An Extension Study to Determine Safety and Efficacy for Pediatric Patients With MPS Type IIIA Disease Who Participated in Study HGT-SAN-093.

NCT02350816 | Terminated Phase 2 Results DMC

• 2 other identifiers: SHP610-2012014-003960-20
• Study Type: interventional
• Target: 17
• Locations: 7 countries
• Sites: 8

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.

Conditions

Sanfilippo Syndrome; Mucopolysaccharidosis (MPS)

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug

  An AE was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. TEAEs was defined as all AEs from the time of initial IDDD implantation (or first dose if earlier) in either Study NCT02060526 (HGT-SAN-093) or Study NCT02350816 (SHP-610-210) to the data cutoff date (28 Jun 2017), or 30 days after the date of the last dose or 2 weeks after the date of device explant (whichever was later) if early termination occurred. Treatment-emergent AEs were summarized by type (serious, life-threatening), severity (mild, moderate, severe) and degree of relationship to investigational product (Intrathecal Drug Delivery Device (IDDD), device surgical procedure, or intraThecal administration of HGT-1410).

  From start of study drug administration up to follow-up (Week 276)

• Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum

  Number of participants with positive anti-rhHNS antibody status in serum were reported.

  Up to 120 weeks

• Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Cerebro Spinal Fluid (CSF)

  No sufficient pharmacokinetic (PK) samples were collected and analyzed due to early termination of the study.

  Week 0 and 48

• Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Serum

  No sufficient PK samples were collected and analyzed due to early termination of the study.

  Week 0, 48 and 96

• Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF)

  Levels of GAG concentration in CSF was reported. Last measurable data was presented for respective participant up to their last observed time point.

  Up to Week 120

• Levels of Glycosaminoglycan (GAG) Concentration in Urine

  Levels of GAG concentration in Urine were reported. Last measurable data was presented for respective participant up to their last available time point.

  Up to Week 120

Secondary Outcomes (3)

• Change From Baseline Vineland Adaptive Behavior Scales Second Edition (VABS-II)

  Baseline, Week 120

• Change From Baseline in the Developmental Quotient (DQ) Assessed by Neurocognitive Tests

  Baseline, Week 120

• Change From Baseline in Total Cortical Grey Matter Volume

  Baseline, Week 120

Study Arms (4)

HGT-1410 Q2W in Study HGT-SAN-093 randomized to HGT-1410 Q2W

ACTIVE COMPARATOR

Patients in Group 1 will continue HGT-1410 treatment at a dose of 45 mg administered every 2 weeks (Q2W) starting at Week 50, with a cumulative treatment period of up to 42 months (168 weeks) . HGT-1410 will be administered intrathecally (IT) by an indwelling intrathecal drug delivery device (IDDD). HGT-SAN-093 = NCT02060526

Drug: HGT-1410

HGT-1410 Q4W in Study HGT-SAN-093 randomized to HGT-1410 Q4W

ACTIVE COMPARATOR

Patients in Group 2 will continue HGT-1410 treatment at a dose of 45 mg administered every 4 weeks (Q4W) starting at Week 52, with a cumulative treatment period of up to 42 months (168 weeks). HGT-1410 will be administered intrathecally (IT) by an indwelling intrathecal drug delivery device (IDDD).

Drug: HGT-1410

no-treatment in Study HGT-SAN-093 randomized to HGT-1410 Q2W

ACTIVE COMPARATOR

Patients in Group 3A will receive an IDDD following informed consent and will be randomized in a 1:1 allocation ratio to begin HGT-1410 treatment at a dose of 45 mg administered every 2 weeks (Q2W) starting at Week 0 of the extension study, with a cumulative treatment period of up to 30 months (120 weeks). HGT-1410 will be administered intrathecally (IT) by an indwelling intrathecal drug delivery device (IDDD).

Drug: HGT-1410

no-treatment in Study HGT-SAN-093 randomized to HGT-1410 Q4W

ACTIVE COMPARATOR

Patients in Group 3B will receive an IDDD following informed consent and will be randomized in a 1:1 allocation ratio to begin HGT-1410 treatment at a dose of 45 mg administered every 4 weeks (Q4W) starting at Week 0 of the extension study, with a cumulative treatment period of up to 30 months (120 weeks). HGT-1410 will be administered intrathecally (IT) by an indwelling intrathecal drug delivery device (IDDD).

Drug: HGT-1410

Interventions

HGT-1410 DRUG

HGT-1410 administered according to Patient Group assignment.

Also known as: Recombinant Human Heparan N Sulfatase

HGT-1410 Q2W in Study HGT-SAN-093 randomized to HGT-1410 Q2W; HGT-1410 Q4W in Study HGT-SAN-093 randomized to HGT-1410 Q4W; no-treatment in Study HGT-SAN-093 randomized to HGT-1410 Q2W; no-treatment in Study HGT-SAN-093 randomized to HGT-1410 Q4W

Eligibility Criteria

• Age: 12 Months - 48 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients must meet all of the following criteria to be considered eligible for enrollment:
• Patient has completed through at least the Week 48 visit of Study HGT-SAN-093
• 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

You may not qualify if:

• Patients will be excluded from the study if any of the following criteria are met:
• 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\*
• 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
• The patient has a known hypersensitivity to any of the components of HGT-1410
• 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
• 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
• The patient has a condition that is contraindicated as described in the SOPH-A-PORT® Mini S IDDD Instructions for Use, including:
• The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT ® Mini S device
• 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
• The patient's drug therapy requires substances known to be incompatible with the materials of construction
• The patient has a known or suspected local or general infection
• The patient is at risk of abnormal bleeding due to a medical condition or therapy
• The patient has one or more spinal abnormalities that could complicate safe implantation or fixation
• The patient has a functioning CSF shunt device
• The patient has shown an intolerance to an implanted device

Sponsors & Collaborators

• Shire: lead

Study Sites (8)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Chu Bicetre, Le Kremlin-Bicêtre

Paris, 94270, France

Location

Universitätsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Azienda Socio Sanitaria Territoriale - Asst di Monza

Monza, 20900, Italy

Location

Academisch Medisch Centrum Amsterdam

Amsterdam, 22660, Netherlands

Location

Hospital Universitario Vall D'hebron - Ppds

Barcelona, 08035, Spain

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Mucopolysaccharidosis III; Mucopolysaccharidoses

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

The study was terminated as prespecified efficacy criteria were not met and study did not yield clinical proof-of-concept, prompting a decision to discontinue further clinical development of HGT-1410. Hence efficacy parameters were not evaluated.

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2015
• First Posted: January 30, 2015
• Study Start: April 8, 2015
• Primary Completion: April 12, 2019
• Study Completion: April 12, 2019
• Last Updated: June 11, 2021
• Results First Posted: April 20, 2020

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

IT (1); NL (1); GB (1); ES (1); US (2); DE (1); FR (1)