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

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2010-021348-16-GB
• Date of registration: 20/12/2010
• Prospective Registration: Yes
• Primary sponsor: Shire Human Genetic Therapies, Inc
• Public title: Extension of Study HGT-SAN-055 Evaluating Administration of rhHNS in Patients With Sanfilippo Syndrome Type A (MPS IIIA)
• Scientific 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)
• Date of first enrolment: 09/02/2011
• Target sample size: 7
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021348-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands, United Kingdom

Contacts

• Name: Alkisti Rouvas
• Affiliation: Shire Human Genetic Therapies Inc

• Name: Alkisti Rouvas
• Affiliation: Shire Human Genetic Therapies Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet all of the following criteria to be considered eligible for enrollment:
1. The patients must have completed Study HGT-SAN-055 and, in 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 has voluntarily signed an Institutional Review Board / Independent Ethics Committee-approved informed consent (and assent, if applicable) form after all relevant aspects of the study have been explained and discussed with the patient, patient’s parent(s), 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 study 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
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:
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-055 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 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Sanfilippo Syndrome Type A or Mucopolysaccharidosis (MPS IIIA)
MedDRA version: 19.1 Level: LLT Classification code 10056918 Term: Sanfilippo's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 19.1 Level: PT Classification code 10056890 Term: Mucopolysaccharidosis III System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Recombinant human heparan N-sulfatase (rhHNS)
Product Code: HGT-1410
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not available
Current Sponsor code: HGT-1410
Other descriptive name: Recombinant human heparan N-sulfatase
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

Main Objective: 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.

Secondary Objective: To collect as measures of drug efficacy, over an extended treatment period (as change from baseline), the following: clinical, neurological, cognitive, behavioral, functional, and quality of life (QoL) assessments, together with potential imaging and biochemical biomarkers.

Timepoint(s) of evaluation of this end point: 8.5 years (103 months)

Primary end point(s): To determine the long-term safety of intrathecal rhHNS administration, as 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(s)

Secondary end point(s): -Standardized neurocognitive and behavioral assessments
-Concentration of rhHNS in cerebrospinal fluid (CSF) and serum
-Concentration of inflammatory cytokines in serum and CS-Concentration of safety and potential surrogate efficacy biomarkers in CSF, urine, and serum
-Concentration of heparan sulfate and heparan sulfate derivatives in urine, plasma and serum
-Brain magnetic resonance imaging (MRI) and auditory brainstem response (ABR), aka Brainstem Auditory Evoked Potentials.

Timepoint(s) of evaluation of this end point: 8.5 years (103 months)

Secondary ID(s)

HGT-SAN-067

NCT01299727

Source(s) of Monetary Support

Shire Human Genetic Therapies, Inc

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 21/09/2019
• Date Completed: 27/02/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-021348-16/results