Primary Objective(s): To evaluate long-term safety in patients with mucopolysaccharidosis type IIIA disease (MPS IIIA or Sanfilippo Type A) who received HGT-1410Secondary Objective(s):To evaluate:• The long-term cognitive function as measured by the…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Study Endpoints:
Safety evaluations include the assessment of adverse events (AEs), IDDD related
issues, laboratory values, anti-rhHNS antibody development, vital signs,
physical examination findings, and ECG results
Secondary outcome
The secondary endpoints of this study are:
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
The SOPH-A-PORT ® Mini S device will be evaluated using assessments of device
implantation, device function, device longevity, and AEs associated with the
implant surgery or device.
The PK endpoint is to determine the pharmacokinetic behavior of HGT-1410 in
serum. The pharmacokinetic behavior of HGT-1410 in CSF will also be determined
in patients who received no-treatment in Study HGT-SAN-093.
The pharmacodynamic (PD) endpoint is to determine the GAG concentrations in CSF
and urine.
The health status endpoint is the ITQoL scores at each assessment time and the
corresponding change from Baseline.
The health economic and outcome research endpoints evaluate key HCUQ variables,
such as the number of emergency room visits, caregiver employment status
(full-time [FT], part-time [PT], or not working [NW]), and the number of hours
of additional paid help needed by caregivers, over the course of the study.
Background summary
MPS IIIA is a rare, inherited genetic disorder in which an enzyme called
heparan N-sulfatase (HNS) or sulfamidase is missing or not working properly.
This enzyme is important in the breakdown of mucopolysaccharides (MPSs) or
glycosaminoglycan (s) (or GAGs), which are large complex sugars used in the
building of tissues of the body. When sulfamidase is missing, or not working
properly, it causes GAGs to build up in the body, in the small parts of the
cells, called lysosomes. As time goes on, cells in the body become clogged with
the sugar and are injured. As a result, patients with MPS IIIA develop problems
affecting the body, especially the central nervous system (CNS: the brain and
spinal cord). These patients typically do not develop normal abilities
regarding language, learning, and many of the normal tasks that are part of
growing up or the patients may develop these abilities and then lose them as
time goes on and the GAGs build up within their body. The study Sponsor, Shire
HGT, is
developing the study drug, recombinant human heparan N-sulfatase (rhHNS;
HGT-1410) as an enzyme replacement therapy (ERT) for patients with MPS IIIA.
Study objective
Primary Objective(s):
To evaluate long-term safety in patients with mucopolysaccharidosis type IIIA
disease (MPS IIIA or Sanfilippo Type A) who received HGT-1410
Secondary Objective(s):
To evaluate:
• 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
Exploratory Objective
To evaluate the safety and performance of the SOPH-A-PORT ® Mini S device
Pharmacokinetic and Pharmacodynamic Objectives
To evaluate:
• The pharmacokinetics (PK) of HGT-1410 in serum
• The PK of HGT-1410 in cerebrospinal fluid (CSF), in patients who received no
treatment in Study HGT-SAN-093
• The concentration of glycosaminoglycans (GAG) in CSF and urine in patients
who received HGT-1410
Health Status Objective
To evaluate health status as measured by the Infant Toddler Quality of Life
Questionnaire* (ITQoL) instrument in patients who received HGT-1410
Health Economics and Outcomes Research Objectives
To evaluate healthcare resource utilization, as evaluated by the Healthcare
Utilization Questionnaire (HCUQ), in patients who received HGT-1410.
Study design
This is an open label study for patients who completed through at least the
Week 48 Visit of Study HGT SAN 093. Patients who originally received HGT-1410
in Study HGT SAN-093 will remain on the same dosing regimen as they received in
Study HGT SAN-093; Group 1 will receive HGT-1410 Q2W and Group 2 will received
HGT 1410 Q4W. Patients in Groups 1 and 2 will begin treatment at Week 50 and
Week 52, respectively, of this extension study (Study SHP-610-201). Patients
who originally received no treatment in Study HGT-SAN-093 (Group 3) will
receive an IDDD following informed consent and will be re-randomized in a 1:1
allocation ratio to receive HGT-1410 via a Q2W or Q4W dosing regimen (Groups 3A
and 3B, respectively) in Study SHP-610-201. Patients in Groups 3A and 3B will
begin treatment on Week 0 of the extension study.
Intervention
Investigational Product, Dose, and Mode of Administration:
HGT-1410 at a dose of 45 mg administered every 2 weeks (Q2W) or 45 mg
administered every 4 weeks (Q4W). HGT 1410 will be administered intrathecally
(IT) by an indwelling intrathecal drug delivery device (IDDD).
Device, Intended Use
The SOPH-A-PORT ® Mini S is a system intended for implantation by physicians.
The SOPH-A-PORT ® Mini S, once implanted, allows healthcare personnel to
administer HGT-1410 indicated for intrathecal delivery intermittently over a
long period of time.
Study burden and risks
Please refer to the overview of procedures in the protocol (appendix 1-4) for a
complete overview.
The following procedures will be performed in the context of the research and
are different/additional in comparison with the standard treatment.
- Complete Questionnaires (5x 5 times in treatment arm 1 and 2; 6 times in
treatment arm 3)
- MRI (2x voor behandelgroep 1 en 2; 4x voor behandelgroep 3);
- Administration IP(all treatment groups
- Lumbar punction (treatment group 3)
- Liquor sampling 22 times (for all treatment groups) The patients in group
3A/B will have 2 extra sampling in week 0 and 48.
- Implantation of IDDD (treatment group 3)
- X-rays (2x in treatment group 3).
Pain and headache during or after the injection of study drug are possible. The
injection procedure may be performed incorrectly, including injecting the wrong
medicine through the port, injecting study drug outside the port into the
surrounding tissue, or using the wrong type of needle or improper technique
while injecting medicine into the port. Injection of HGT-1410, as with any
protein, carries with it the risk of an infusion-related reaction. Tingling or
painful sensation to the lower legs.
Shire Way 300
Lexington MA, 02421
US
Shire Way 300
Lexington MA, 02421
US
Listed location countries
Age
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.
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003960-20-NL |
| CCMO | NL52203.018.15 |