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1. A study to see how well nizubaglustat (AZ-3102) works in participants with GM1 gangliosidosis or GM2 gangliosidosis and how safe it is 2. A study to see how well nizubaglustat (AZ-3102) works in participants with Niemann-Pick type C disease and how safe it is
EU CTIS ID: 2024-515778-28-00
What this study is testing
To demonstrate superior efficacy on ataxic manifestations with oral nizubaglustat dosing compared with placebo when administered over 72 weeks in participants with late-infantile and juvenile forms of NPC disease or late-infantile/juvenile-onset forms of GM1 or GM2 gangliosidosis.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. Provide written informed consent signed by the participant or their legal guardian, or parent. The parent and/or legal guardian can read, understand, and sign informed consent. Where appropriate, assent will also be sought for participants aged <18 years. If a participant reaches the age of legal consent during the study, they will be re-consented at the next scheduled visit upon attaining that age.
- 6. Willing and able to complete assessments.
- 7. Able to take study medication.
- 8. Females of childbearing potential (defined as a premenopausal female capable of becoming pregnant) are eligible if: • sexually inactive and willing to stay inactive during the study (sexual abstinence for the 14 days prior to the first study drug dose and confirmation of continued abstinence until 28 days after the last dose) • using one of the following highly-effective contraceptives (i.e. <1% failure rate when used consistently and correctly) for 14 days prior to the first study drug dose and continuing until 28 days after the last dose: intrauterine device; surgical sterilization of the partner (vasectomy for a minimum of 6 months); combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable or intrauterine hormone releasing system).
- 9. Females of non-childbearing potential • who have undergone one of the following sterilization operations at least 6 months prior to receiving the first dose of study drug: hysteroscopic sterilization, bilateral salpingectomy, hysterectomy, bilateral oophorectomy OR • who are postmenopausal with at least 1 year of amenorrhea and follicle stimulating hormone (FSH) serum values consistent with postmenopausal status. At Screening postmenopausal women will have their FSH levels analyzed and central laboratory FSH levels should fall within the postmenopausal range. "• are pre-menarchal at Screening and agree to stay sexually inactive during the study and until 28 days after the last dose or are using one of the contraceptive methods listed in inclusion criterion 8.
- 14. For subprotocol AZA-001-301-NPC only: Patient is unable or willing to take miglustat, or is, in the opinion of the investigator, unsatisfactorily treated with miglustat.
You likely can't join if
- 1. Any condition at Baseline that, in the opinion of the Principal Investigator, could interfere with study assessments (e.g., severe infection, severe cognitive impairment).
- 13. ECG with an average QTcF (corrected QT interval using Fridericia’s formula) interval of >450 msec for males and of >470 msec for females.
- For subprotocol AZA-001-301-GMx only: 14. Received migulstat in the 12 months prior to Baseline, unless •the dose was lower than the maximum dose specified in the miglustat Summary of Product Characteristics for patients with NPC disease, OR •the total duration of miglustat dosing was less than 12 months. Any participants receiving miglustat are required to undergo a 1-month washout period before starting study medication."
- 15. Known allergy to azasugars or any study drug excipient.
- 16. Evidence of suicidal ideation with intent (Type 4 to 5) on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening; this requirement is only applicable to participants judged by the Principal Investigator to be cognitively capable of understanding the concept of suicide.
- 2. A history of medical conditions other than NPC or GM1 or GM2 gangliosidosis that, in the opinion of the Principal Investigator, would confound scientific rigor or the interpretation of results.
See the full eligibility criteria
Who can join
- 1. Provide written informed consent signed by the participant or their legal guardian, or parent. The parent and/or legal guardian can read, understand, and sign informed consent. Where appropriate, assent will also be sought for participants aged <18 years. If a participant reaches the age of legal consent during the study, they will be re-consented at the next scheduled visit upon attaining that age.
- 6. Willing and able to complete assessments.
- 7. Able to take study medication.
- 8. Females of childbearing potential (defined as a premenopausal female capable of becoming pregnant) are eligible if: • sexually inactive and willing to stay inactive during the study (sexual abstinence for the 14 days prior to the first study drug dose and confirmation of continued abstinence until 28 days after the last dose) • using one of the following highly-effective contraceptives (i.e. <1% failure rate when used consistently and correctly) for 14 days prior to the first study drug dose and continuing until 28 days after the last dose: intrauterine device; surgical sterilization of the partner (vasectomy for a minimum of 6 months); combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable or intrauterine hormone releasing system).
