Clinical trial NCT02350816: An Extension Study to Determine Safety and Efficacy for Pediatric Patients With MPS Type IIIA Disease Who Participated in Study HGT-SAN-093.
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sanfilippo Syndrome
Mucopolysaccharidosis (MPS)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-01-30
Enrollment: 17
Sex: ALL
Minimum age (years): 12
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This extension study will allow participants to continue receiving treatment with HGT-1410 and to initiate treatment in patients who received no-treatment in Study HGT-SAN-093, and will evaluate the long-term safety and efficacy of the study drug.


Eligibility 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

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
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-A-PORT® Mini S IDDD Instructions for Use, including:

   1. The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT ® Mini S device
   2. 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
   3. The patient's drug therapy requires substances known to be incompatible with the materials of construction
   4. The patient has a known or suspected local or general infection
   5. The patient is at risk of abnormal bleeding due to a medical condition or therapy
   6. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation
   7. The patient has a functioning CSF shunt device
   8. 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug
timeFrame: From start of study drug administration up to follow-up (Week 276)
measure: Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum
timeFrame: Up to 120 weeks
measure: Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Cerebro Spinal Fluid (CSF)
timeFrame: Week 0 and 48
measure: Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Serum
timeFrame: Week 0, 48 and 96
measure: Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF)
timeFrame: Up to Week 120
measure: Levels of Glycosaminoglycan (GAG) Concentration in Urine
timeFrame: Up to Week 120
Secondary outcomes:
measure: Change From Baseline Vineland Adaptive Behavior Scales Second Edition (VABS-II)
timeFrame: Baseline, Week 120
measure: Change From Baseline in the Developmental Quotient (DQ) Assessed by Neurocognitive Tests
timeFrame: Baseline, Week 120
measure: Change From Baseline in Total Cortical Grey Matter Volume
timeFrame: Baseline, Week 120
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Paris
country: France
facility: Chu Bicetre, Le Kremlin-Bicêtre
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale - Asst di Monza
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum Amsterdam
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D'hebron - Ppds
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: