Sanfilippo SyndromePhase 1/2NCT01299727
Extension of Study HGT-SAN-055 Evaluating Administration of rhHNS in Patients With Sanfilippo Syndrome Type A (MPS IIIA)
A Phase 1/2 study testing rhHNS-10 mg, rhHNS-45 mg and rhHNS-90 mg in people with Sanfilippo Syndrome, run by Shire at 2 sites in 2 countries.
Trial summary
Sanfilippo syndrome, or Mucopolysaccharidosis (MPS) III, is a rare lysosomal storage disease (LSD) caused by loss in activity of 1 of 9 enzymes necessary for degradation of the glycosaminoglycan (GAG) heparan sulfate (HS) in lysosomes. MPS IIIA results from deficiency of the enzyme heparan N-sulfatase (sulfamidase). Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Sanfilippo Syndrome
- What is being tested?
- rhHNS-10 mg, rhHNS-45 mg and rhHNS-90 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Mar 2011to 12 Apr 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Subjects will be excluded from the study if there is evidence of any of the following criteria at screening or at anytime during the study:
- The patient has experienced an adverse reaction to study drug in Study HGT-SAN-55 that contraindicates further treatment with rhHNS.
- The patient has a known hypersensitivity to the active ingredient or any excipients in rhHNS drug product.
- The patient has significant non-MPS IIIA related central nervous system (CNS) impairment or behavioral disturbances that would confound the scientific integrity or interpretation of study assessments, as determined by the Investigator.
- The patient has significant MPS IIIA behavioral-related issues, as determined by the Investigator, which would preclude performance of study neurocognitive and developmental testing procedures.
- The patient is pregnant, breast feeding, or is a female patient of childbearing potential, who will not or cannot comply with the use of an acceptable method of birth control, such as condoms, barrier method, oral contraception, etc.
Show all 12Show fewer
- The patient has any known or suspected hypersensitivity to anesthesia or is thought to have an unacceptably high risk for anesthesia due to airway compromise or other conditions.
- The patient has a history of poorly controlled seizure disorder.
- The patient is currently receiving psychotropic or other medications, which in the Investigator's opinion, would be likely to substantially confound test results and the dose and regimen of which cannot be kept constant throughout the study.
- The patient cannot sustain absence from aspirin, non-steroidal medications, or medications that affect blood clotting within 1 week prior to a relevant study-related procedure (eg, device re-implantation if applicable), or has ingested such medications within 1 week before any procedures in which any change in clotting activity would be deleterious.
- The patient has received treatment with any investigational drug (other than rhHNS) intended as a treatment for MPS IIIA within the 30 days prior to, or during the study, or is currently enrolled in another study that involves an investigational drug or device (screening through safety follow-up contact).
- The patient has received a hematopoietic stem cell or bone marrow transplant.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Netherlands1 site
Emma Children's Hospital, Academic Medical Center
Amsterdam
About this study
Official title: An Open-Label Extension of Study HGT-SAN-055 Evaluating Long Term Safety and Clinical Outcomes of Intrathecal Administration of rhHNS in Patients With Sanfilippo Syndrome Type A (MPS IIIA)
Sanfilippo syndrome, or Mucopolysaccharidosis (MPS) III, is a rare lysosomal storage disease (LSD) caused by loss in activity of 1 of 9 enzymes necessary for degradation of the glycosaminoglycan (GAG) heparan sulfate (HS) in lysosomes. MPS IIIA results from deficiency of the enzyme heparan N-sulfatase (sulfamidase). In the absence of this enzyme, intermediates of the HS degradation process accumulate in the lysosomes of neurons and glial cells, with lesser accumulation outside the brain. MPS IIIA symptoms arise on average at 7 months of age, with the average age of diagnosis at 4.5 years for the majority of patients. Patients present a wide spectrum and severity of clinical symptoms. The central nervous system (CNS) is the most severely affected organ system in patients with MPS IIIA, evidenced by deficits in language development, motor skills, and intellectual development. In addition, there are abnormal behaviors including but not limited to aggression and excess motor activity/hyperactivity that contribute to disturbances in sleep.Overall, individuals with MPS IIIA have a marked developmental delay and significantly reduced lifespan to 15 years of age on average.
The purpose of this study is to collect long term safety and tolerability data in patients with MPS IIIA who previously received rhHNS in study HGT-SAN-055 (NCT01155778).