- 9. Females of non-childbearing potential • who have undergone one of the following sterilization operations at least 6 months prior to receiving the first dose of study drug: hysteroscopic sterilization, bilateral salpingectomy, hysterectomy, bilateral oophorectomy OR • who are postmenopausal with at least 1 year of amenorrhea and follicle stimulating hormone (FSH) serum values consistent with postmenopausal status. At Screening postmenopausal women will have their FSH levels analyzed and central laboratory FSH levels should fall within the postmenopausal range. "• are pre-menarchal at Screening and agree to stay sexually inactive during the study and until 28 days after the last dose or are using one of the contraceptive methods listed in inclusion criterion 8.
- 14. For subprotocol AZA-001-301-NPC only: Patient is unable or willing to take miglustat, or is, in the opinion of the investigator, unsatisfactorily treated with miglustat.
- 10. Non-vasectomized male participants are eligible if they consent to use a spermicide-impregnated condom or abstain from sexual activity until 90 days after the last dose of study medication; their female partner is required to consent to comply with this inclusion criterion.
- 11. A vasectomized male who had the procedure at least 6 months before starting the study is eligible if they consent to use a condom during sexual activity. A man vasectomized less than 6 months before commencement of the study must adhere to the same restrictions as a non-vasectomized male.
- 12. Male participants agree not to donate sperm from the start of study treatment until 90 days after the final dose. Female participants agree not to donate eggs from the start of treatment of treatment until 90 days after the final dose (though this would not be permitted because of the nature of the underlying disease).
- 13. The participant is willing to give information relating to current drugs/therapies used to manage symptoms of their conditions, including restricted medications.
- 2a. Confirmed diagnosis of NPC disease based on: •The presence of biallelic pathogenic or likely pathogenic variants according to the American College of Medical Genetics and Genomics classification OR •One pathogenic or likely pathogenic variant and one variant of unknown significance, if clinical symptomatology is compatible with the disease and at least one disease biomarker (PPCS or C-triol) is over the normal laboratory range.
- 3. Newly-diagnosed and/or treatment-naïve patients that are unwilling or unable to take NPC-approved treatments (eg. miglustat)
- 4. Onset of neurological symptoms from 2 to 15 years.
- 5. Disability level at Baseline: Ataxic disturbances with a total SARA score of ≥3 and <30 at Baseline OR a functional SARA score of ≥1 and ≤12 at Baseline. Individuals with a total SARA score of ≥5 can enter the study automatically; inclusion of individuals with a total SARA score of 3 to 5 should be discussed with and approved by the Medical Monitor.
What rules you out
- 1. Any condition at Baseline that, in the opinion of the Principal Investigator, could interfere with study assessments (e.g., severe infection, severe cognitive impairment).
- 13. ECG with an average QTcF (corrected QT interval using Fridericia’s formula) interval of >450 msec for males and of >470 msec for females.
- For subprotocol AZA-001-301-GMx only: 14. Received migulstat in the 12 months prior to Baseline, unless •the dose was lower than the maximum dose specified in the miglustat Summary of Product Characteristics for patients with NPC disease, OR •the total duration of miglustat dosing was less than 12 months. Any participants receiving miglustat are required to undergo a 1-month washout period before starting study medication."
- 15. Known allergy to azasugars or any study drug excipient.
- 16. Evidence of suicidal ideation with intent (Type 4 to 5) on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening; this requirement is only applicable to participants judged by the Principal Investigator to be cognitively capable of understanding the concept of suicide.
- 2. A history of medical conditions other than NPC or GM1 or GM2 gangliosidosis that, in the opinion of the Principal Investigator, would confound scientific rigor or the interpretation of results.
- 4. The presence of another neurologic disease.
- 5. 5. The presence of moderate or severe hepatic impairment (alanine aminotransferase [ALT], aspartate aminotransferase [AST] and gamma-glutamyl transferase levels of >3x the upper limit of normal [ULN]).
- 12. A positive serum pregnancy test (for women of childbearing potential).
- 6. The presence of severe renal impairment (estimated glomerular filtration rate of <30 ml/min/1.73m2).
- 7. Total bilirubin of >2x ULN isolated bilirubin of >2x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%).
- 8. Platelet count of <100x109/L.
- 9. 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.
- 10. Prior use of an investigational drug within the 3 months prior to Screening, unless the product has since been approved and the participant is receiving a stable dose. Any patient previously determined to have late-onset disease, including for prior clinical trial or expanded access program participation, is not eligible for inclusion.
- 3.Body weight of <10 kg.
- For subprotocol AZA-001-301-NPC only: 14. Current treatment with miglustat, provided the patient • has been using the recommended dose as specified in the Summary of Product Characteristics for miglustat (see Appendix 4) 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.
- 11. Prior participation in a clinical study involving gene therapy or stem cell transplantation.
The study team makes the final eligibility decision.
Where it's taking place
- Argentina
- Australia
- Mexico
- United States
- Canada
- Brazil
- Switzerland
- Turkey
- India
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Argentina; Australia; Mexico; United States; Canada; Brazil and 4 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.