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

NCT06614894 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 24-LDRTC-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Sanfilippo Syndrome; MPS3

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  1\. Safety and tolerability as measured by number of Participants with at least one serious and at least one non-serious Treatment Emergent Adverse Events (TEAEs), assessed by CTCAE v4.0.

  From baseline to 52 weeks

Secondary Outcomes (12)

• Changes in physical examination from baseline in motor capabilities and disease state: Physician (Clinician) Global Impression of Change

  From baseline to 52 weeks

• Change from baseline in EQ-5D-5L™ or EQ-5D-Y™

  From baseline to 52 weeks

• Change from baseline in VABS-III age equivalent scores (AEqs)

  From baseline to 52 weeks

• Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III

  From baseline to 52 weeks

• Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III

  From baseline to 52 weeks

Study Arms (3)

Ambroxol Hydrochloride 30mg - 9mg/kg/day

EXPERIMENTAL

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

Drug: Ambroxol Hydrochloride 30 mg tablet - 9 mg/kg/day

Ambroxol Hydrochloride 30mg - 18mg/kg/day

EXPERIMENTAL

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

Drug: Ambroxol Hydrochloride 30 mg tablet - 18 mg/kg/day

Ambroxol Hydrochloride 30mg - 27mg/kg/day

EXPERIMENTAL

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

Drug: Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/day

Interventions

Ambroxol Hydrochloride 30 mg tablet - 9 mg/kg/day DRUG

Ambroxol Hydrochloride 30 mg oral pill/tablet - 9 mg/kg/day

Also known as: Ambroxol

Ambroxol Hydrochloride 30mg - 9mg/kg/day

Ambroxol Hydrochloride 30 mg tablet - 18 mg/kg/day DRUG

Ambroxol Hydrochloride 30 mg oral pill/tablet - 18 mg/kg/day

Also known as: Ambroxol

Ambroxol Hydrochloride 30mg - 18mg/kg/day

Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/day DRUG

Ambroxol Hydrochloride 30 mg oral pill/tablet - 27 mg/kg/day

Also known as: Ambroxol

Ambroxol Hydrochloride 30mg - 27mg/kg/day

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• IRB - approved informed consent/assent signed by subject and/or parent(s) or legal guardian(s).
• Genetically confirmed diagnosis of MPS III disease.
• 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.
• Male or female; eighteen years of age and older, who is able to take Ambroxol Hydrochloride orally.
• Negative urine pregnancy test at screening for female subjects with child-bearing potential.
• 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.

You may not qualify if:

• Unwilling or unable to follow protocol requirements as per principal investigator.
• Any serious or chronic medical illness, including significant cardiac or severe debilitating pulmonary disease.
• Poorly controlled seizures, defined as more than one seizure per day for the past 6 months.
• 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.
• Any medical condition that, in the opinion of the PI, would make the subject unsuitable to participate in the study.
• Inability to cooperate for clinical and safety data collection.
• Known hypersensitivity to Ambroxol or any of its excipients.
• Use of genistein or Miglustat within one week of starting screening.
• Evidence of hepatitis B or hepatitis C infection upon serological testing at screening.
• Currently participating in another clinical trial or has completed an interventional trial less than 2 weeks prior to screening visit.
• 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.

Sponsors & Collaborators

• Ozlem Goker-Alpan: lead
• Team Sanfilippo: collaborator

Study Sites (1)

Lysosomal & Rare Disorders Research & Treatment Center, Inc.

Fairfax, Virginia, 22030, United States

RECRUITING

MeSH Terms

Conditions

Mucopolysaccharidosis III

Interventions

Tablets; Ambroxol

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Bromhexine; Aniline Compounds; Amines; Organic Chemicals; Cyclohexylamines

Study Officials

• Ozlem Goker-Alpan, MD

  Lysosomal & Rare Disorders Research & Treatment Center, Inc.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arooj Agha

CONTACT

571-732-4575; aagha@ldrtc.org

Lauren Noll

CONTACT

571-732-4655; lnoll@ldrtc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A Non-randomized (single arm) clinical trial where all participants will receive the same experimental therapy and undergo the same dose escalation plan. All participants will be followed over time to observe their response related to safety and effectiveness.

Study Record Dates

• First Submitted: August 28, 2024
• First Posted: September 26, 2024
• Study Start: December 1, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: August 20, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)