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)
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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT07082725
Intervention or treatment
DRUG: Nizubaglustat
DRUG: Placebo
Conditions
- Niemann-Pick Type C Disease
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Research sites nearby
Closest Location:
Women's and Children's Hospital
Select from list below to view details:
Women's and Children's Hospital
North Adelaide, South Australia, Australia
Royal Children's Hospital Melbourne - PIN
Parkville, Victoria, Australia
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Who is running the clinical trial?
Azafaros A.G.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Nizubaglustat
| Drug: Nizubaglustat |
PLACEBO_COMPARATOR: Placebo
| Drug: Placebo |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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 | Baseline to month 18 |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in SARA score for gait/posture | Assessed on a 9-point scale with higher scores indicating inability to complete the task | 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 | 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 | 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 | 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 | Baseline to months 6, 12, and 18 |
| Change from baseline in 9-Hole Peg Test (9-HPT-D) | Assessed by the number of pegs per second placed in a 50-second, 9-HPT using the dominant hand | Baseline to months 6, 12, and 18 |
| Change from baseline in NPC-Clinical Severity Scale (NPC-CSS) | Scores can range from 0 to 61, with a higher score indicating more severe clinical impairment | Baseline to months 6, 12, and 18 |
| Change from baseline in Goal Attainment scale (GAS) | Assesses individual goals achieved during the study | Baseline to months 6, 12, and 18 |
| Change from baseline in Clinician Global Impression of Change (CGI-C) | Assessed on a 7-point scale with higher scores indicating lower improvement | Baseline to months 6, 12, and 18 |
| Change from baseline in Participant/Caregiver Global Impression of Change (PGI-C) | Assessed on a 7-point scale with higher scores indicating lower improvement | Baseline to months 6, 12, and 18 |
| Change from baseline in Seizure frequency and duration, as per the seizure diary | Not Specified | 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 | Not Specified | Baseline to month 18 |
| Time-to-event comparison between nizubaglustat and placebo over the study duration for pre-defined detrimental events of an increase in functional SARA of ≥1.5 points | Not Specified | Baseline to month 18 |
| Time-to-event comparison between nizubaglustat and placebo over the study duration for pre-defined detrimental events of a decrease in PAS of ≥1 point | Not Specified | Baseline to month 18 |
| Time-to-event comparison between nizubaglustat and placebo over the study duration for pre-defined detrimental events of participants leaving the study due to participant/caregiver perception of disease progression/lack of efficacy | Not Specified | Baseline to month 18 |
| Maximum observed plasma concentration (Cmax) | Not Specified | Baseline and months 1,18, and 21 |
| Time to Cmax (Tmax) | Not Specified | Baseline and months 1,18, and 21 |
| Plasma trough concentration (Ctrough) | Not Specified | Baseline and month 1 |
| Area under the plasma concentration-time curve from time of dosing (zero) to 24 hours post-dose (AUC0-24) at baseline | Not Specified | Baseline (Day 1) |
| Accumulation ratio for Cmax | Not Specified | Baseline and months 1,18, and 21 |
| Change from baseline in plasma concentration of glucosylceramide (GlcCer) C16:0; C18:0 | Not Specified | Baseline and months 1, 6, 12, and 18 |
References
Clinical Trials Gov: 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)Other trials to consider
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