of spasms cessation up to 42 months of age
Title
Percentage of subjects with extended clinical response
Description
Extended clinical response is 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 parts A and B.
Time Frame
28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil
Title
Percentage of subjects with extended electro-clinical response
Description
Extended electro-clinical response is defined as no spasms and resolution of hypsarrythmia 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.
Time Frame
28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil
Title
Percentage of subjects with extended clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil
Description
Extended clinical response is 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.
Time Frame
28 days, counting from Day 14 (inclusive) of maintenance dose
Title
Number of treatment cycles per subject
Description
This is a secondary variable for Part C.
Time Frame
During Part C (Day -1 to Day 28 of the Maintenance Period)
Title
Percentage of subjects with electro-clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil
Description
Electro-clinical response is defined as no spasms and resolution of hypsarrythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is a secondary efficacy variable for Part C.
Time Frame
Day 14, counting from the first day of maintenance dose
Title
Time to clinical relapse from the first day of no witnessed spasms for each treatment cycle
Description
This is a secondary efficacy variable for part C.
Time Frame
From day of no witnessed spasms up to 42 months of age
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Months
Maximum Age & Unit of Time
14 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Part A and B:
Subject is male or female between 2 and 14 months of age
The diagnosis of infantile spasms (IS)
Subject has drug-resistant IS
Part C:
Subject participated in EP0078 Part A and received 2 radiprodil treatment cycles
Subject experienced a relapse of spasms during the down taper or within 5 half-lives (3 days) discontinuation of radiprodil treatment in Cycle 2 of Part A
Electroencephalogram (EEG) on baseline Part C is compatible with the diagnosis of infantile spasms
Exclusion Criteria:
Part A and B:
More than 6 months have passed since the diagnosis of Infantile Spasms (IS)
Current treatment with cannabinoids
Subject has hematocrit greater than 60
Subject has any medical condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study
Subject has a history or current condition predisposing to respiratory dysfunction
Current treatment with felbamate
Current treatment with perampanel
Ketogenic diet
Clinically significant lab abnormalities
Clinically significant abnormality on ECG that, in the opinion of the Investigator, increases the safety risks of participating in the study
Subject has a lethal or potentially lethal condition other than IS, with a significant risk of death before 18 months of age such as non-ketotic hyperglycinemia
Body weight is below 4 kg
Known history of severe anaphylactic reaction secondary to medication intake or serious blood dyscrasias
Part C:
Subject experienced any acute tolerability issues in either treatment cycle in Part A which the investigator and the sponsor medical monitor consider a risk for further participation
Subject met any withdrawal criteria in Part A
Subject has experienced any adverse effects or developed any new medical conditions since enrollment in Part A which the investigator considers could significantly increase the safety risks of participating in Part C
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Cares
Organizational Affiliation
+1 8445992273 (UCB)
Official's Role
Study Director
Facility Information:
Facility Name
Ep0078 401
City
Paris
Country
France
12. IPD Sharing Statement
Learn more about this trial
A Phase 2 Study of Radiprodil in Subjects With Drug-resistant Infantile Spasms (IS)
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