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)

Phase 3RecruitingNCT07082725

Azafaros A.G.72 enrolled

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

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Niemann-Pick Type C Disease

Interventions

NizubaglustatDRUG

AZ-3102

PlaceboDRUG

Matching placebo

Eligibility

Sex: ALLMin age: 4 Years

Medical Language ↔ Plain English

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

Locations (30)

Outcomes

Primary Outcomes

Change from baseline in total Scale for the Assessment and Rating of Ataxia (SARA) score

Total SARA comprises eight categories with a cumulative score ranging from 0 (no ataxia) to 40 (most severe ataxia)

Time frame: Baseline to month 18

Change from baseline in functional SARA score

Functional SARA uses an abbreviated scale that scores 0 to 16, with higher scores indicating more severe impairment

Time frame: Baseline to month 18

Secondary Outcomes

Change from baseline in SARA score for gait/posture

Assessed on a 9-point scale with higher scores indicating inability to complete the task

Time frame: Baseline to months 6, 12, and 18

Change from baseline in SARA score for speech

Assessed on a 7-point scale with higher scores indicating unintelligible speech/anarthria

Time frame: Baseline to months 6, 12, and 18

Change from baseline in SARA score for kinetics

Assessed on a 5-point scale with higher scores indicating more severe impairment

Time frame: Baseline to months 6, 12, and 18

Change from baseline in Vineland Adaptive Behavior Scale (VABS)

Assesses four domains of function: communication, daily living skills, socialization, and motor skills

Time frame: Baseline to months 6, 12, and 18

Change from baseline in Penetration-Aspiration Scale (PAS)

Assessed on an 8-point ordinal scale, with 1 representing the lowest and 8 the highest/most severe score

Central Contacts

Patient Advocacy Representative

CONTACT

Please reach out by email info@azafaros.com

Contact for Healthcare Professionals

CONTACT

Please reach out by email medinfo@azafaros.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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Royal Children's Hospital Melbourne - PIN

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...and 20 more locations