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

• ClinicalTrials.gov Identifier: NCT02829827
• Recruitment Status: Terminated
• First Posted: July 12, 2016
• Last Update Posted: September 17, 2019
• Sponsor: UCB Biopharma S.P.R.L.
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma S.P.R.L. )

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

Condition or disease	Intervention/treatment	Phase
Infantile Spasms (IS)	Drug: Radiprodil	Phase 2

Detailed Description:

The study is divided into 3 parts:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 4, 2017
• Actual Primary Completion Date: October 2, 2018
• Actual Study Completion Date: October 2, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil [ Time Frame: Day 14, counting from the first day of radiprodil at maintenance dose ]
   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.
2. Estimates of exposure generated from a population-Pharmacokinetic modelling [ 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 ]
   This is a primary variable for Part A.
3. Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil [ Time Frame: Day 14, counting from the first day of radiprodil at maintenance dose ]
   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.
4. Incidence of Adverse Events (AEs) during the study [ Time Frame: From Baseline (Day -1) to the end of the Post-treatment Period (28 days post last dosing) ]
   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 :

1. Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil [ Time Frame: Day 14, counting from the first day of radiprodil at maintenance dose ]
   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.
2. Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil [ Time Frame: Day 14, counting from 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.
3. Estimates of exposure generated from a population-Pharmacokinetic modelling [ 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. ]
   This is a secondary variable for Part B.
4. Time to cessation of spasms [ Time Frame: During the first 14 days of treatment with radiprodil ]
   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.
5. Percentage of responders with clinical relapse [ Time Frame: 12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil ]
   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.
6. Time to clinical relapse from the day of spasm cessation [ Time Frame: From day of spasms cessation up to 42 months of age ]
   This is a secondary efficacy variable for parts A and B.
7. Percentage of electro-clinical responders with electro-clinical relapse [ Time Frame: 12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil ]
   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.
8. Time to electro-clinical relapse from the day of spasm cessation [ Time Frame: From day of spasms cessation up to 42 months of age ]
   This is a secondary efficacy variable for parts A and B.
9. Percentage of subjects with extended clinical response [ Time Frame: 28 days, counting from Day 14 (inclusive) 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 parts A and B.
10. Percentage of subjects with extended electro-clinical response [ Time Frame: 28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil ]
    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.
11. Percentage of subjects with extended clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil [ Time Frame: 28 days, counting from Day 14 (inclusive) of maintenance dose ]
    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.
12. Number of treatment cycles per subject [ Time Frame: During Part C (Day -1 to Day 28 of the Maintenance Period) ]
    This is a secondary variable for Part C.
13. Percentage of subjects with electro-clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil [ Time Frame: Day 14, counting from the first day of maintenance dose ]
    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.
14. Time to clinical relapse from the first day of no witnessed spasms for each treatment cycle [ Time Frame: From day of no witnessed spasms up to 42 months of age ]
    This is a secondary efficacy variable for part C.

Eligibility Criteria

• Ages Eligible for Study: 2 Months to 14 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

France

Ep0078 401

Paris, France

Sponsors and Collaborators

UCB Biopharma S.P.R.L.

Investigators

• Study Director: UCB Cares; +1 8445992273 (UCB)

More Information

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT02829827
• Other Study ID Numbers: EP0078; 2016-002107-26 ( EudraCT Number )
• First Posted: July 12, 2016
• Last Update Posted: September 17, 2019
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):

Radiprodil; Infantile spasms; IS; Infantile; Spasms; Epilepsy; Paediatrics; Drug-resistant; West Syndrome; Hypsarrhythmia

Additional relevant MeSH terms:

Muscle Cramp; Spasm; Spasms, Infantile; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Epileptic Syndromes