extension of study hgt-san-055 evaluating administration of rhhns in patients with sanfilippo syndrome type a (mps iiia)

Conditions: Sanfilippo Syndrome

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).

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.

Eligibility criteria:
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.

Keywords: recombinant human heparan n-sulfatase (rhhns) sanfilippo syndrome type a (mps iiia) lysosomal storage disease (lsd) mucopolysaccharidosis (mps) iii