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NIZUBAGLUSTAT

Nizubaglustat (also known as AZ-3102) is currently being studied as a potential treatment for Niemann-Pick Type C disease (NPC), a rare genetic disorder that affects the body’s ability to transport cholesterol and other fatty substances. A phase 3 clinical trial is underway to evaluate this oral medication’s safety and effectiveness in patients with late-infantile and juvenile forms of NPC. The 18-month study is designed as a double-blind, randomized, placebo-controlled trial across multiple centers, focusing particularly on how the drug may improve ataxic symptoms (problems with movement coordination) that significantly impact patients’ quality of life. This research represents an important step in developing treatments for this challenging neurodegenerative condition.

Table of Contents

What is Nizubaglustat?

Nizubaglustat, also known as AZ-3102, is an investigational oral medication being studied for the treatment of Niemann-Pick Type C disease (NPC), specifically in late-infantile and juvenile forms of the condition[1]. The drug is currently in Phase 3 clinical trials, which is an advanced stage of testing that occurs before a medication can be approved for widespread use.

Based on the available clinical trial information, Nizubaglustat appears to work by affecting certain biological processes related to the disease. While the exact mechanism isn’t explicitly stated in the trial description, the study is measuring changes in glucosylceramide (GlcCer) levels, which suggests the drug may work by modifying lipid metabolism in the body[1].

What is Niemann-Pick Type C Disease?

Niemann-Pick Type C disease is a rare genetic disorder that affects how the body processes fats (lipids). In this condition, harmful amounts of lipids accumulate in the spleen, liver, lungs, brain, and other organs. This accumulation leads to progressive deterioration of the nervous system and various other symptoms[1].

The clinical trial specifically focuses on patients with late-infantile and juvenile forms of NPC. These terms refer to when symptoms typically begin to appear:

  • Late-infantile form: Symptoms usually begin to show between 2 and 6 years of age
  • Juvenile form: Symptoms typically appear between 6 and 15 years of age

NPC often presents with movement problems, particularly ataxia (lack of muscle coordination), which is a major focus of the Nizubaglustat clinical trial[1].

Current Clinical Trial Information

The main clinical trial for Nizubaglustat is an 18-month study described as “double-blind, randomized, placebo-controlled, multicenter, Phase 3”[1]. Let’s break down what this means:

  • Double-blind: Neither the participants nor the doctors know who is receiving the actual drug or the placebo during the study
  • Randomized: Participants are randomly assigned to either receive Nizubaglustat or a placebo
  • Placebo-controlled: Some participants receive an inactive substance (placebo) instead of the medication, which helps determine if the drug is truly effective
  • Multicenter: The study is being conducted at multiple medical facilities
  • Phase 3: This is an advanced stage of clinical testing that focuses on confirming effectiveness, monitoring side effects, and comparing to commonly used treatments

The primary objective of this study is to demonstrate if Nizubaglustat is more effective than placebo in treating ataxic manifestations (movement coordination problems) in people with late-infantile and juvenile forms of NPC disease over an 18-month period[1].

How Nizubaglustat is Administered

According to the clinical trial information, Nizubaglustat is given as once daily oral dispersible tablets[1]. “Dispersible” means the tablets can dissolve in liquid, which may make them easier to take, particularly for younger patients or those who have difficulty swallowing pills.

The trial is comparing this medication against a matching placebo, which looks the same but contains no active medication. This helps researchers determine if any improvements seen are truly due to the drug and not just the expectation of improvement (known as the placebo effect)[1].

How the Treatment’s Effectiveness is Measured

The clinical trial uses several measurements to evaluate how well Nizubaglustat works. The primary measurements focus on ataxia (coordination problems), which is a major symptom of NPC disease[1].

Primary Outcome Measures:

  • Total Scale for the Assessment and Rating of Ataxia (SARA) score: This measures eight categories of ataxia symptoms, with scores ranging from 0 (no ataxia) to 40 (most severe ataxia)[1]
  • Functional SARA score: An abbreviated scale scoring from 0 to 16, with higher scores indicating more severe impairment[1]

Secondary Outcome Measures:

The trial also looks at many other aspects of how the medication might help, including[1]:

  • Specific SARA components: Changes in gait/posture, speech, and movement (kinetics)
  • Adaptive behavior: Using the Vineland Adaptive Behavior Scale (VABS) to assess communication, daily living skills, socialization, and motor skills
  • Swallowing function: Using the Penetration-Aspiration Scale (PAS) to evaluate swallowing safety
  • Fine motor skills: Using the 9-Hole Peg Test to measure hand dexterity
  • Overall disease severity: Using the NPC-Clinical Severity Scale (NPC-CSS)
  • Individual goal achievement: Using the Goal Attainment Scale (GAS)
  • Global impressions of change: Both from clinicians (CGI-C) and participants/caregivers (PGI-C)
  • Seizure frequency and duration: As recorded in seizure diaries

The study also tracks how long it takes for certain negative events to occur, such as worsening scores on the various tests. This helps determine if the medication can delay disease progression[1].

