An extension to the safety, tolerability and preliminary efficacy study of Idursulfase-IT in patients with Hunter syndrome associated with learning disability

• Register: EUCTR
• Last refreshed on: 30 November 2020
• Main ID: EUCTR2011-000212-25-GB
• Date of registration: 24/02/2011
• Prospective Registration: Yes
• Primary sponsor: Shire HGT Inc
• Public title: An extension to the safety, tolerability and preliminary efficacy study of Idursulfase-IT in patients with Hunter syndrome associated with learning disability
• Scientific title: An Open-Label Extension of Study HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Intrathecal Idursulfase-IT Administered in Conjunction with Intravenous Elaprase® in Pediatric Patients with Hunter Syndrome and Cognitive Impairment
• Date of first enrolment: 05/01/2012
• Target sample size: 15
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000212-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, United Kingdom, United States

Contacts

• Name: Alkisti Rouvas
• Affiliation: Shire HGT

• Name: Alkisti Rouvas
• Affiliation: Shire HGT

Key inclusion & exclusion criteria

Inclusion criteria:
1 Patients must have completed all study requirements and EOS asessments for Study HGT-HIT-045 prior to enrolling in Study HGT-HIT-046 and must have no safety or medical issues that contraindicate participation.

2 The patient’s parent(s) or legally authorized representative(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 representative(s) and the patient’s assent, as relevant, must be obtained.

3 The patient has received and tolerated a minimum of 12 months of treatment with weekly IV infusions of Elaprase and has received 80% of the total planned infusions within the last 6 months.

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 is enrolled in another clinical study that involves clinical investigations or use
of any investigational product (drug or device) other than the PORT-A-CATH IDDD
within 30 days prior to study enrollment or at any time during the study.
2 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.

3 The patient has experienced an adverse reaction to study drug in Study HGT-HIT-045 that contraindicates further treatment with intrathecal idursulfase-IT.
4 The patient has a known hypersensitivity to any of the components of idursulfase-IT.

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-A-PORT 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

An additional exclusion criterion for patients who were previously untreated with intrathecal idursulfase-IT in Study HGT-HIT-045:
1. The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O.



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Treatment of Hunter syndrome and cognitive impairment
MedDRA version: 20.1 Level: PT Classification code 10056889 Term: Mucopolysaccharidosis II System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Idursulfase(12S)-IT
Product Code: 12S-IT
Pharmaceutical Form: Solution for injection
INN or Proposed INN: idursulfase
CAS Number: 50936-59-9
Current Sponsor code: 12S-IT
Other descriptive name: Idursulfase-IT
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): Safety of intrathecal idursulfase-IT administration. Safety will be measured by AEs (by type and severity), changes in clinical laboratory testing (serum chemistry including liver function tests, hematology, urinalysis), 12-lead ECG, CSF chemistries (contingent on sample availability; cell counts, glucose, and protein), and anti-idursulfase antibodies and antibodies having enzyme neutralizing activity in CSF and serum.

Secondary Objective: - To determine the serum pharmacokinetic (PK) profile of idursulfase when administered as intrathecal idursulfase-IT and in conjunction with Elaprase
- To determine the effect of intrathecal idursulfase-IT, given in conjunction with Elaprase, on CSF biomarkers (eg, glycosaminoglycan [GAG], including heparan sulfate [HS]/dermatan sulfate [DS]
- To determine the effects of intrathecal idursulfase-IT, given in conjunction with Elaprase, on urinary GAGs

Main Objective: To collect long-term safety data in pediatric patients with Hunter syndrome and cognitive impairment who are receiving intrathecal idursulfase-IT and intravenous
(IV) Elaprase® enzyme replacement therapy

Timepoint(s) of evaluation of this end point: Pre-Treatment timepoints at monthly visits as defined in the protocol.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: PK sampling in blood - several timepoints up to 36 hours following IT injection at week 3 and 23 (initial treatment phase) and at months 19, 31 and 43 (extended treatment phase).

Secondary end point(s): - Serum idursulfase concentration-time profiles and serum PK parameters of idursulfase, administered as intrathecal idursulfase-IT and in conjunction with Elaprase

- Change from baseline in CSF biomarkers (eg, GAG [HS/DS]
- Change from baseline in urinary GAGs

Secondary ID(s)

HGT-HIT-046

Source(s) of Monetary Support

Shire HGT

Ethics review

Status: Approved
Approval date: 05/01/2012
Contact: