Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of rhHNS Administration Via an IDDD in Pediatric Patients With Early Stage MPS IIIA Disease



Status:Active, not recruiting
Conditions:Other Indications
Therapuetic Areas:Other
Healthy:No
Age Range:Any
Updated:4/21/2016
Start Date:February 2014
End Date:May 2016

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A Randomized, Controlled, Open-label, Multicenter, Phase IIb Safety and Efficacy Study of rhHNS (Recombinant Human Heparan N Sulfatase) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Early Stage Mucopolysaccharidosis Type IIIA Disease

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.

No effective, disease-modifying therapies are currently approved as treatments for this
devastating and disabling disease.

Shire Human Genetic Therapies (Shire HGT) is developing an enzyme replacement therapy (ERT)
recombinant human heparan-N-sulfatase (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 study will evaluate the effect of 48 weeks of rhHNS treatment on the clinical course of
MPS IIIA, using cognitive function as the primary outcome measure. The trial will evaluate 2
dosing regimens of rhHNS administered via an IDDD in comparison with a no treatment control
group. Patients will be randomized 1:1:1 to either of the treatment groups or the no
treatment group. Treatment will be administered in an open-label manner. The safety and
tolerability profile of rhHNS will continue to be evaluated in this study.

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.
We found this trial at
4
sites
Chapel Hill, North Carolina 27599
(919) 962-2211
Univ of North Carolina Carolina’s vibrant people and programs attest to the University’s long-standing place...
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