Safety and Monitoring

The clinical trial includes several measures to monitor the safety and how the body processes Nizubaglustat[1]:

Pharmacokinetic (PK) Properties:

These measurements show how the drug moves through the body[1]:

  • Maximum observed plasma concentration (Cmax): The highest level of the drug in the bloodstream
  • Time to Cmax (Tmax): How long it takes to reach the maximum concentration
  • Plasma trough concentration (Ctrough): The lowest level between doses
  • Area under the plasma concentration-time curve (AUC0-24): A measure of total drug exposure over 24 hours
  • Accumulation ratio: How much the drug builds up in the system over time

Pharmacodynamic (PD) Effects:

The trial measures changes in glucosylceramide (GlcCer) levels in the blood. GlcCer is a type of lipid (fat) that may be involved in the disease process of NPC. By measuring changes in these levels, researchers can see how the drug affects the underlying biology of the disease[1].

While the clinical trial information doesn’t detail specific side effects, safety and tolerability are listed as important aspects being evaluated throughout the 18-month study period[1].

Study Aspect Details
Drug Name Nizubaglustat (AZ-3102)
Condition Being Treated Niemann-Pick Type C Disease (late-infantile and juvenile forms)
Study Design 18-month double-blind, randomized, placebo-controlled, multicenter, Phase 3 study
Administration Once daily oral dispersible tablets
Primary Objectives To demonstrate superior efficacy on ataxic manifestations compared to placebo
Primary Outcome Measures Change from baseline in total SARA score (0-40 scale)
Change from baseline in functional SARA score (0-16 scale)
Key Secondary Outcomes Changes in gait/posture, speech, and fine motor skills
Adaptive behavior and swallowing function
Overall disease severity and goal achievement
Time to symptom worsening
Drug concentration and effects in the body
Assessment Timepoints Baseline and months 6, 12, and 18

FAQ

  • What is Nizubaglustat and how is it being tested? Nizubaglustat (AZ-3102) is an investigational oral medication being studied as a potential treatment for Niemann-Pick Type C disease. It's being tested in a Phase 3 clinical trial that lasts 18 months. The study is 'double-blind' (neither patients nor researchers know who receives the actual drug), 'randomized' (participants are randomly assigned to either the drug or placebo group), and 'placebo-controlled' (results are compared against an inactive substance). Patients take the medication as once-daily oral dispersible tablets.
  • What is Niemann-Pick Type C disease? Niemann-Pick Type C disease (NPC) is a rare genetic disorder where the body cannot properly transport cholesterol and other fatty substances (lipids) inside cells. This leads to an abnormal accumulation of these substances in various tissues, including the brain. The trial specifically focuses on late-infantile and juvenile forms of NPC, which typically appear in childhood. NPC is progressive and affects movement coordination (causing ataxia), speech, swallowing, and other neurological functions.
  • What are the main goals of this clinical trial? The primary goal of the trial is to determine if Nizubaglustat is better than placebo at improving ataxic manifestations (movement coordination problems) in patients with late-infantile and juvenile forms of NPC disease over 18 months. Secondary goals include assessing additional benefits for both ataxic and non-ataxic symptoms, understanding how the drug moves through the body (pharmacokinetics), measuring its biological effects (pharmacodynamics), and confirming its safety and tolerability when taken daily for 18 months.
  • How are they measuring if the drug works? The main measurements focus on changes in the Scale for the Assessment and Rating of Ataxia (SARA). This includes both the total SARA score (ranging from 0-40, with higher scores indicating worse ataxia) and a functional SARA score (ranging from 0-16). Additional measurements include specific aspects of SARA (gait/posture, speech, and kinetics), adaptive behavior (VABS), swallowing function (PAS), fine motor skills (9-Hole Peg Test), overall disease severity (NPC-CSS), goal achievement, and impressions of change from both clinicians and patients/caregivers. They're also tracking seizure frequency and how long it takes for symptoms to worsen.
  • What happens to participants during the trial? Participants are randomly assigned to receive either Nizubaglustat or a matching placebo as daily oral dispersible tablets for 18 months. Throughout the study, they undergo regular assessments to measure changes in their symptoms, particularly focusing on movement coordination (ataxia). Researchers collect blood samples to understand how the drug moves through the body and its effects. They also monitor for any side effects or safety concerns. Various tests measure changes in movement, speech, swallowing, adaptive behavior, and overall disease progression. The study includes assessments at baseline and at months 6, 12, and 18 to track changes over time.

