A Phase I/II Safety, Tolerability, Ascending Dose and Dose Frequency Study of Recombinant Human Heparan-N-sulfatase (rhHNS) Intrathecal Administration via an Intrathecal Drug Delivery Device in Patients With Sanfilippo Syndrome Type A (MPS IIIA)

Phase 1

• Conditions: Sanfilippo Syndrome Type A or Mucopolysaccharidosis (MPS IIIA); MedDRA version: 14.0 Level: PT Classification code 10056890 Term: Mucopolysaccharidosis III System Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 14.0 Level: LLT Classification code 10056918 Term: Sanfilippo's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2009-015984-15-GB
• Lead Sponsor: Shire Human Genetic Therapies, Inc. (Shire HGT)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-03-17
• Study Completion: 2012-09-10
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 12

Inclusion Criteria

1.a.)Patients have a documented deficiency in sulfamidase enzyme activity of =10% of the lower limit of the normal range as measured in fibroblasts or leukocytes (based on measurements by a laboratory that is acceptable to Shire HGT).
AND EITHER b or C
b.)Patients have a normal enzyme activity level of at least 1 other sulfatase (to rule out multiple sulfatase deficiency) as measured in fibroblasts or leukocytes (based on measurements by a laboratory that is acceptable to Shire HGT).
c.) Patients have 2 documented mutations (based on assessments by a laboratory that is acceptable to Shire HGT).
2.The patient is =3 years of age and has a developmental age above 1 year (developmental age will be determined by the screening neurocognitive and developmental tests).
3.Patients must be medically stable, in the opinion of the Investigator, to accommodate the protocol requirements, including travel, assessments, and IDDD surgery, without placing an undue burden on the patient/patient's family.
4.The patient’s parent(s) or legal guardian must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.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.
2.The patient has MPS IIIA behavioral-related issues, as determined by the Investigator that would preclude performance of study neurocognitive and developmental testing procedures.
3.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
4. The patient is blind and/or deaf
5.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.
6.The patient or the patient's family has a history of neuroleptic malignant syndrome, malignant hyperthermia, or other anesthesia-related concerns.
7.The Investigator may choose to exclude patients who have had complications resulting from prior lumbar punctures.
8.The patient has a CNS shunt.
9.The patient has skeletomuscular/spinal abnormalities or other contraindications for the surgical implantation of the IDDD.
10.The patient has a history of poorly controlled seizure disorder.
11.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.
12.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 implantation if applicable), or has ingested such medications within 1 week before any procedures in which any change in clotting activity would be deleterious.
13.The patient has received treatment with any investigational drug or a device 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).
14.The patient has received a hematopoietic stem cell or bone marrow transplant.
15.The patient’s parent(s), or patient’s legal guardian(s) is/are unable to provide consent or the patient cannot provide assent,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified