Recombinant human Arylsulfatase A

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.

The presence of anti-HGT-1110 antibodies in CSF and serum will be assessed.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. Drug-related and device-related types of TEAEs were analyzed and reported. The severity of AEs was assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 grading scale. Severity of all AEs or SAEs was recorded as grade 1, 2, 3, 4, or 5 corresponding, respectively, to a severity of mild, moderate, severe, life-threatening, or fatal. Here SDI refers to surgical device implantation.

Clinical laboratory test included serum chemistry, hematology and urinalysis. Clinical laboratory abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.

Vital sign assessments included blood pressure, heart rate, respiratory rate and body temperature. Vital sign abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. Vital sign abnormalities included pyrexia which was considered as TEAE and was reported.

12-lead ECG was recorded and measured with the participant in rested supine position for at least 10 minutes. ECG abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.

Complete physical examination included evaluation of the port and catheter track. Height or length and weight were recorded and used to calculate growth. Body weight and height measurements were used to calculate the body mass index (BMI). Head circumference was measured in uniform manner for all participants. Clinical significance was defined as any variation in physical findings that had medical relevance resulting in an alteration in medical care. Clinically significant abnormalities related to physical examination were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.

CSF chemistry assessments (including cell counts, glucose and protein) was measured. CSF chemistry abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.

Number of participants with positive anti-SHP611 antibody results in serum and in CSF were reported. A participant was considered positive if they had at least 1 positive result during the study.

Change (percent change) in GMFM is measured from baseline to end of study (Week 52). GMFM is measured using GMFM-88. The GMFM-88 item scores can be summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score is between 0 (minimal) to 3 (maximum). The total GMFM-88 score is between 0 (minimal) to 264 (maximum). Relative changes in GMFM are calculated as percentage change from baseline divided by the age difference in months between first and last visit. The GMFM score decreases over time, which, indicates that the disease worsened over time. Score over time (SOT), data mentioned over mean represents the adjusted mean.

Changes in Mullen's Scales of Early Learning are measured from baseline to end of study (Week 52) using Mullen's Scales of Early Learning. T scores, percentile ranks, and age equivalents can be computed for the four scales separately (visual reception, fine motor, expressive language, and receptive language). Relative change is calculated as percentage change from baseline divided by the age-difference in months between first and last visit. When Mullen's score decreases over time, it indicates the disease worsened over time. Data mentioned over mean represents the adjusted mean.

GMFM was measured using GMFM-88 item scores and summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score was between 0 (minimal) to 3 (maximum). The total GMFM-88 score was between 0 (minimal) and 264 (maximum). The decrease in GMFM score over time indicates worsening of disease over time. Relative change from baseline at Week 26 was calculated as percentage change from baseline divided by the age-difference in months between first and last visit. Adjusted mean and 95 percent (%) confidence intervals were reported.

Relative change from baseline at Week 26 was calculated as percentage change from baseline divided by the age-difference in months between first and last visit. Adjusted mean and 95 percent (%) confidence intervals were reported.

Number of participants with shifts between negative (value=0) and positive (value=1) values in urine sulfatide levels from baseline at Week 26 is reported.

Mullen's Scales of Early Learning is used to assess performance and learning ability in young children. The scale consisted of 144 items that had specific scoring criteria for each item. The scores were converted to T-scores with a decrease in score indicating worsening of disease. Relative change from baseline at Week 26 was calculated as percentage change from baseline divided by the age-difference in months between first and last visit. Adjusted mean and 95 percent (%) confidence intervals were reported.