A Phase 2 Study of Radiprodil in Subjects With Drug-resistant Infantile Spasms (IS)

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

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

Study Overview

• Status: Terminated
• Conditions: Infantile Spasms (IS)
• Intervention / Treatment: Drug: Radiprodil

Detailed Description

The study is divided into 3 parts:

Part A - exploratory, Part B - confirmatory, Part C - open label extension

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Ep0078 401

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiprodil; Each subject will enter an individualized dose titration schedule.	Drug: Radiprodil; Radiprodil at individualized doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 14, counting from the first day of radiprodil at maintenance dose
Estimates of exposure generated from a population-Pharmacokinetic modelling	This is a primary variable for Part A.	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
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.	Day 14, counting from the first day of radiprodil at maintenance dose
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.	From Baseline (Day -1) to the end of the Post-treatment Period (28 days post last dosing)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 14, counting from the first day of radiprodil at maintenance dose
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.	Day 14, counting from Day 14 of treatment with the maintenance dose of radiprodil
Estimates of exposure generated from a population-Pharmacokinetic modelling	This is a secondary variable for Part B.	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.
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.	During the first 14 days of treatment with radiprodil
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.	12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil
Time to clinical relapse from the day of spasm cessation	This is a secondary efficacy variable for parts A and B.	From day of spasms cessation up to 42 months of age
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.	12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil
Time to electro-clinical relapse from the day of spasm cessation	This is a secondary efficacy variable for parts A and B.	From day of spasms cessation up to 42 months of age
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.	28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil
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.	28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil
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.	28 days, counting from Day 14 (inclusive) of maintenance dose
Number of treatment cycles per subject	This is a secondary variable for Part C.	During Part C (Day -1 to Day 28 of the Maintenance Period)
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.	Day 14, counting from the first day of maintenance dose
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.	From day of no witnessed spasms up to 42 months of age

Collaborators and Investigators

• Sponsor: UCB Biopharma S.P.R.L.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2017
• Primary Completion (Actual): October 2, 2018
• Study Completion (Actual): October 2, 2018

Study Registration Dates

• First Submitted: July 8, 2016
• First Submitted That Met QC Criteria: July 11, 2016
• First Posted (Estimate): July 12, 2016

Study Record Updates

• Last Update Posted (Actual): September 17, 2019
• Last Update Submitted That Met QC Criteria: September 16, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Epilepsy; Hypsarrhythmia; West Syndrome; Paediatrics; Radiprodil; Infantile spasms; IS; Infantile; Spasms; Drug-resistant
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Epilepsy; Spasms, Infantile; Spasm; Muscle Cramp
• Other Study ID Numbers: EP0078; 2016-002107-26 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No