High-dose ambroxol for adults with MPS III.

An Open Label Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacologic Properties of High Dose Ambroxol Hydrochloride in Adult (≥ 18 Years of Age) Subjects With MPS III

This study will try gradually higher oral doses of ambroxol to see if the medicine is safe and tolerated in adults with Sanfilippo syndrome (MPS III).

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Lysosomal and Rare Disorders Research and Treatment Center, Inc. (Academic / other)
• Locations: 1 site (Fairfax, Virginia)
• Trial ID: NCT06614894 on ClinicalTrials.gov

What this trial studies

This open-label dose-escalation study gives adult participants with genetically confirmed MPS III oral ambroxol starting at 9 mg/kg/day and increasing to 18 mg/kg/day and then 27 mg/kg/day over a 52-week treatment period. Participants are screened for eligibility, visit the Fairfax site for initial dosing and key assessments (blood, urine, ECG, motor skill tests, hearing, and questionnaires), and have a telemedicine safety check within one week after starting medication. Dose escalations occur on-site at weeks 12 and 24 and the study allows ambroxol to be taken crushed in soft food or as a suspension via feeding tube when needed, followed by a four-week post-treatment safety follow-up. Eligibility requires adults (≥18) with pathogenic SGSH, NAGLU, HGSNAT, or GNS variants and biochemical evidence of elevated urinary GAGs or serum heparan sulfate, and participants must avoid grapefruit during dosing.

Who should consider this trial

Good fit: Adults aged 18 or older with genetically confirmed MPS III types A–D, evidence of elevated urinary GAGs or serum heparan sulfate, ability to take oral ambroxol, and willingness to follow study restrictions (including avoiding grapefruit) are the ideal candidates.

Not a fit: People with MPS III type E, those under 18, individuals who cannot take oral medication, or those with contraindications to ambroxol or inability to attend the Fairfax site are unlikely to be eligible or benefit from participation.

Why it matters

Potential benefit: If tolerated and pharmacologically active, high-dose ambroxol could lower disease-related biochemical markers and potentially slow or improve clinical symptoms in adults with MPS III.

How similar studies have performed: Ambroxol has shown early, mixed signals in other lysosomal disorders but its use specifically for MPS III is relatively novel and not yet proven effective.

Eligibility criteria

Inclusion Criteria:

1. IRB - approved informed consent/assent signed by subject and/or parent(s) or legal guardian(s).
2. Genetically confirmed diagnosis of MPS III disease.
3. Genomic DNA analysis demonstrating a homozygous or compound heterozygous pathogenic variants in SGSH (type A), NAGLU (type B), HGSNAT (type C), or GNS (type D) genes. Type E will not be studied.
4. 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).
5. Male or female; eighteen years of age and older, who is able to take Ambroxol Hydrochloride orally.
6. Negative urine pregnancy test at screening for female subjects with child-bearing potential.
7. The subject is willing to abstain from consumption of grapefruit, grapefruit juice, or grapefruit containing products for 72 hours prior to administration of the first dose of Ambroxol and for the duration of the treatment period.

Exclusion Criteria:

1. Unwilling or unable to follow protocol requirements as per principal investigator.
2. Any serious or chronic medical illness, including significant cardiac or severe debilitating pulmonary disease.
3. Poorly controlled seizures, defined as more than one seizure per day for the past 6 months.
4. Medications identified as a strong inducers or inhibitors of CYP3A, and changing to another alternative drug to treat the condition would place the subject at undue risk.
5. Any medical condition that, in the opinion of the PI, would make the subject unsuitable to participate in the study.
6. Inability to cooperate for clinical and safety data collection.
7. Known hypersensitivity to Ambroxol or any of its excipients.
8. Use of genistein or Miglustat within one week of starting screening.
9. Evidence of hepatitis B or hepatitis C infection upon serological testing at screening.
10. Currently participating in another clinical trial or has completed an interventional trial less than 2 weeks prior to screening visit.
11. The subject has received strong inducers (Note: eg, herbal supplements) or inhibitors of CYP3A within 15 days or 5 half-lives from screening, whichever is longer, prior to enrollment. This also includes the consumption of grapefruit, grapefruit juice, or grapefruit containing products within 72 hours of starting Ambroxol administration.

Where this trial is running

Fairfax, Virginia

• Lysosomal & Rare Disorders Research & Treatment Center, Inc. — Fairfax, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Ozlem Goker-Alpan, MD — Lysosomal & Rare Disorders Research & Treatment Center, Inc.
• Study coordinator: Arooj Agha

Conditions Sanfilippo Syndrome; MPS3