An Extension Study to Evaluate the Safety and Efficacy of HGT-1410 Administration in Pediatric Patients with Sanfilippo Syndrome Type A

• Register: EUCTR
• Last refreshed on: 3 November 2020
• Main ID: EUCTR2014-003960-20-NL
• Date of registration: 05/03/2015
• Prospective Registration: Yes
• Primary sponsor: Shire Human Genetic Therapies, Inc.
• Public title: An Extension Study to Evaluate the Safety and Efficacy of HGT-1410 Administration in Pediatric Patients with Sanfilippo Syndrome Type A
• Scientific title: An Open-Label Extension of Study HGT-SAN-093 Evaluating the Safety and Efficacy Study of HGT-1410 (Recombinant Human Heparan N Sulfatase) Administration via an Intrathecal Drug Delivery Device in Pediatric Patients with Mucopolysaccharidosis Type IIIA Disease
• Date of first enrolment: 18/08/2015
• Target sample size: 17
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003960-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; 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; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Jeannie Salazar
• Affiliation: Shire, Inc.

• Name: Jeannie Salazar
• Affiliation: Shire, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet all of the following criteria to be considered eligible for enrollment:
1. Patient has completed through at least the Week 48 visit of Study HGT-SAN-093.
2. The patient’s parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board- (IRB-)/Independent Ethics Committee- (IEC-) approved informed consent form after all relevant aspects of the study have been explained and discussed. Consent of the patient’s parent(s) or legally authorized guardian(s) and the patient’s assent, as relevant, must be obtained.
Are the trial subjects under 18? yes
Number of subjects for this age range: 17
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients will be excluded from the study if any of the following criteria are met:
1. The patient, if randomized to treatment in Study HGT-SAN-093, has experienced a decline of more than 20 points in the BSID-III cognitive DQ score between Baseline and the Week 48 visit in Study HGT-SAN-093, AND, upon individual evaluation by the Investigator, has been deemed a treatment failure*.
2. The patient has experienced, in the opinion of the Investigator, a safety or medical issue that contraindicates treatment with HGT-1410, including but not limited to clinically relevant intracranial hypertension, severe infusion-related reactions after treatment with HGT-1410, uncontrollable seizure disorder.
3. The patient has a known hypersensitivity to any of the components of
HGT-1410. Patients with documented infusion-related reactions that are
clinically manageable (for example, with pre-medication or slowing
infusion rate) are not necessarily excluded based on the assessment of
the investigator.
4. The patient is enrolled in another clinical study, other than HGT-SAN-093, that involves clinical investigations or use of any investigational product (drug or [intrathecal/spinal] device) within 30 days prior to study enrollment or at any time during the study.
5. The patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions.
6. The patient has a condition that is contraindicated as described in the SOPH-APORT ® Mini S IDDD Instructions for Use, including:
a.- The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT ® Mini S device
b.- The patient’s body size is too small to support the size of the SOPH-A-PORT ® Mini S Access Port, as judged by the Investigator
c.- The patient’s drug therapy requires substances known to be incompatible with the materials of construction
d.- The patient has a known or suspected local or general infection
e.- The patient is at risk of abnormal bleeding due to a medical condition or therapy
f.- The patient has one or more spinal abnormalities that could complicate safe implantation or fixation
g.- The patient has a functioning CSF shunt device
h.- The patient has shown an intolerance to an implanted device
7. The patient is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the Investigator.
*All treated patients in Study HGT-SAN-093 will have their cognitive development assessed at the Week 48 Visit in Study HGT-SAN-093. If a decline from Baseline of 20 points or less in the BSID-III DQ score is observed, then the patient may proceed into
the Study SHP-610-201 without further evaluation. If a decline from Baseline of more than 20 points in DQ score is observed, then an
individual evaluation by the Investigator will occur to determine if the patient is a treatment failure. This individual evaluation will
take into account the DQ scores, VABS-II score, physical status, and any other information available for that patient at that time. If the Investigator deems the patient to
be a treatment failure, then the patient may not enter the Study SHP-610-201.


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

Health Condition(s) or Problem(s) studied

Sanfilippo Syndrome Type A or Mucopolysaccharidosis (MPS IIIA)
MedDRA version: 20.0 Level: LLT Classification code 10056918 Term: Sanfilippo's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.1 Level: PT Classification code 10056890 Term: Mucopolysaccharidosis III System Organ Class: 10010331 - Congenital, familial and genetic disorders

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

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)

Primary end point(s): Safety is the primary objective of the study and will be assessed during the study by the following:
• collection of adverse events (by type, severity, and relationship to treatment [HGT-1410, the IDDD, device surgical procedure, or IT administration process])
• changes in clinical laboratory testing (serum chemistry, hematology, urinalysis)
• physical examination
• vital signs
• 12-lead electrocardiogram (ECG) recordings
• CSF laboratory parameters (including chemistries, cell counts)
• anti-rhHNS antibodies in CSF and serum, including determination of antibodies having enzyme neutralizing activity

Secondary Objective: To evaluate the following: The long-term cognitive function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) or Kaufman Assessment Battery for Children, 2nd Edition (KABC-II), age-equivalent and developmental quotient (DQ) scores in patients with MPS IIIA who received HGT-1410; the long-term adaptive behavioral function, assessed by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) in patients who received HGT-1410; the total cortical grey matter volume, as assessed by volumetric MRI of the
brain, in patients who received HGT-1410.

Main Objective: To evaluate long-term safety in patients with mucopolysaccharidosis type IIIA disease (MPS IIIA or Sanfilippo Type A) who received HGT-1410

Timepoint(s) of evaluation of this end point: 120 weeks

Secondary Outcome(s)

Secondary end point(s): • The change from Baseline in BSID-III or KABC-II age-equivalent, DQ, and developmental delay scores
• The change from Baseline in adaptive behavioral function domains, assessed by VABS II, using raw scores, age-equivalent scores, and DQ scores
• The change from Baseline in total cortical grey matter volume, as assessed by MRI

Timepoint(s) of evaluation of this end point: 120 weeks

Secondary ID(s)

2014-003960-20-ES

SHP-610-201

Source(s) of Monetary Support

Shire human Genetic Therapies, Inc.

Ethics review

Status: Approved
Approval date: 18/08/2015
Contact:

Results

• Results available: Yes
• Date Posted: 21/09/2019
• Date Completed: 06/03/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-003960-20/results