Ambroxol for Sanfilippo Syndrome

Overseen By Lauren Noll

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ozlem Goker-Alpan

Must not be taking: CYP3A inducers/inhibitors

Disqualifiers: Cardiac disease, Pulmonary disease, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 2

Duration: 52 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

A dose escalation study to evaluate the safety, tolerability, and pharmacologic properties of Ambroxol in adult participants with Sanfilippo disease(s) (MPS3).

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that are strong inducers or inhibitors of CYP3A, as well as genistein or Miglustat, before starting the trial. If you are on these medications, you may need to switch to alternatives that do not interfere with the trial.

Is ambroxol generally safe for human use?

Ambroxol is generally considered safe and well-tolerated for treating respiratory diseases in both adults and children, with most side effects being mild and self-limiting. There is a low risk of severe skin reactions, and it has been used safely in various conditions, including prenatal care for respiratory distress syndrome. ^{1 2 3 4 5}

How does Ambroxol Hydrochloride differ from other drugs for Sanfilippo Syndrome?

Ambroxol Hydrochloride is unique for Sanfilippo Syndrome as it is primarily known for its use in respiratory conditions to help clear mucus, and there are no standard treatments specifically for Sanfilippo Syndrome. This makes its application in this context novel, as it may offer a new approach to managing symptoms of this rare genetic disorder. ^{6 7 8 9 10}

Research Team

Ozlem Goker-Alpan, MD

Principal Investigator

Lysosomal & Rare Disorders Research & Treatment Center, Inc.

Eligibility Criteria

This trial is for adults with Sanfilippo disease, also known as Mucopolysaccharidosis Type III (MPS III). Participants must be at least 18 years old. Specific inclusion and exclusion criteria are not listed but typically involve health status and history.

Inclusion Criteria

My genetic test shows specific mutations in SGSH, NAGLU, HGSNAT, or GNS genes.

IRB-approved informed consent/assent signed by subject and/or parent(s) or legal guardian(s)

Elevated excretion of urinary GAGs and/or serum HS (if no historical data is available, screening GAGs and serum HS values will be utilized to assess inclusion criteria)

Exclusion Criteria

I am able to participate in all required study activities.

I do not have any serious or long-term illnesses, including major heart or severe lung conditions.

I have had more than one seizure a day for the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive Ambroxol with dose escalation over 52 weeks, including regular assessments and safety monitoring

52 weeks

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Ambroxol Hydrochloride

Trial Overview The study tests three different doses of Ambroxol Hydrochloride tablets (9 mg/kg/day, 18 mg/kg/day, and 27 mg/kg/day) to see which dose is safe and works best in adults with MPS III.

Participant Groups

Group I: Ambroxol Hydrochloride 30mg - 9mg/kg/day Experimental Treatment 1 Intervention

Ambroxol Hydrochloride 30mg Dose escalation: Initial dose of 9mg/kg/day (or max dose 150mg TID)

Group II: Ambroxol Hydrochloride 30mg - 27mg/kg/day Experimental Treatment 1 Intervention

Ambroxol Hydrochloride 30mg Dose escalation: 27mg/kg/day (or max dose 1350mg QD)

Group III: Ambroxol Hydrochloride 30mg - 18mg/kg/day Experimental Treatment 1 Intervention

Ambroxol Hydrochloride 30mg Dose escalation: 18mg/kg/day (or max dose 300mg TID)

Who Is Running the Clinical Trial?

Ozlem Goker-Alpan

Lead Sponsor

Trials

1

Recruited

10+

Team Sanfilippo

Collaborator

Trials

2

Recruited

20+

References

1. England pubmed.ncbi.nlm.nih.gov

Safety of ambroxol in the treatment of airway diseases in adult patients. [2019]

2. Australia pubmed.ncbi.nlm.nih.gov

Antenatal use of ambroxol for the prevention of infant respiratory distress syndrome. [2019]

3. Italy pubmed.ncbi.nlm.nih.gov

An overview of efficacy and safety of ambroxol for the treatment of acute and chronic respiratory diseases with a special regard to children. [2023]

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

Prevention of respiratory distress syndrome in preterm infants by antenatal ambroxol: a meta-analysis of randomized controlled trials. [2013]

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

Ambroxol for prevention and treatment of hyaline membrane disease. [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Dapsone as an alternative therapy in children with familial mediterranean Fever. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Dramatic beneficial effect of interleukin-1 inhibitor treatment in patients with familial Mediterranean fever complicated with amyloidosis and renal failure. [2012]

8. England pubmed.ncbi.nlm.nih.gov

Interventions for reducing inflammation in familial Mediterranean fever. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

[Evidence-based treatment recommendations for familial Mediterranean fever : A joint statement by the Society for Pediatric and Adolescent Rheumatology and the German Society for Rheumatology]. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Canakinumab for the treatment of adult-onset Still's disease. [2021]