A Study to Evaluate Safety and Efficacy of AMZ002 Treatment, Compared With Vigabatrin in Participants With Infantile Spasms

A Phase 3, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of AMZ002, Compared to Vigabatrin, in the Treatment of Infantile Spasms

The main purpose of this study is to evaluate the efficacy of AMZ002 compared to Vigabatrin in participants with newly diagnosed infantile spasms (IS).

Study Overview

• Status: Withdrawn
• Conditions: Spasms, Infantile
• Intervention / Treatment: Drug: AMZ002 injectable solution, 0.5mg/mL; Drug: Vigabatrin, oral

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Italiano de Buenos Aires
  • Buenos Aires, Argentina
    • Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia
  • Buenos Aires, Argentina
    • Paediatric Hospital Dr. Juan P. Garrahan
• France
  • Bordeaux, France, 33076
    • Chu Bordeaux - Hôpital Des Enfants
  • Bron, France, 69500
    • HFME-Hospices Civils de Lyon
  • Lille, France
    • Hopital Roger Salengro - CHU de Lille
  • Paris, France
    • Hôpital Necker - Enfants Malades
  • Strasbourg, France
    • Hopital de Hautepierre
• India
  • Dehli
    • New Delhi, Dehli, India, 110029
      • All India Institute of Medical Sciences
  • Karnataka
    • Bangalore, Karnataka, India, 560029
      • Indira Gandhi Institute of Child Health
  • Kerala
    • Kochi, Kerala, India, 682041
      • Amrita Advanced Centre for Epilepsy
  • Maharashtra
    • Pune, Maharashtra, India, 411043
      • Bharati Vidyapeeth Deemed University - Bharati Hospital
• Italy
  • Ancona, Italy
    • Azienda Ospedaliero Universitaria
  • Ancona, Italy
    • Pediatric Hospital G. Salesi
  • Firenze, Italy
    • AOU Anna Meyer - Clinica di Neurologia Pediatrica
  • Genova, Italy
    • Istituto Pediatrico Giannina Gaslini
  • Milano, Italy
    • Ospedale dei Bambini Vittore Buzzi
  • Neapel, Italy
    • Università Degli Studi Di Napoli Federico Ii
  • Roma, Italy
    • Ospedale Pediatrico Bambino Gesù
  • Roma, Italy
    • Policlinico Universitario A.Gemelli
  • Verona, Italy
    • Azienda Ospedaliera Universitaria integrata
• Mexico
  • Culiacán, Mexico
    • Neurociencias Estudios Clinicos S.C.
  • Mexico City, Mexico
    • HSRT
  • Nuevo León, Mexico, 66278
    • Tecnologico De Monterrey - Hospital Zambrano Hellion - Instituto de Neurologia y Neurocirugia
• Poland
  • Warsaw, Poland, 02-091
    • Medical University of Warsaw
  • Warsaw, Poland
    • Institute of Mother and Child
  • Gdansk
    • Gdańsk, Gdansk, Poland
      • The University Clinical Center
  • Krakow
    • Kraków, Krakow, Poland
      • Provincial Specialist Children's Hospital st. Ludwika
• Spain
  • Barcelona, Spain, 8041
    • Hospital de la Santa Creu i Sant Pau
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045-7106
      • The Childrens Hospital Colorado
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital for Children
    • Orlando, Florida, United States, 32803
      • Advent Health Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Childrens Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Hospital
  • Massachusetts
    • Lexington, Massachusetts, United States, 02420
      • Children's Brain Institute
  • Michigan
    • Detroit, Michigan, United States, 48201-2119
      • Children's Hospital of Michigan
  • New York
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital, North
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center - PPDS
  • Texas
    • Dallas, Texas, United States, 75207
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 2 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has been diagnosed with IS within 6 weeks prior to Screening. Diagnostic criteria include both clinical spasms and an EEG pattern consistent with hypsarrhythmia or significant abnormality compatible with IS
• Participant has normal renal function as defined by an estimated glomerular filtration rate (eGFR) greater than [>] 60 milliliter/minute (mL/min)/1.73 m^2, calculated as eGFR = 0.413 × (height [Centimeter (cm)]/serum creatinine [milligrams per deciliter {mg/dL}])
• Participant's legally authorized representative (that is [i.e.], parent or guardian) must provide written informed consent obtained per Institutional Review Board (IRB) policy and requirements, consistent with the International Council for Harmonisation (ICH)
• Participant's parent/guardian is able to understand and willing to comply with study procedures and restrictions

Exclusion Criteria:

• Participant has been diagnosed with tuberous sclerosis
• Participant has acute illness considered clinically significant by the Investigator within 30 days prior to Screening
• Participant 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
• Participant has a preplanned surgery or procedure(s) that would interfere with the conduct of the study
• Participant has received any prior treatment for IS
• Participant has been previously treated with adrenocorticotropic hormone (ACTH), corticosteroids, or Vigabatrin for seizures;
• Participant has been previously treated with a course of corticosteroids for an indication other than seizures within 30 days prior to Screening
• Participant has a known or suspected allergy to ACTH or Vigabatrin or any component of AMZ002 or Vigabatrin
• Participant 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)
• Participant' s parent/guardian is unable to provide written informed consent and/or to complete the daily diary
• Participant has any other disease, condition, or therapy that, in the opinion of the Investigator, might compromise safety or compliance, preclude the participant from successfully completing the study, or interfere with the interpretation of the results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vigabatrin	Drug: Vigabatrin, oral; Oral administration
Experimental: AMZ002	Drug: AMZ002 injectable solution, 0.5mg/mL; Injectable solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants with Absence of Clinical Spasms as Assessed by Video Electroencephalogram (EEG) at Day 14	At Day 14
Proportion of Participants with Resolution of Hypsarrhythmia or Significant Abnormality Compatible with Infantile Spasms (IS) as Assessed by Video EEG at Day 14	At Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Time from Treatment Initiation to Absence of Clinical Spasms as Assessed by Parent/Guardian Diary	Baseline up to Day 58
Proportion of Participants with Absence of Clinical Spasms as Assessed by Parent/Guardian Diary at Day 14	At Day 14
Proportion of Participants with Recurrence of Clinical Spasms After Initial Response as Assessed by Video EEG/ by Parent/Guardian Diary	From Day 14 up to Day 58
Time from Initial Response to Recurrence of Clinical Spasms	From Day 14 up to Day 58

Collaborators and Investigators

• Sponsor: Amzell

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 9, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: April 18, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Central Nervous System Diseases; Seizures; Infantile spasms; Vigabatrin; West syndrome; AMZ002; Electroencephalograms; Epileptic Syndrome
• 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; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; GABA Agents; Anticonvulsants; Vigabatrin
• Other Study ID Numbers: AMZ002-002; 2021-003015-26 (EudraCT Number)

Drug and device information, study documents

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