Sanfilippo SyndromePhase 2/3NCT06614894
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
A Phase 2/3 study testing Ambroxol Hydrochloride 30 mg tablet - 9 mg/kg/day, Ambroxol Hydrochloride 30 mg tablet - 18 mg/kg/day and Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/day in people with Sanfilippo Syndrome and MPS3, run by Ozlem Goker-Alpan at 1 site in United States.
Trial summary
A dose escalation study to evaluate the safety, tolerability, and pharmacologic properties of Ambroxol in adult participants with Sanfilippo disease(s) (MPS3). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Sanfilippo Syndrome, MPS3
- What is being tested?
- Ambroxol Hydrochloride 30 mg tablet - 9 mg/kg/day, Ambroxol Hydrochloride 30 mg tablet - 18 mg/kg/day and Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/day
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2024to 30 Jun 2026
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Lysosomal & Rare Disorders Research & Treatment Center, Inc.
Fairfax, Virginia, 22030
Arooj Agha, 571-732-4575, aagha@ldrtc.org
Lauren Noll, 571-732-4655, lnoll@ldrtc.org
About this study
A dose escalation study to evaluate the safety, tolerability, and pharmacologic properties of Ambroxol in adult participants with Sanfilippo disease(s) (MPS3).
Read the detailed description
This is a dose escalation study in which open label Ambroxol 30mg (study drug) will be administered to adult patients with Sanfilippo Disease (MPS3). Administration route of study drug will be either crushed and mixed with soft foods or as an Ambroxol suspension through a feeding tube, if applicable.
Study Timeline - Screening: 4 weeks (28 days) Treatment Period: 52 weeks Post-Treatment (after Week 52): 4 weeks withdrawal/safety follow-up period
Patients will be screened at which point a thorough review of the Informed Consent form will be completed, sNFL levels, urinary GAGs, and serum HS results/data from the previous 12 months will be reviewed, urine and blood will be collected, complete questionnaires, Motor skills assessments, and evaluation by the Principal Investigator (PI).
Eligible patients will proceed to receive the initial Ambroxol dose of 9mg/kg/day (maximum dose of 150 mg TID) divided into three equal doses per day, on-site. Other assessments including blood and urine collection, ECG, motor skills assessments, hearing test, questionnaires, and evaluation by the PI will be completed.
Following the first day of dosing, a virtual visit will be performed via Telemedicine within 1 week of dose start to assess safety.
At Weeks 12 and 24, enrolled patients will return to site for Ambroxol dose escalation to 18mg/kg/day (max dose of 300 mg TID) and 27mg/kg/day (max dose of 1350 mg/day), respectively. Assessments including blood and urine collection, ECG, motor skills assessments, hearing test, questionnaires, and evaluation by the PI will be completed at these visits.
Telemedicine visits will take place at Weeks 13 and 25, to assess safety.
At Week 36, a safety visit will be performed in which blood and urine will be collected.
At Week 52, end of study assessments will be completed which includes blood and urine collection, motor skills assessments, hearing test questionnaires, and evaluation by the PI will be conducted and treatment will be stopped.
A safety follow-up visit will be done 4 weeks after Week 52 visit is completed in which the patient will be evaluated by the PI.
- Conditions
- Sanfilippo Syndrome, MPS3
- Being tested
- Ambroxol Hydrochloride 30 mg tablet - 9 mg/kg/day, Ambroxol Hydrochloride 30 mg tablet - 18 mg/kg/day, Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/day
- Medical subject headings
- Mucopolysaccharidosis III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ambroxol Hydrochloride 30 mg tablet - 9 mg/kg/dayDrug
Also called Ambroxol
Ambroxol Hydrochloride 30 mg oral pill/tablet - 9 mg/kg/day
Ambroxol Hydrochloride 30 mg tablet - 18 mg/kg/dayDrug
Also called Ambroxol
Ambroxol Hydrochloride 30 mg oral pill/tablet - 18 mg/kg/day
Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/dayDrug
Also called Ambroxol
Ambroxol Hydrochloride 30 mg oral pill/tablet - 27 mg/kg/day
| Study group | Role | What they receive |
|---|---|---|
| Ambroxol Hydrochloride 30mg - 9mg/kg/day | Experimental | Ambroxol Hydrochloride 30mg Dose escalation: Initial dose of 9mg/kg/day (or max dose 150mg TID) Receives: 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) Receives: 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) Receives: Drug: Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
- 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.
Measured: 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
Physician (Clinician) Global Impression of Change (scale: 0-very much worse - 7-Very much improved).
