Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
An AE is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational drug product-related. TEAEs are defined as all AEs occurring or worsening at or after the first dose of investigational drug product in HGT-MLD-071 or ongoing from HGT-MLD-070 at the time of enrollment into HGT-MLD-071. |
Baseline to Follow-up (Week 628) |
|
Primary |
Presence of Anti-HGT-1110 Antibodies in Cerebrospinal Fluid (CSF) and Serum |
The presence of anti-HGT-1110 antibodies in CSF and serum will be assessed. |
Baseline until end of the study (Week 624) |
|
Secondary |
Change From Baseline in Motor Function as Assessed by Gross Motor Function Measure (GMFM-88) Total Score at Week 624 |
The GMFM-88 item scores can be used to calculate a domain-specific percent score for each of the 5 GMFM-88 dimensions, which are the following: Lying and rolling; Sitting; Crawling and kneeling; Standing; Walking, running, and jumping. Each of the 88 items is rated on a 4-point scale: 0=does not initiate; 1=initiates; 2=partially completes; and 3=completes. The GMFM-88 total scores range from 0% (no mobility) to a score of 100%, that is (i.e,) the score that can be obtained by an average 5-year-old or older child with normal motor abilities. The domain-specific percent scores are averaged to obtain the total score (percent). |
Baseline, Week 624 |
|
Secondary |
Change From Baseline in the Adaptive Behavior Composite Standard Score Measured by the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) |
The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The ABC score ranges from 20 to 160 on which higher scores indicate a higher level of adaptive functioning. A positive change value indicates improvement in adaptive functioning. |
Baseline, Week 624 |
|
Secondary |
Change From Baseline in the Domain-Specific Caregiver Observed Metachromatic Leukodystrophy Functioning and Outcomes Reporting Tool (COMFORT) Scores |
The COMFORT is a questionnaire that will be used to assess health status and the impact of disease on the ability of participants with MLD to carry out activities of daily life. The questionnaire is organized by 8 domains (that is, Personal Care, Positioning, Transfer or Mobility, Eating, Pain and Discomfort During the Day, Sleep, Emotions, Communication, Play and Leisure Activities) and will be completed by the participant's parent(s) or legal representative(s). It will be conducted in available validated languages. The COMFORT scores range from 0 to 100, with higher scores indicating a decline in the functioning. |
Baseline, Week 624 |
|
Secondary |
Maximum Observed Serum Concentration (Cmax) of HGT-1110 |
The Cmax of HGT-1110 will be assessed. |
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 |
Time of Maximum Observed Serum Concentration (Tmax) of HGT-1110 |
The Tmax of HGT-1110 will be assessed. |
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 |
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 |
The AUC0-last of HGT-1110 will be assessed. |
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 |
Area Under the Serum Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of HGT-1110 |
The AUC0-inf of HGT-1110 will be assessed. |
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 |
Apparent Terminal Rate Constant (lambda z) of HGT-1110 |
The lambda z of HGT-1110 will be assessed. |
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 |
Terminal Half-Life (t1/2) of HGT-1110 |
The t1/2 of HGT-1110 will be assessed. |
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 |
Clearance (CL/F) of HGT-1110 |
The CL/F of HGT-1110 will be assessed. |
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 |
Volume of Distribution (Vz/F) of HGT-1110 |
The Vz/F of HGT-1110 will be assessed. |
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 |
Concentrations of HGT-1110 in Cerebrospinal Fluid (CSF) |
Concentrations of HGT-1110 in CSF will be assessed. |
Baseline to End of the study (Week 624) |
|