Read the detailed description
No effective, disease-modifying therapies are currently approved as treatments for this devastating and disabling disease.
Shire Human Genetic Therapies (Shire HGT) is developing a sulfamidase enzyme replacement therapy (ERT)rhHNS for patients with MPS IIIA. rhHNS is being administered into the cerebrospinal fluid (CSF) via an surgically implanted intrathecal drug delivery device (IDDD), because when administered intravenously (IV) it does not cross the blood brain barrier (BBB).
This is a multicenter study designed to collect long-term safety and tolerability data in patients with Sanfilippo Syndrome Type A (MPS IIIA) who received rhHNS via a surgically implanted intrathecal drug delivery device (IDDD) in study HGT-SAN-055 and elected to continue therapy.Patients will continue in the treatment group as they participated in the HGT-SAN-055 study (rhHNS administered by IT injection 10 mg once per month, 45 mg once per month or 90 mg once per month.
The study duration will be a maximum duration of 8 years of rhHNS treatment or until rhHNS is commercially available, the patient discontinues from the study, the Sponsor stops the study, or the Sponsor discontinues the development of rhHNS.
- Conditions
- Sanfilippo Syndrome
- Being tested
- rhHNS-10 mg, rhHNS-45 mg, rhHNS-90 mg
- Keywords
- Recombinant Human Heparan N-Sulfatase (rhHNS), Sanfilippo Syndrome Type A (MPS IIIA), Lysosomal storage disease (LSD), Mucopolysaccharidosis (MPS) III
- Medical subject headings
- Mucopolysaccharidosis III, Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhHNS-10 mgBiological
Also called Recombinant human heparan N-sulfatase
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
rhHNS-45 mgBiological
Also called Recombinant human heparan N-sulfatase
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
rhHNS-90 mgBiological
Also called Recombinant human heparan N-sulfatase
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
| Study group | Role | What they receive |
|---|---|---|
| rhHNS-10 mg | Experimental | Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years Receives: Biological: rhHNS-10 mg |
| rhHNS-45 mg | Experimental | Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years Receives: Biological: rhHNS-45 mg |
| rhHNS-90 mg | Experimental | Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years Receives: Biological: rhHNS-90 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered study drug related. Treatment-emergent Adverse events (TEAEs) were defined as all adverse events (AEs) from the time of the surgery for first IDDD implantation or first dose of HGT-1410 in study HGT-SAN-055 (NCT01155778) to the data cutoff date, or 30 days after the date of the last dose or 2 weeks after the date of device explant if early termination occurred. TEAEs included participants with any AE, any drug-related AE, any surgery-related AE, any IDDD-related AE, and any IT administration process-related AE, any SAE, any serious drug-related AE.
Measured: From start of study drug administration up to follow-up (Month 103)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity
An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered study drug related. TEAEs were defined as all AEs from the time of the surgery for first IDDD implantation or first dose of HGT-1410 in study HGT-SAN-055 (NCT01155778) to the data cutoff date, or 30 days after the date of the last dose or 2 weeks after the date of device explant if early termination occurred. Severity of an AE is determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities; Severe: Inability to carry out usual activities.
Measured: From start of study drug administration up to follow-up (Month 103)
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Clinical laboratory assessments include hematology, serum chemistry including liver function tests, coagulation urinalysis and cerebrospinal fluid (CSF) were reported.
Measured: From start of study drug administration up to follow-up (Month 103)
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs)
Any change in ECG assessments which were deemed to be clinically significant findings and abnormalities were recorded as TEAEs.
Measured: From start of study drug administration up to follow-up (Month 103)
Number of Participants With Postive Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS)
Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive Anti-rhHNS antibody status in serum were reported.
Measured: Month 103
Number of Participants With Positive Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS)
Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive anti-rhHNS antibody in CSF were reported
Measured: Month 103
Secondary outcomes (7)
Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103
BSID-III was used to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers aged 0-42 months and consisted of a series of developmental play tasks. Score ranges: Cognitive scale 0-91, Receptive communication 0-49, Expressive communication 0-48, Fine motor 0-66 and Gross motor 0-72. Higher values denote stronger skills and abilities in the domain, indicating better outcomes.