Measured: From baseline to 52 weeks
Change from baseline in EQ-5D-5L™ or EQ-5D-Y™
Change from baseline in EQ-5D-5L™ or EQ-5D-Y™
Measured: From baseline to 52 weeks
Change from baseline in VABS-III age equivalent scores (AEqs)
Vineland Adaptive Behavior scale-III
Measured: From baseline to 52 weeks
Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III
Plasma PK parameter estimates for oral Ambroxol include the area under the curve (AUC).
Measured: From baseline to 52 weeks
Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III
Plasma PK parameter estimates for oral Ambroxol include maximum concentration (Cmax).
Measured: From baseline to 52 weeks
Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III
Plasma PK parameter estimates for oral Ambroxol include time to maximum dose concentration (Tmax).
Measured: From baseline to 52 weeks
Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III
Plasma PK parameter estimates for oral Ambroxol include terminal half-life (t1/2).
Measured: From baseline to 52 weeks
Assessment of Pharmacodynamics of Ambroxol in subjects with MPS III
Changes from baseline in Urinary GAG levels as measured by total quantified concentration. Changes from baseline will be analyzed using main effects, fixed for treatment (dose), categorical visit number, treatment-by-visit interaction, baseline value as covariate, and subject as the random effect.
Measured: From baseline to 52 weeks
Assessment of Pharmacodynamics of Ambroxol in subjects with MPS III
Serum Heparan sulfate (HS) level changes from baseline as measured by total quantified concentration. Changes from baseline will be analyzed using main effects, fixed for treatment (dose), categorical visit number, treatment-by-visit interaction, baseline value as covariate, and subject as the random effect.
Measured: From baseline to 52 weeks
Change from baseline in Timed up and go (TUG) test
Change from baseline in Timed up and go (TUG) test and in ABR at Week 52 may also be tested for correlations.
Measured: From baseline to 52 weeks
Change from baseline in 10-meter walk test
Change from baseline in 10-meter walk test, may also be tested for correlations.
Measured: From baseline to 52 weeks
Change from baseline in SBRS
Change from baseline in SBRS
Measured: From baseline to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2024
- Study start1 Dec 2024
- Primary completion1 May 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sanfilippo SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ozlem Goker-Alpan
- Sponsor type
- University, hospital or other
- Collaborators
- Team Sanfilippo
- Responsible party
- Sponsor-investigator, Ozlem Goker-Alpan, Lysosomal and Rare Disorders Research and Treatment Center, Inc.
- Investigators
- Ozlem Goker-Alpan, MD, Principal investigator, Lysosomal & Rare Disorders Research & Treatment Center, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06614894
- Sponsor's protocol ID
- 24-LDRTC-01
- Status last verified
- Sep 2024
- First submitted
- 28 Aug 2024
- Last updated
- 20 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06614894
- Acronym / sponsor ID
- 24-LDRTC-01
- Conditions
- Sanfilippo Syndrome, MPS3
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Ozlem Goker-AlpanUniversity, hospital or other
- Collaborators
- Team Sanfilippo
- Study start
- 1 Dec 2024 (actual)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 26 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A dose escalation study to evaluate the safety, tolerability, and pharmacologic properties of Ambroxol in adult participants with Sanfilippo disease(s) (MPS3).
Detailed description
This is a dose escalation study in which open label Ambroxol 30mg (study drug) will be administered to adult patients with Sanfilippo Disease (MPS3). Administration route of study drug will be either crushed and mixed with soft foods or as an Ambroxol suspension through a feeding tube, if applicable.
Study Timeline - Screening: 4 weeks (28 days) Treatment Period: 52 weeks Post-Treatment (after Week 52): 4 weeks withdrawal/safety follow-up period
Patients will be screened at which point a thorough review of the Informed Consent form will be completed, sNFL levels, urinary GAGs, and serum HS results/data from the previous 12 months will be reviewed, urine and blood will be collected, complete questionnaires, Motor skills assessments, and evaluation by the Principal Investigator (PI).
Eligible patients will proceed to receive the initial Ambroxol dose of 9mg/kg/day (maximum dose of 150 mg TID) divided into three equal doses per day, on-site. Other assessments including blood and urine collection, ECG, motor skills assessments, hearing test, questionnaires, and evaluation by the PI will be completed.
Following the first day of dosing, a virtual visit will be performed via Telemedicine within 1 week of dose start to assess safety.
At Weeks 12 and 24, enrolled patients will return to site for Ambroxol dose escalation to 18mg/kg/day (max dose of 300 mg TID) and 27mg/kg/day (max dose of 1350 mg/day), respectively. Assessments including blood and urine collection, ECG, motor skills assessments, hearing test, questionnaires, and evaluation by the PI will be completed at these visits.
Telemedicine visits will take place at Weeks 13 and 25, to assess safety.
