AZ-3102 for Tay-Sachs and Niemann-Pick Diseases

(RAINBOW Trial)

Recruiting at 3 trial locations

Overseen By Cécile Paquet-Luzy

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Azafaros A.G.

Must not be taking: Anti-epileptics, Azasugars

Disqualifiers: Inherited neurologic disease, Renal impairment, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests an oral medication called AZ-3102 in patients with GM2 Gangliosidosis and Niemann-Pick type C disease (NP-C). It aims to see if the drug is safe and how it works in their bodies.

Will I have to stop taking my current medications?

The trial requires that if you have been taking miglustat, it must be stopped at least 1 month before starting the study. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the treatment AZ-3102 for Tay-Sachs and Niemann-Pick Diseases?

Research on similar treatments shows that gene therapy using viral vectors can effectively deliver enzymes to the brain, reducing harmful substance buildup and improving symptoms in animal models of Niemann-Pick disease. Additionally, increasing the enzyme sialidase in Tay-Sachs cells has been shown to reduce harmful lipid accumulation, suggesting potential benefits for AZ-3102. ^{1 2 3 4 5}

Is AZ-3102 safe for humans?

Research on a similar treatment using adeno-associated viral vectors in non-human primates showed widespread expression in brain and spinal cord cells without signs of toxicity, suggesting it may be safe for humans. ^{2 3 4 5 6}

How is the drug AZ-3102 different from other treatments for Tay-Sachs and Niemann-Pick diseases?

AZ-3102 is unique because it may involve a novel approach using adeno-associated virus (AAV) to deliver acid sphingomyelinase (ASM) directly to the brain, potentially correcting the underlying enzyme deficiency in Niemann-Pick disease, which is not addressed by existing treatments. ^{2 3 7 8 9}

Eligibility Criteria

This trial is for 12-20 year olds with GM2 Gangliosidosis or Niemann-Pick type C disease. Participants need a confirmed diagnosis, and if they're sexually active, must follow contraceptive guidance. They can't have severe kidney issues, be pregnant/breastfeeding, or have taken certain drugs recently.

Inclusion Criteria

I have NP-C and haven't taken miglustat, or I stopped it due to side effects.

Total SARA score ≥ 1 at Baseline

Willing and able to complete protocol assessments

Exclusion Criteria

Platelet count < 100 x 10^9/L

Any abnormal conditions at baseline visit which, in the opinion of the PI, could interfere with study assessments (e.g., severe infection)

Positive serum pregnancy test at baseline for women of childbearing potential

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral administration of AZ-3102 or placebo for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Double-blind extension

Participants who complete the 12-week study may enter a double-blind extension period

Treatment Details

Interventions

• AZ-3102
• Placebo

Trial Overview The study tests the safety and effects of AZ-3102 (in two doses) compared to a placebo in patients over 12 weeks. It's randomized and double-blind, meaning neither doctors nor patients know who gets the real drug versus placebo.

Participant Groups

Group I: AZ-3102 (Dose 2) Experimental Treatment 1 Intervention

Participant will receive AZ-3102 (Dose 2) once daily during the course of the study (12 weeks) and the study extension (if applicable).

Group II: AZ-3102 (Dose 1) Experimental Treatment 1 Intervention

Participant will receive AZ-3102 (Dose 1) once daily during the course of the study (12 weeks) and the study extension (if applicable).

Group III: Placebo Placebo Group 1 Intervention

Participant will receive placebo once daily during the course of the study (12 weeks).

Who Is Running the Clinical Trial?

Azafaros A.G.

Lead Sponsor

Trials

2

Recruited

40+

References

1. United States pubmed.ncbi.nlm.nih.gov

Identification of novel biomarkers for Niemann-Pick disease using gene expression analysis of acid sphingomyelinase knockout mice. [2007]

2. United States pubmed.ncbi.nlm.nih.gov

Merits of combination cortical, subcortical, and cerebellar injections for the treatment of Niemann-Pick disease type A. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

AAV vector-mediated correction of brain pathology in a mouse model of Niemann-Pick A disease. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Adeno-associated viral vector serotype 9-based gene therapy for Niemann-Pick disease type A. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Sialidase-mediated depletion of GM2 ganglioside in Tay-Sachs neuroglia cells. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Therapeutic potential of intracerebroventricular replacement of modified human β-hexosaminidase B for GM2 gangliosidosis. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Intraparenchymal injections of acid sphingomyelinase results in regional correction of lysosomal storage pathology in the Niemann-Pick A mouse. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of N-Acetyl-l-Leucine in Children and Adults With GM2 Gangliosidoses. [2023]