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Extension of Study HGT-SAN-055 Evaluating Administration of rhHNS in Patients With Sanfilippo Syndrome Type A (MPS IIIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01299727
Recruitment Status : Terminated (Completion of follow-up period)
First Posted : February 18, 2011
Last Update Posted : August 1, 2019
Information provided by (Responsible Party):

Brief 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). 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).

Condition or disease Intervention/treatment Phase
Sanfilippo Syndrome Biological: rhHNS-10 mg Biological: rhHNS-45 mg Biological: rhHNS-90 mg Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 1, 2011
Actual Primary Completion Date : February 27, 2019
Actual Study Completion Date : February 27, 2019

Arm Intervention/treatment
Experimental: rhHNS-10 mg
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
Biological: rhHNS-10 mg
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
Other Name: Recombinant human heparan N-sulfatase

Experimental: rhHNS-45 mg
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
Biological: rhHNS-45 mg
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
Other Name: Recombinant human heparan N-sulfatase

Experimental: rhHNS-90 mg
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
Biological: rhHNS-90 mg
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
Other Name: Recombinant human heparan N-sulfatase

Primary Outcome Measures :
  1. Long-term safety [ Time Frame: 8 years ]
    Safety will be measured by adverse events (by type and severity), changes in clinical laboratory testing (serum chemistry including liver function tests, hematology, and urinalysis), electrocardiograms (ECG), cerebrospinal fluid (CSF) chemistries (including cell counts and inflammatory markers), and anti-rhHNS antibodies (in CSF and serum).

Secondary Outcome Measures :
  1. Standardized neurocognitive and behavioral assessments [ Time Frame: 8 years ]
    Sanfilippo-specific behavioral rating scales, gross and fine motor assessments, functional adaptive rating scales, quality of life questionnaires, and Children's Sleep Habits Rating Scale.

  2. Concentration of rhHNS in cerebrospinal fluid (CSF) and serum [ Time Frame: 8 years ]
  3. Concentration of inflammatory cytokines in serum and CSF [ Time Frame: 8 years ]
  4. Concentration of safety and potential surrogate efficacy biomarkers in CSF, urine, and serum. [ Time Frame: 8 years ]
  5. Concentration of heparan sulfate and heparan sulfate derivatives in urine, plasma and serum. [ Time Frame: 8 years ]
  6. Brain magnetic resonance imaging (MRI) and auditory brainstem response (ABR), aka Brainstem Auditory Evoked Potentials. [ Time Frame: 8 years ]
    To assess patients regional brain volume and the extent of hearing loss.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:Patients must meet all of the following criteria to be considered eligible for enrollment:

  1. The patient must have completed Study HGT SAN 055 and the opinion of the investigator, has no safety or medical issues that contraindicate participation.
  2. The patient, patient's parent(s), or legally authorized representative(s) has voluntarily signed an Institutional Review Board / Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient's, the patient's, patient's parents or legally authorized representative's consent and patient's assent, as appropriate, must be obtained prior to any study specific procedures.
  3. The patient has received at least 5 of the 6 planned infusions of rhHNS in the HGT-SAN-055 study.
  4. Patients must be medically stable, in the opinion of the Investigator, to accommodate the protocol requirements, including travel, assessments, and IDDD surgery (if necessary for replacement purposes), without placing an undue burden on the patient/patient's family.

Exclusion Criteria:

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:

  1. The patient has experienced an adverse reaction to study drug in Study HGT-SAN-55 that contraindicates further treatment with rhHNS.
  2. The patient has a known hypersensitivity to the active ingredient or any excipients in rhHNS drug product.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. The patient has a history of poorly controlled seizure disorder.
  8. 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.
  9. 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.
  10. 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).
  11. The patient has received a hematopoietic stem cell or bone marrow transplant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01299727

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Emma Children's Hospital, Academic Medical Center
Amsterdam, Netherlands
United Kingdom
St. Mary's Hospital
Manchester, United Kingdom
Sponsors and Collaborators
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Study Director: Study Director Shire

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Shire Identifier: NCT01299727    
Other Study ID Numbers: HGT-SAN-067
2010-021348-16 ( EudraCT Number )
First Posted: February 18, 2011    Key Record Dates
Last Update Posted: August 1, 2019
Last Verified: July 2019
Keywords provided by Shire:
Recombinant Human Heparan N-Sulfatase (rhHNS)
Sanfilippo Syndrome Type A (MPS IIIA)
Lysosomal storage disease (LSD)
Mucopolysaccharidosis (MPS) III
Additional relevant MeSH terms:
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Mucopolysaccharidosis III
Pathologic Processes
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases