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

Launched by OZLEM GOKER-ALPAN · Sep 25, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at a medication called Ambroxol Hydrochloride to see how safe it is and how well it works for adults with Sanfilippo Syndrome, also known as MPS III. The study will gradually increase the dosage of Ambroxol to find the right amount that is both safe and effective. It’s important to note that this trial is not yet recruiting participants, but when it begins, it will be open to adults aged 18 and older who have been genetically confirmed to have MPS III and meet specific health criteria.

To be eligible for the trial, participants must provide consent, have a specific genetic diagnosis related to MPS III, and be able to take Ambroxol by mouth. They should not have serious medical conditions or be taking certain medications that could interfere with the study. Participants will be asked to avoid grapefruit products for a few days before starting the treatment and throughout the study. If someone joins the trial, they can expect to help researchers learn more about this potential new treatment for Sanfilippo Syndrome.

Gender

ALL

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.