Measured: Baseline, Month 103
Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III)/Kaufman Assessment Battery for Children Second Edition (KABC-II) Age-Equivalent Scores at Month 103
BSID-III was used to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers aged 0-42 months and consisted of a series of developmental play tasks. KABC-II was an individually administered measure of the processing and reasoning abilities of children and adolescents between the ages of 3 and 18 years and an alternative to BSID-III. Raw scores were converted to age--equivalent scores to measure ability, skill, and knowledge, expressed as the age at which most individuals reach the same level (age norm; range: 0, unbound ). A positive value indicates improvement. The BSID--III and KABC--II age--equivalent scores were based on the cognitive domain and average non-verbal age-equivalent score, respectively.
Measured: Baseline, Month 103
Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID-III) and Kaufman Assessment Battery for Children Second Edition (KABC-II) at Month 103
BSID-III was used to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers aged 0-42 months and consisted of a series of developmental play tasks. KABC-II was an individually administered measure of the processing and reasoning abilities of children and adolescents between the ages of 3 and 18 years and an alternative to BSID-III. Raw scores of successfully completed items are converted to scale scores and to composite scores. The mean composite score is 100 and the standard deviation (SD) is 15. The DQ was a means to express a neurodevelopmental/cognitive delay which was computed as a ratio and expressed as a percentage using the age equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0-100). A positive value indicates improvement in health and cognition.
Measured: Baseline, Month 103
Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103
VABS-II measured adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It was an instrument that supports the diagnosis of intellectual and developmental disabilities in participants. This test measured 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other four domains). Scoring is 'Usually' = 2, 'Sometimes'/Partially' = 1 or 'Never' = 0. The standard scores represent a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability. A positive change value indicates improvement in adaptive functioning, communication, daily living skills, socialization and motor skills domains were reported here. The range for individual standard scores is 20-160.
Measured: Baseline, Month 103
Change From Baseline in Cerebrospinal Fluid (CSF) Total Heparan Sulfate Levels at Month 103
Change from baseline in CSF total heparan sulfate at month 103 was recorded.
Measured: Baseline, Month 103
Change From Baseline in Urine Glycosaminoglycan (GAG) Levels at Month 103
Change from baseline in Urine GAG at month 103 was recorded.
Measured: Baseline, Month 103
Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103
Brain MRI parameters include grey matter volume (GMV), white matter volume (WMV) and Intracranial cerebrospinal fluid Volume (ICSFV). Change from baseline in brain MRI at Month 103 was reported.
Measured: Baseline, Month 103
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2011 (estimated)
- Study start1 Mar 2011
- Primary completion12 Apr 2019
- Study completion12 Apr 2019
Why it stopped: Completion of follow-up period
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01299727
- Sponsor's protocol ID
- HGT-SAN-067
- Other IDs
- 2010-021348-16
- Status last verified
- May 2021
- First submitted
- 16 Feb 2011
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Wijburg FA, Heap F, Rust S, de Ruijter J, Tump E, Marchal JP, Nestrasil I, Shapiro E, Jones SA, Alexanderian D. Long-term safety and clinical outcomes of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A. Mol Genet Metab. 2021 Dec;134(4):317-322. doi: 10.1016/j.ymgme.2021.09.003. Epub 2021 Sep 14.
PubMed 34600820King B, Marshall N, Beard H, Hassiotis S, Trim PJ, Snel MF, Rozaklis T, Jolly RD, Hopwood JJ, Hemsley KM. Evaluation of enzyme dose and dose-frequency in ameliorating substrate accumulation in MPS IIIA Huntaway dog brain. J Inherit Metab Dis. 2015 Mar;38(2):341-50. doi: 10.1007/s10545-014-9790-8. Epub 2014 Nov 25.
PubMed 25421091Langford-Smith A, Wilkinson FL, Langford-Smith KJ, Holley RJ, Sergijenko A, Howe SJ, Bennett WR, Jones SA, Wraith J, Merry CL, Wynn RF, Bigger BW. Hematopoietic stem cell and gene therapy corrects primary neuropathology and behavior in mucopolysaccharidosis IIIA mice. Mol Ther. 2012 Aug;20(8):1610-21. doi: 10.1038/mt.2012.82. Epub 2012 May 1.
