Treatment of Infantile Spasms

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2021-003015-26-ES
• Date of registration: 25/10/2021
• Prospective Registration: Yes
• Primary sponsor: Amzell B.V.
• Public title: Treatment of Infantile Spasms
• Scientific title: A Phase 3, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of AMZ002, Compared to Vigabatrin, in the Treatment of Infantile Spasms
• Date of first enrolment: 12/04/2022
• Target sample size: 230
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-003015-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Poland, Spain, United States

Contacts

• Name: Project Management
• Affiliation: Amzell B.V.

• Name: Project Management
• Affiliation: Amzell B.V.

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria
Patients who meet all of the following criteria will be eligible to participate in the study:
1. Patient is male or female and is 2 months to 24 months of age, inclusive;
2. Patient has been diagnosed with IS within 6 weeks prior to Screening. Diagnostic criteria
include both clinical spasms and an electroencephalogram (EEG) pattern consistent with hypsarrhythmia or significant abnormality compatible with IS;
NOTE: If a video EEG is performed at the clinical site within 48 hours prior to the patient’s parent/guardian providing written informed consent, and it meets the criteria, this video EEG
may be used as the screening/baseline EEG for the study.
3. Patient has normal renal function as defined by an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2, calculated as eGFR = 0.413 × (height [cm] / serum creatinine [mg/dL]);
4. Patient’s legally authorized representative (ie, parent or guardian) must provide written informed consent obtained per Institutional Review Board policy and requirements, consisten with the International Council for Harmonisation; and
5. Patient’s parent/guardian is able to understand and willing to comply with study procedures and restrictions.
Are the trial subjects under 18? yes
Number of subjects for this age range: 230
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients who meet any of the following criteria will be excluded from participation in the study:
1. Patient has been diagnosed with tuberous sclerosis;
2. Patient has acute illness considered clinically significant by the Investigator within 30 days prior to Screening;
3. Patient has a diagnosis of recent systemic fungal infection; history of ocular herpes simplex;
history of or current peptic ulcer; uncontrolled hypertension or congestive heart failure; or any other condition that would be significantly impacted by the study drug;
4. Patient has a preplanned surgery or procedure(s) that would interfere with the conduct of the study;
5. Patient has received any prior treatment for IS;
6. Patient has been previously treated with adrenocorticotropic hormone (ACTH),
corticosteroids, or vigabatrin for seizures;
7. Patient has been previously treated with a course of corticosteroids for an indication other than seizures within 30 days prior to Screening;
8. Patient has a known or suspected allergy to ACTH or vigabatrin or any component of AMZ002 or vigabatrin;
9. Patient has used any other investigational drug within 30 days or 5 half-lives prior to the first dose of AMZ002 or vigabatrin (whichever is longer);
10. Patient’s parent/guardian is unable to provide written informed consent and/or to complete the daily diary; or
11. Patient has any other disease, condition, or therapy that, in the opinion of the Investigator, might compromise safety or compliance, preclude the patient from successfully completing the study, or interfere with the interpretation of the results.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Monotherapy for the treatment of infantile spasms (IS) in infants and children 2 months to 24 months of age
MedDRA version: 21.1 Level: PT Classification code 10021750 Term: Infantile spasms System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 21.1 Level: LLT Classification code 10021751 Term: Infantile spasms, with intractable epilepsy System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: LLT Classification code 10021752 Term: Infantile spasms, without mention of intractable epilepsy System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: AMZ002
Product Code: AMZ002
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vigabatrin
CAS Number: 60643-86-9
Current Sponsor code: AMZ002
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5-

Trade Name: Sabril
Product Name: Sabril
Product Code: Vigabatrin
Pharmaceutical Form: Granules for oral solution
INN or Proposed INN: Vigabatrin
CAS Number: 60643-86-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: -Day 14, as indicated by video EEG
-Absence of clinical spasms and resolution of hypsarrhythmia

Main Objective: The primary objective of this study is to evaluate the efficacy of AMZ002 in patients who are 2 months to 24 months of age, inclusive, with newly diagnosed IS, compared to vigabatrin.

Secondary Objective: The secondary objectives of this study are the following:
• To evaluate the safety of AMZ002 in patients who are 2 months to 24 months of age, inclusive, with newly diagnosed IS; and
• To evaluate the pharmacodynamics (PD) of AMZ002 in patients who are 2 months to
24 months of age, inclusive, with newly diagnosed IS.

Primary end point(s): Primary Efficacy Endpoints
The co-primary efficacy endpoints are the following:
• Proportion of patients with absence of clinical spasms at Day 14, as indicated by video EEG; and
• Proportion of patients with resolution of hypsarrhythmia or significant abnormality compatible with IS at Day 14, as indicated by video EEG.
Absence of clinical spasms and resolution of hypsarrhythmia or significant abnormality compatible with IS will be determined by an independent, blinded, and central EEG reader.

Secondary Outcome(s)

Secondary end point(s): Exploratory Efficacy Endpoints
The exploratory efficacy endpoints are the following, for patients randomized to the vigabatrin group who are non-responders at Day 14 and then choose to switch to AMZ002 treatment:
• Proportion of patients with absence of clinical spasms after 14 days of AMZ002 treatment, as indicated by the parent/guardian diary; and
• Proportion of patients with resolution of hypsarrhythmia or significant abnormality compatible with IS after 14 days of AMZ002 treatment, as indicated by video EEG.

Timepoint(s) of evaluation of this end point: -patients randomized to the vigabatrin group who are non-responders at Day 14
-Proportion of patients with absence of clinical spasms after 14 days of AMZ002 treatment
- Proportion of patients with resolution of hypsarrhythmia or significant abnormality compatible with IS after 14 days of AMZ002 treatment

Secondary ID(s)

AMZ002-002

Source(s) of Monetary Support

Amzell B.V.

Ethics review

Status: Approved
Approval date: 15/12/2021
Contact: