A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease (NPC)

Official title

18-month Double-blind, Randomized, Placebo-controlled, Multicenter, Phase 3 Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease and in Late-infantile and Juvenile-onset Forms of GM1 Gangliosidosis or GM2 Gangliosidosis

Overview

An 18-month double-blind, randomized, placebo-controlled, multicenter, Phase 3 study to evaluate the safety and efficacy of oral nizubaglustat (AZ-3102) in late-infantile and juvenile forms of Niemann-Pick type C disease

Detailed description

Please see NCT #07054515 for information on the AZA-001-301 Master Protocol

PRIMARY OBJECTIVE

The primary objective of this study is to demonstrate superior efficacy on ataxic manifestations with oral nizubaglustat dosing compared with placebo when administered over 18 months in participants with late-infantile and juvenile forms of NPC disease

SECONDARY OBJECTIVES

I. To assess additional efficacy in ataxic and non-ataxic manifestations comparing nizubaglustat dosing with placebo when administered over 18 months in participants with late-infantile and juvenile forms of NPC disease

II. To assess the pharmacokinetic (PK) properties of nizubaglustat after administration of the first dose (Visit 1) and at steady state after multiple once daily doses

III. To assess the pharmacodynamic (PD) effects of nizubaglustat

IV. To assess the safety and tolerability of daily oral nizubaglustat dosing compared with placebo, when administered over 18 months in participants with late-infantile and juvenile forms of NPC disease

Interventions

• Drug Nizubaglustat
  AZ-3102
• Drug Placebo
  Matching placebo

Primary outcome measures

• Change from baseline in total Scale for the Assessment and Rating of Ataxia (SARA) score [Time frame: Baseline to month 18]
• Change from baseline in functional SARA score [Time frame: Baseline to month 18]

Secondary outcome measures (12)

• Change from baseline in SARA score for gait/posture [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in SARA score for speech [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in SARA score for kinetics [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in Vineland Adaptive Behavior Scale (VABS) [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in Penetration-Aspiration Scale (PAS) [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in 9-Hole Peg Test (9-HPT-D) [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in NPC-Clinical Severity Scale (NPC-CSS) [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in Goal Attainment scale (GAS) [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in Clinician Global Impression of Change (CGI-C) [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in Participant/Caregiver Global Impression of Change (PGI-C) [Time frame: Baseline to months 6, 12, and 18]
• Change from baseline in Seizure frequency and duration, as per the seizure diary [Time frame: Baseline to months 6, 12, and 18]
• Time-to-event comparison between nizubaglustat and placebo over the study duration for pre-defined detrimental events of an increase in total SARA score of ≥2 points [Time frame: Baseline to month 18]

Eligibility criteria

Inclusion criteria

• Signed informed consent
• Confirmed diagnosis of NPC disease
• Patient is unable or unwilling to take miglustat, or is, in the opinion of the investigator, unsatisfactorily treated with miglustat
• Male and female participants aged 4 years and older at the time of informed consent
• Onset of neurological symptoms from 2 to 15 years
• Disability level at Baseline: Ataxic disturbances with a total SARA score of ≥3 and ≤30 at Baseline
• Female of childbearing potential who are sexually active willing to follow the contraceptive guidance
• Male participants with a female partner of childbearing potential willing to follow the contraceptive guidance

Exclusion criteria

• A history of medical conditions other than NPC disease that, in the opinion of the Principal Investigator, would confound scientific rigor or the interpretation of results
• Body weight of <10 kg
• The presence of another neurologic disease
• The presence of moderate or severe hepatic impairment
• The presence of moderate or severe renal impairment
• Platelet count of <100x10\^9/L
• The dose of any anti-epileptic treatment(s) was not stable (required a change in dose within the previous 3 months) and/or a new anti-epileptic treatment (drug or procedure) was prescribed in the month before Baseline
• Prior use of an investigational drug within the 3 months before Screening; or prior participation in a clinical study involving gene therapy or stem cell transplantation within 2 years prior to Screening
• A positive serum pregnancy test (for women of childbearing potential)
• Current treatment with miglustat, provided the patient has been using the recommended dose for most of the past 12 months AND is, in the opinion of the investigator, satisfactorily treated with miglustat. Any participants receiving miglustat are required to undergo a 1-month washout period before starting study medication

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 5 centers

• UCSF Children's Hospital and Research Center at Oakland — Oakland
• University of Minnesota Medical School — Minneapolis
• Mayo Clinic Children's Center - PIN — Rochester
• Children's Medical Center Dallas — Dallas
• Lysosomal Rare Disorders Research and Treatment Center — Fairfax

India · 4 centers

• Amrita Institute of Medical Sciences and Research Centre — Ernākulam
• All India Institute of Medical Sciences (AIIMS) - New Delhi — New Delhi
• JK Lone Hospital — Jaipur
• Christian Medical College and Hospital — Vellore

Australia · 3 centers

• Women's and Children's Hospital — North Adelaide
• Royal Melbourne Hospital — Parkville
• Royal Children's Hospital Melbourne - PIN — Parkville

Brazil · 3 centers

• Instituto Fernandes Figueira — Rio de Janeiro
• Hospital de Clinicas de Porto Alegre (HCPA) - PPDS — Porto Alegre
• Hospital Pequeno Principe — Curitiba

Canada · 3 centers

• M.A.G.I.C. Clinic Ltd. Metabolics and Genetics in Calgary — Calgary
• University of Alberta Medical Genetics Clinic — Edmonton
• Centre Hospitalier de l'Universite de Montreal-1000 rue Saint-Denis — Montreal

Turkey (Türkiye) · 3 centers

• Balcali Hastanesi Saglik Uygulama ve Arastirma Merkezi — Adana
• Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi — Çankaya
• Ege Universitesi Tip Fakultesi — Bornova

United Kingdom · 3 centers

• Great Ormond Street Hospital — London
• University College London Hospitals (UCLH) — London
• Royal Manchester Children's Hospital — Manchester

Mexico · 2 centers

• Hospital Universitario Dr. Jose Eleuterio González — Monterrey
• Centenario Hospital Miguel Hidalgo — Aguascalientes

Spain · 2 centers

• Hospital Universitario Vall d'Hebron - PPDS — Barcelona
• Hospital Infantil Universitario Niño Jesus - PIN — Madrid

Argentina · 1 center

• Hospital de Niños de La Santisima Trinidad — Córdoba

Germany · 1 center

• SphinCS GmbH — Höchheim

Italy · 1 center

• Fondazione IRCCS Istituto Neurologico Carlo Besta — Milan

Pakistan · 1 center

• The Children's Hospital & the University of Child Health Lahore — Lahore

Portugal · 1 center

• ULS de Santo António, EPE - Centro Materno Infantil Norte — Porto

Switzerland · 1 center

• Inselspital - Universitätsspital Bern — Bern

Identifiers

NCT: NCT07082725 · AZA-001-301-NPC · 2024-515778-28-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