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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

ConditionsSanfilippo SyndromeMPS3
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18-99
SponsorOzlem Goker-Alpan

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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).

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

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

    Drug

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

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

    Drug

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

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

    Drug

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

Treatment groups

10 Participants
are divided into 3 treatment groups
Group A: Ambroxol Hydrochloride 30mg - 9mg/kg/dayExperimental treatment 1 intervention
Group B: Ambroxol Hydrochloride 30mg - 18mg/kg/dayExperimental treatment 1 intervention
Group C: Ambroxol Hydrochloride 30mg - 27mg/kg/dayExperimental treatment 1 intervention

Trial outcomes

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.

Time frame
From baseline to 52 weeks

Secondary outcomes

1

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

Physician (Clinician) Global Impression of Change (scale: 0-very much worse - 7-Very much improved).

Time frame
From baseline to 52 weeks
2

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

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

Time frame
From baseline to 52 weeks
3

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

Vineland Adaptive Behavior scale-III

Time frame
From baseline to 52 weeks
4

Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III

Plasma PK parameter estimates for oral Ambroxol include the area under the curve (AUC).

Time frame
From baseline to 52 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ozlem Goker-Alpan

Lead sponsor

Lysosomal and Rare Disorders Research and Treatment Center, Inc.

Sponsor institution

Team Sanfilippo

Collaborator

Source ClinicalTrials.gov
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