PubMed 22547151
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension of Study HGT-SAN-055 Evaluating Long Term Safety and Clinical Outcomes of Intrathecal Administration of rhHNS in Patients With Sanfilippo Syndrome Type A (MPS IIIA)
- ClinicalTrials.gov ID
- NCT01299727
- Acronym / sponsor ID
- HGT-SAN-067
- Conditions
- Sanfilippo Syndrome
- Keywords
- Recombinant Human Heparan N-Sulfatase (rhHNS), Sanfilippo Syndrome Type A (MPS IIIA), Lysosomal storage disease (LSD), Mucopolysaccharidosis (MPS) III
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Completion of follow-up period
- Enrolment
- 12 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 1 Mar 2011 (actual)
- Primary completion
- 12 Apr 2019 (actual)
- Study completion
- 12 Apr 2019 (actual)
- First posted
- 18 Feb 2011 (estimated)
- Results
- Posted 21 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sanfilippo syndrome, or Mucopolysaccharidosis (MPS) III, is a rare lysosomal storage disease (LSD) caused by loss in activity of 1 of 9 enzymes necessary for degradation of the glycosaminoglycan (GAG) heparan sulfate (HS) in lysosomes. MPS IIIA results from deficiency of the enzyme heparan N-sulfatase (sulfamidase). In the absence of this enzyme, intermediates of the HS degradation process accumulate in the lysosomes of neurons and glial cells, with lesser accumulation outside the brain. MPS IIIA symptoms arise on average at 7 months of age, with the average age of diagnosis at 4.5 years for the majority of patients. Patients present a wide spectrum and severity of clinical symptoms. The central nervous system (CNS) is the most severely affected organ system in patients with MPS IIIA, evidenced by deficits in language development, motor skills, and intellectual development. In addition, there are abnormal behaviors including but not limited to aggression and excess motor activity/hyperactivity that contribute to disturbances in sleep.Overall, individuals with MPS IIIA have a marked developmental delay and significantly reduced lifespan to 15 years of age on average.
The purpose of this study is to collect long term safety and tolerability data in patients with MPS IIIA who previously received rhHNS in study HGT-SAN-055 (NCT01155778).
Detailed description
No effective, disease-modifying therapies are currently approved as treatments for this devastating and disabling disease.
Shire Human Genetic Therapies (Shire HGT) is developing a sulfamidase enzyme replacement therapy (ERT)rhHNS for patients with MPS IIIA. rhHNS is being administered into the cerebrospinal fluid (CSF) via an surgically implanted intrathecal drug delivery device (IDDD), because when administered intravenously (IV) it does not cross the blood brain barrier (BBB).
This is a multicenter study designed to collect long-term safety and tolerability data in patients with Sanfilippo Syndrome Type A (MPS IIIA) who received rhHNS via a surgically implanted intrathecal drug delivery device (IDDD) in study HGT-SAN-055 and elected to continue therapy.Patients will continue in the treatment group as they participated in the HGT-SAN-055 study (rhHNS administered by IT injection 10 mg once per month, 45 mg once per month or 90 mg once per month.
The study duration will be a maximum duration of 8 years of rhHNS treatment or until rhHNS is commercially available, the patient discontinues from the study, the Sponsor stops the study, or the Sponsor discontinues the development of rhHNS.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| rhHNS-10 mg | Experimental | Biological: rhHNS-10 mgOnce per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years |
| rhHNS-45 mg | Experimental | Biological: rhHNS-45 mgOnce per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years |
| rhHNS-90 mg | Experimental | Biological: rhHNS-90 mgOnce per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (12 listed)
- Subjects will be excluded from the study if there is evidence of any of the following criteria at screening or at anytime during the study:
- The patient has experienced an adverse reaction to study drug in Study HGT-SAN-55 that contraindicates further treatment with rhHNS.
- The patient has a known hypersensitivity to the active ingredient or any excipients in rhHNS drug product.
- The patient has significant non-MPS IIIA related central nervous system (CNS) impairment or behavioral disturbances that would confound the scientific integrity or interpretation of study assessments, as determined by the Investigator.
- The patient has significant MPS IIIA behavioral-related issues, as determined by the Investigator, which would preclude performance of study neurocognitive and developmental testing procedures.