At Week 36, a safety visit will be performed in which blood and urine will be collected.
At Week 52, end of study assessments will be completed which includes blood and urine collection, motor skills assessments, hearing test questionnaires, and evaluation by the PI will be conducted and treatment will be stopped.
A safety follow-up visit will be done 4 weeks after Week 52 visit is completed in which the patient will be evaluated by the PI.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Ambroxol Hydrochloride 30mg - 9mg/kg/day | Experimental | Drug: Ambroxol Hydrochloride 30 mg tablet - 9 mg/kg/dayAmbroxol Hydrochloride 30mg Dose escalation: Initial dose of 9mg/kg/day (or max dose 150mg TID) |
| Ambroxol Hydrochloride 30mg - 18mg/kg/day | Experimental | Drug: Ambroxol Hydrochloride 30 mg tablet - 18 mg/kg/dayAmbroxol Hydrochloride 30mg Dose escalation: 18mg/kg/day (or max dose 300mg TID) |
| Ambroxol Hydrochloride 30mg - 27mg/kg/day | Experimental | Drug: Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/dayAmbroxol Hydrochloride 30mg Dose escalation: 27mg/kg/day (or max dose 1350mg QD) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
- Male or female; eighteen years of age and older, who is able to take Ambroxol Hydrochloride orally.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ambroxol Hydrochloride 30 mg tablet - 9 mg/kg/dayAlso: AmbroxolAmbroxol Hydrochloride 30 mg oral pill/tablet - 9 mg/kg/day | Drug | Ambroxol Hydrochloride 30mg - 9mg/kg/day |
| Ambroxol Hydrochloride 30 mg tablet - 18 mg/kg/dayAlso: AmbroxolAmbroxol Hydrochloride 30 mg oral pill/tablet - 18 mg/kg/day | Drug | Ambroxol Hydrochloride 30mg - 18mg/kg/day |
| Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/dayAlso: AmbroxolAmbroxol Hydrochloride 30 mg oral pill/tablet - 27 mg/kg/day | Drug | Ambroxol Hydrochloride 30mg - 27mg/kg/day |
Primary outcome
Safety and Tolerability
Time frame: From baseline to 52 weeks
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.
12 secondary outcomes
Changes in physical examination from baseline in motor capabilities and disease state: Physician (Clinician) Global Impression of Change
Time frame: From baseline to 52 weeks
Change from baseline in EQ-5D-5L™ or EQ-5D-Y™
Time frame: From baseline to 52 weeks
Change from baseline in VABS-III age equivalent scores (AEqs)
Time frame: From baseline to 52 weeks
Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III
Time frame: From baseline to 52 weeks
Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III
Time frame: From baseline to 52 weeks
Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III
Time frame: From baseline to 52 weeks
Assessment of Pharmacokinetics of Ambroxol in subjects with MPS III
Time frame: From baseline to 52 weeks
Assessment of Pharmacodynamics of Ambroxol in subjects with MPS III
Time frame: From baseline to 52 weeks
Assessment of Pharmacodynamics of Ambroxol in subjects with MPS III
Time frame: From baseline to 52 weeks
Change from baseline in Timed up and go (TUG) test
Time frame: From baseline to 52 weeks
Change from baseline in 10-meter walk test
Time frame: From baseline to 52 weeks
Change from baseline in SBRS
Time frame: From baseline to 52 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2025.
- Individual participant dataSharing planned: No
Related trials for Sanfilippo Syndrome
RecruitingPhase 1/2
Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
Mucopolysaccharidosis Type IIIA
Not yet recruitingObservational study
MPS IIIA Disease Monitoring Program
MPS IIIA, Sanfilippo Syndrome
Active, not recruitingPhase 1/2
An Open-label Phase I/II Study of JR-446 in Mucopolysaccharidosis Type IIIB
Mucopolysaccharidosis III-B
RecruitingPhase 2/3
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
MPS IIIA, Sanfilippo Syndrome
Not yet recruitingPhase 3
Intracerebroventricular Tralesinidase Alfa in Participants With MPS IIIB (Sanfilippo Syndrome Type B)
MPS IIIB
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ozlem Goker-Alpan, MD principal investigator
Lysosomal & Rare Disorders Research & Treatment Center, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ambroxol Hydrochloride 30 mg tablet - 9 mg/kg/day, Ambroxol Hydrochloride 30 mg tablet - 18 mg/kg/day and Ambroxol Hydrochloride 30 mg tablet - 27 mg/kg/day in people with Sanfilippo Syndrome and MPS3, run by Ozlem Goker-Alpan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Arooj Agha (571-732-4575, aagha@ldrtc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability (time frame: From baseline to 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2025.