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

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

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