Ongoing Clinical Trials on NIZUBAGLUSTAT

  • Study on the Effectiveness and Safety of Nizubaglustat in Patients with Niemann-Pick Type C, GM1, or GM2 Gangliosidosis

    Recruiting

    1 1
    Investigated drugs:
    France Germany Italy Portugal Spain Sweden

Glossary

  • Niemann-Pick Type C Disease (NPC): A rare, inherited genetic disorder where the body cannot properly transport cholesterol and other fatty substances within cells, leading to their abnormal accumulation in various tissues, particularly the brain. This causes progressive neurological decline.
  • Nizubaglustat (AZ-3102): The investigational drug being studied in this clinical trial as a potential treatment for Niemann-Pick Type C disease.
  • Ataxia: A neurological symptom that involves problems with movement coordination, balance, and precision. It's a major symptom of NPC disease being targeted by this treatment.
  • Double-blind: A study design where neither the participants nor the researchers know who is receiving the actual drug versus placebo, helping to prevent bias in evaluating results.
  • Randomized: The process of randomly assigning participants to either the treatment group (receiving the drug) or control group (receiving placebo), which helps ensure the groups are comparable.
  • Placebo-controlled: A study design that compares the effects of the investigational drug against an inactive substance (placebo) that looks identical, allowing researchers to determine if the drug's effects are real.
  • Phase 3 trial: A large-scale clinical study conducted to confirm effectiveness, monitor side effects, and compare to commonly used treatments. It's typically one of the final stages before seeking drug approval.
  • Scale for the Assessment and Rating of Ataxia (SARA): A clinical measurement tool used to evaluate the severity of ataxia (coordination problems). The total SARA score ranges from 0 (no ataxia) to 40 (most severe ataxia).
  • Functional SARA: An abbreviated version of the SARA scale that scores from 0 to 16, focusing on the most functionally relevant aspects of ataxia, with higher scores indicating more severe impairment.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including how it's absorbed, distributed, metabolized, and eliminated.
  • Pharmacodynamics (PD): The study of a drug's effects on the body, including its biochemical and physiological effects and mechanisms of action.
  • Oral dispersible tablets: A form of medication that dissolves quickly in the mouth, making it easier to take, particularly for patients who may have difficulty swallowing.
  • Vineland Adaptive Behavior Scale (VABS): An assessment tool that measures adaptive functioning in four domains: communication, daily living skills, socialization, and motor skills.
  • Penetration-Aspiration Scale (PAS): An 8-point scale that assesses swallowing function and the risk of food or liquid entering the airway, with higher scores indicating more severe problems.
  • 9-Hole Peg Test (9-HPT-D): A test that measures fine motor coordination by timing how quickly a person can place and remove pegs in a board, providing information about dexterity.
  • NPC-Clinical Severity Scale (NPC-CSS): A disease-specific scale that measures the overall severity of Niemann-Pick Type C disease across multiple domains, with scores ranging from 0 to 61 (higher scores indicate more severe impairment).
  • Goal Attainment Scale (GAS): A method to evaluate progress toward individualized goals set for each participant at the beginning of the study.
  • Clinician Global Impression of Change (CGI-C): A 7-point scale where healthcare providers rate their perception of how much a patient's condition has changed during treatment.
  • Participant/Caregiver Global Impression of Change (PGI-C): Similar to the CGI-C, but rated by patients or their caregivers, providing their perspective on changes in the condition.
  • Late-infantile and juvenile forms: Classifications of NPC disease based on when symptoms first appear. Late-infantile typically refers to onset between 2-6 years of age, while juvenile refers to onset between 6-15 years.
  • Glucosylceramide (GlcCer): A type of glycosphingolipid (fat molecule) that can accumulate in NPC disease. Changes in its levels are being measured as a pharmacodynamic marker in this study.

References

  1. https://clinicaltrials.gov/study/NCT07082725