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Active, not recruitingNCT07082543Updated Sep 22, 2026

A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of GM1 Gangliosidosis or GM2 Gangliosidosis

A Phase 3 interventional study of AZ-3102 and Placebo in Gangliosidoses, GM2 and Gangliosidosis, GM1, sponsored by Azafaros B.V.. Active, not recruiting at 27 sites in 14 countries. Open to participants aged 4 Years and older. Per ClinicalTrials.gov, last updated 2026-09-22.

Sponsored by Azafaros B.V. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
75
Allocation
Randomized
Ages
4 Years and older
Sex
All
01

Study summary

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 GM1 gangliosidosis or GM2 gangliosidosis

Read the 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 GM1/GM2 gangliosidosis

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 GM1/GM2 gangliosidosis

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 GM1/GM2 gangliosidosis

02

Conditions studied

  • Gangliosidoses, GM2
  • Gangliosidosis, GM1

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Keywords

  • Nizubaglustat
03

Who can participate

Ages eligible
4 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Confirmed GM1 gangliosidosis or Tay-Sachs, Sandhoff, or GM2AB variant
  • Male and female participants aged 4 years and older at the time of informed consent
  • Onset of neurological symptoms from 1 to 10 years
  • Disability level at Baseline: Ataxic disturbances with a total SARA score of ≥3 and ≤30 at Baseline
  • Females 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

Exclusion Criteria:

  • A history of medical conditions other than GM1 or GM2 gangliosidosis 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)
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
75 participants (estimated)

Study arms

  • Experimental
    Nizubaglustat

    Once daily oral dispersible tablets

    Drug: AZ-3102

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

  • DrugAZ-3102

    Nizubaglustat

  • DrugPlacebo

    Placebo

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

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

  6. 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

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

  7. Change from baseline in Goal Attainment Scale (GAS)

    Assesses individual goals achieved during the study

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

  8. Change from baseline in Clinician Global Impression of Change (CGI-C)

    Assessed on a 7-point scale with higher scores indicating lower improvement

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

  9. Change from baseline in Participant/Caregiver Global Impression of Change (PGI-C)

    Assessed on a 7-point scale with higher scores indicating lower improvement

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

  10. Change from baseline in Seizure frequency and duration, as per the seizure diary

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

  11. 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

  12. Time-to-event comparison between nizubaglustat and placebo over the course of the study for pre-defined detrimental events of an increase in functional SARA of ≥1.5 points

    Time frame: Baseline to month 18

  13. 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

    Time frame: Baseline to month 18

  14. 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

    Time frame: Baseline to month 18

  15. Maximum observed plasma concentration (Cmax)

    Time frame: Baseline and months 1,18, and 21

  16. Time to Cmax (Tmax)

    Time frame: Baseline and months 1,18, and 21

  17. Plasma trough concentration (Ctrough)

    Time frame: Baseline and month 1

  18. Area under the plasma concentration-time curve from time of dosing (zero) to 24 hours post-dose (AUC0-24) at baseline

    Time frame: Baseline (Day 1)

  19. Accumulation ratio for Cmax

    Time frame: Baseline and months 1,18, and 21

  20. Change from baseline in plasma concentration of glucosylceramide (GlcCer) C16:0; C18:0

    Time frame: Baseline to months 1, 6, 12, and 18

06

Study locations

27 sites
  • UCSF Children's Hospital and Research Center at Oakland
    Oakland, California 94609, United States
  • University of Minnesota Medical School
    Minneapolis, Minnesota 55455, United States
  • Mayo Clinic Children's Center - PIN
    Rochester, Minnesota 55905, United States
  • Children's Medical Center Dallas
    Dallas, Texas 75235, United States
  • Lysosomal Rare Disorders Research and Treatment Center
    Fairfax, Virginia 22030-7404, United States
  • Hospital Universitario Austral
    Ciudad Autónoma Buenos Aires, Buenos Aires B1629AHJ, Argentina
  • Hospital de Niños de La Santisima Trinidad
    Córdoba, Córdoba Province X5004 ASL, Argentina
  • Women's and Children's Hospital
    North Adelaide, South Australia 5006, Australia
  • Instituto Fernandes Figueira
    Rio de Janeiro, Rio de Janeiro 22250-020, Brazil
  • Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
    Porto Alegre, Rio Grande do Sul 90560-030, Brazil
  • M.A.G.I.C. Clinic Ltd. Metabolics and Genetics in Calgary
    Calgary, Alberta T3B 6A8, Canada
  • AP-HP - Hôpital Armand Trousseau
    Paris, 75012, France
  • AP-HP - Hôpital de la Pitié Salpétrière
    Paris, France
  • SphinCS GmbH
    Höchheim, 65239, Germany
  • Amrita Institute of Medical Sciences and Research Centre
    Ernākulam, Kerala 682041, India
  • All India Institute of Medical Sciences (AIIMS) - New Delhi
    New Delhi, National Capital Territory of Delhi 110029, India
  • JK Lone Hospital
    Jaipur, Rajasthan 302004, India
  • Fondazione IRCCS Istituto Neurologico Carlo Besta
    Milan, 20133, Italy
  • ULS de Santo António, EPE - Centro Materno Infantil Norte
    Porto, Porto District 4050-651, Portugal
  • ULS de Santa Maria,EPE - Hospital de Santa Maria - PPDS
    Lisbon, 1649-035, Portugal
  • Hospital Universitario Vall d'Hebron - PPDS
    Barcelona, Barcelona 8035, Spain
  • Hospital Infantil Universitario Niño Jesus - PIN
    Madrid, Madrid 28009, Spain
  • Sahlgrenska universitetssjukhuset Östra
    Gothenburg, Västra Götaland County 416 50, Sweden
  • Inselspital - Universitätsspital Bern
    Bern, Canton of Bern 3010, Switzerland
  • Balcali Hastanesi Saglik Uygulama ve Arastirma Merkezi
    Adana, Adana 1250, Turkey (Türkiye)
  • Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi
    Çankaya, Ankara 6500, Turkey (Türkiye)
  • Ege Universitesi Tip Fakultesi
    Bornova, İzmir 35100, Turkey (Türkiye)
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07082543
Lead sponsor
Azafaros B.V.
Responsible party
Sponsor
First posted
Jul 24, 2025
Start date
Jun 30, 2025
Primary completion
Feb 6, 2028 (estimated)
Completion
Mar 6, 2028 (estimated)
Last update
Sep 22, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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