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 |
|---|---|---|
| rhHNS-10 mgAlso: Recombinant human heparan N-sulfataseOnce per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years | Biological | rhHNS-10 mg |
| rhHNS-45 mgAlso: Recombinant human heparan N-sulfataseOnce per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years | Biological | rhHNS-45 mg |
| rhHNS-90 mgAlso: Recombinant human heparan N-sulfataseOnce per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years | Biological | rhHNS-90 mg |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From start of study drug administration up to follow-up (Month 103)
An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered study drug related. Treatment-emergent Adverse events (TEAEs) were defined as all adverse events (AEs) from the time of the surgery for first IDDD implantation or first dose of HGT-1410 in study HGT-SAN-055 (NCT01155778) to the data cutoff date, or 30 days after the date of the last dose or 2 weeks after the date of device explant if early termination occurred. TEAEs included participants with any AE, any drug-related AE, any surgery-related AE, any IDDD-related AE, and any IT administration process-related AE, any SAE, any serious drug-related AE.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity
Time frame: From start of study drug administration up to follow-up (Month 103)
An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered study drug related. TEAEs were defined as all AEs from the time of the surgery for first IDDD implantation or first dose of HGT-1410 in study HGT-SAN-055 (NCT01155778) to the data cutoff date, or 30 days after the date of the last dose or 2 weeks after the date of device explant if early termination occurred. Severity of an AE is determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities; Severe: Inability to carry out usual activities.
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Time frame: From start of study drug administration up to follow-up (Month 103)
Clinical laboratory assessments include hematology, serum chemistry including liver function tests, coagulation urinalysis and cerebrospinal fluid (CSF) were reported.
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs)
Time frame: From start of study drug administration up to follow-up (Month 103)
Any change in ECG assessments which were deemed to be clinically significant findings and abnormalities were recorded as TEAEs.
Number of Participants With Postive Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS)
Time frame: Month 103
Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive Anti-rhHNS antibody status in serum were reported.
Number of Participants With Positive Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS)
Time frame: Month 103
Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive anti-rhHNS antibody in CSF were reported
7 secondary outcomes
Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103
Time frame: Baseline, Month 103
Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III)/Kaufman Assessment Battery for Children Second Edition (KABC-II) Age-Equivalent Scores at Month 103
Time frame: Baseline, Month 103
Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID-III) and Kaufman Assessment Battery for Children Second Edition (KABC-II) at Month 103
Time frame: Baseline, Month 103
Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103
Time frame: Baseline, Month 103
Change From Baseline in Cerebrospinal Fluid (CSF) Total Heparan Sulfate Levels at Month 103
Time frame: Baseline, Month 103
Change From Baseline in Urine Glycosaminoglycan (GAG) Levels at Month 103
Time frame: Baseline, Month 103
Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103
Time frame: Baseline, Month 103
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34600820Wijburg FA, Heap F, Rust S, de Ruijter J, Tump E, Marchal JP, Nestrasil I, Shapiro E, Jones SA, Alexanderian D. Long-term safety and clinical outcomes of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A. Mol Genet Metab. 2021 Dec;134(4):317-322. doi: 10.1016/j.ymgme.2021.09.003. Epub 2021 Sep 14.
- Derived from this study: PubMed 25421091King B, Marshall N, Beard H, Hassiotis S, Trim PJ, Snel MF, Rozaklis T, Jolly RD, Hopwood JJ, Hemsley KM. Evaluation of enzyme dose and dose-frequency in ameliorating substrate accumulation in MPS IIIA Huntaway dog brain. J Inherit Metab Dis. 2015 Mar;38(2):341-50. doi: 10.1007/s10545-014-9790-8. Epub 2014 Nov 25.
- Derived from this study: PubMed 22547151Langford-Smith A, Wilkinson FL, Langford-Smith KJ, Holley RJ, Sergijenko A, Howe SJ, Bennett WR, Jones SA, Wraith J, Merry CL, Wynn RF, Bigger BW. Hematopoietic stem cell and gene therapy corrects primary neuropathology and behavior in mucopolysaccharidosis IIIA mice. Mol Ther. 2012 Aug;20(8):1610-21. doi: 10.1038/mt.2012.82. Epub 2012 May 1.
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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.
Study Director study director
Takeda
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rhHNS-10 mg, rhHNS-45 mg and rhHNS-90 mg in people with Sanfilippo Syndrome, run by Shire at 2 sites in 2 countries.
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 0 inclusion and 12 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: stopped early, as of the sponsor's last update on 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands, United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) (time frame: From start of study drug administration up to follow-up (Month 103)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01299727, which also lists 3 linked publications.
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 14 Jun 2021.