An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy

• Register: ClinicalTrials.gov
• Last refreshed on: 2 August 2023
• Main ID: NCT01887938
• Date of registration: 20/06/2013
• Prospective Registration: No
• Primary sponsor: Shire
• Public title: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy
• Scientific title: An Open-Label Extension of Study HGT-MLD-070 Evaluating Long Term Safety and Efficacy of Intrathecal Administration of HGT-1110 in Patients With Metachromatic Leukodystrophy
• Date of first enrolment: May 23, 2013
• Target sample size: 24
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01887938
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Argentina, Australia, Brazil, Czech Republic, Czechia, Denmark, France, Germany, Japan

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Participant has participated in Study HGT-MLD-070 (NCT01510028) through Week 40.

2. Participant must have no safety or medical issues that contraindicate participation.

3. The participant, participant's parent(s), or legally authorized representative(s) must
provide written informed consent and/or assent (if applicable) prior to performing any
study-related activities.

Exclusion Criteria:

1. The participant is unable to comply with the protocol (example, is unable to return
for safety evaluations, or is otherwise unlikely to complete the study) as determined
by the investigator.

2. Undergoes bone marrow transplant (BMT), hematopoietic stem cell transplantation
(HSCT), or gene therapy at any point during the study.

3. The participant has any known or suspected hypersensitivity to agents used for
anesthesia or is thought to be at an unacceptably high risk for associated potential
complications of airway compromise or other conditions.

4. The participant is pregnant or breastfeeding.

5. The participant is enrolled in another clinical study that involves clinical
investigations or use of any investigational product (drug or drug delivery device)
other than those used in HGT-MLD-070 (NCT01510028) within 6 months prior to study
enrollment or at any time during the study.

6. The participant has a condition that is contraindicated as described in the
SOPH-A-PORT Mini SIDDD Instructions for Use (IFU), including:

1. The participant has had, or may have, an allergic reaction to the materials of
construction of the SOPH-A-PORT Mini S device.

2. The participant'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 participant has a known or suspected local or general infection.

4. The participant is at risk of abnormal bleeding due to a medical condition or
therapy.

5. The participant has one or more spinal abnormalities that could complicate safe
implantation or fixation.

6. The participant has a functioning CSF shunt device.

7. The participant has shown an intolerance to an implanted device.



Age minimum: 0 Years
Age maximum: 13 Years
Gender: All

Health Condition(s) or Problem(s) studied

Metachromatic Leukodystrophy (MLD)

Intervention(s)

Biological: HGT-1110

Primary Outcome(s)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Time Frame: Baseline to Follow-up (Week 628)]

Presence of Anti-HGT-1110 Antibodies in Cerebrospinal Fluid (CSF) and Serum [Time Frame: Baseline until end of the study (Week 624)]

Secondary Outcome(s)

Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time at Which Serum Concentrations Were Measurable (AUC0-last) of HGT-1110 [Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3]

Area Under the Serum Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of HGT-1110 [Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3]

Clearance (CL/F) of HGT-1110 [Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3]

Concentrations of HGT-1110 in Cerebrospinal Fluid (CSF) [Time Frame: Baseline to End of the study (Week 624)]

Maximum Observed Serum Concentration (Cmax) of HGT-1110 [Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3]

Change From Baseline in Motor Function as Assessed by Gross Motor Function Measure (GMFM-88) Total Score at Week 624 [Time Frame: Baseline, Week 624]

Change From Baseline in the Domain-Specific Caregiver Observed Metachromatic Leukodystrophy Functioning and Outcomes Reporting Tool (COMFORT) Scores [Time Frame: Baseline, Week 624]

Volume of Distribution (Vz/F) of HGT-1110 [Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3]

Terminal Half-Life (t1/2) of HGT-1110 [Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3]

Apparent Terminal Rate Constant (lambda z) of HGT-1110 [Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3]

Change From Baseline in the Adaptive Behavior Composite Standard Score Measured by the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) [Time Frame: Baseline, Week 624]

Time of Maximum Observed Serum Concentration (Tmax) of HGT-1110 [Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3]

Secondary ID(s)

HGT-MLD-071

2012-003775-20

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Takeda Development Center Americas, Inc.