Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of rhHNS Administration Via an IDDD in Pediatric Patients With Early Stage MPS IIIA Disease
Condition: Sanfilippo Syndrome
MeSH terms: Mucopolysaccharidosis III; Syndrome
Intervention: Recombinant human heparan N-sulfatase [rhHNS]
Intervention description: Recombinant human heparan N-sulfatase [rhHNS]
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 12 Months
Maximum age: 48 Months
Healthy volunteers: No
Keywords: sulfoglucosamine sulfohydrolase (SGSH); recombinant human heparan N-sulfatase (rhHNS); Hunter's Syndrome; Shire HGT; Lysosomal Storage Disease (LSD); Sanfilippo Syndrome Type A (Sanfilippo A); enzyme replacement therapy (ERT)

Summary:

      Sanfilippo syndrome Type A, or Mucopolysaccharidosis (MPS) IIIA, is a rare lysosomal storage
      disease caused by deficiency of the enzyme heparan N-sulfatase (sulfamidase). In the absence
      of this enzyme, there is an accumulation of the glycosaminoglycan, heparan sulfate, resulting
      in progressive neurodegeneration. Symptoms are usually first noted in the 1st or 2nd year of
      life, although definitive diagnosis is often delayed, with an average age of diagnosis of 4.5
      years. The disease is characterized by developmental delays initially, followed by
      neurological developmental arrest, then regression. These developmental deficits are
      typically associated with severe behavioral disturbances. Patients have a significantly
      reduced lifespan, with few surviving beyond the 2nd or 3rd decade.

      The purpose of this study is to evaluate the safety and efficacy of recombinant human
      heparan-N-sulfatase (rhHNS) in pediatric patients with Early Stage Mucopolysaccharidosis Type
      III A Disease.
    

Eligibility criteria:

        Inclusion Criteria:

        Each patient must meet the following criteria to be enrolled in this study.

          1. Documented MPS IIIA diagnosis

          2. Age ≥12 months and ≤48 months

          3. The patient has a DQ score ≥60%

          4. The patient is medically stable, in the opinion of the Investigator, and able to
             accommodate the protocol requirements, including travel, assessments, and IDDD
             surgery, without placing an undue burden on the patient/patient's family

          5. The patient's parent(s) or legally authorized representative(s) must have voluntarily
             signed and dated an Independent Ethics Committee-approved informed consent form after
             all relevant aspects of the study have been explained and discussed with the patient's
             parent(s), or legally authorized representative(s). Consent of the patient's parent(s)
             or legally authorized representative(s) must be obtained prior to the start of any
             study procedures.

        Exclusion Criteria:

        Patients who meet any of the following criteria will be excluded from the study.

          1. The presence of significant non-MPS IIIA related CNS impairment or behavioral
             disturbances that would confound the scientific integrity or interpretation of study
             assessments, as determined by the Investigator.

          2. The presence of at least one S298P mutation in SGSH, associated with attenuated
             disease OR there is documentation of the S298P mutation in a sibling affected by MPS
             IIIA, provided parental consent is obtained to use this information.

          3. The presence of relatively attenuated MPS IIIA disease in an older sibling, defined as
             preservation of any speech beyond the age of 10 years.

          4. Visual or hearing impairment sufficient, in the clinical judgment of the investigator,
             to preclude cooperation with neurodevelopmental testing. Use of hearing aids is
             permitted.

          5. In the opinion of the Investigator, the patient is assessed as having an unacceptably
             high risk for anesthesia due to airway compromise, drug hypersensitivity, or other
             conditions (such as neuroleptic malignant syndrome, malignant hyperthermia, or other
             anesthesia-related concerns).

          6. The patient has a history of poorly controlled seizure disorder.

          7. The patient is currently receiving psychotropic or other medications, which in the
             Investigator's opinion would be likely to substantially confound test results.

          8. The patient has a history of bleeding disorder or is unable to abstain from
             medications that, in the opinion of the investigator, place them at risk of bleeding
             following surgery or LP.

          9. The patient participated in a clinical trial of another investigational medicinal
             product, within the 30 days prior to the study (or within 5 elimination half lives of
             the investigational product), or is currently enrolled in another study that involves
             an investigational drug or device. NOTE: Nutritional supplements, including genistein
             are permitted if they are taken or administered outside the context of a formal
             investigation.

         10. The patient has received a hematopoietic stem cell or bone marrow transplant, or gene
             therapy.

         11. The patient has a condition that is contraindicated as described in the SOPH-A-PORT
             Mini S-IDDD

         12. The patient's parent(s) or patient's legally authorized representative(s) is/are
             unable to understand the nature, scope, and possible consequences of the study, or
             do/does not agree to comply with the protocol defined schedule of assessments.

         13. The patient is unable to comply with the protocol (eg, has a clinically relevant
             medical condition making implementation of the protocol difficult, unstable social
             situation, or otherwise unlikely to complete the study) or is, in the opinion of the
             Investigator, otherwise unsuited for the study.

         14. The patient has any item (braces, tattoos, etc.) which would exclude the patient from
             being able to undergo MRI according to local Institutional Policy, or the patient has
             any other situation that would exclude the patient from undergoing any other procedure
             required in this study.