Metazym for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Cohort 1	Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Cohort 2	Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Cohort 3	Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.

Participant Flow:   Overall Study

	Cohort 1	Cohort 2	Cohort 3
STARTED	4	5	4
COMPLETED	4	4	4
NOT COMPLETED	0	1	0
Participant's (guardian's) decision	0	1	0

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population included all participants who received at least 1 dose of study drug.

Reporting Groups

	Description
Cohort 1	Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Cohort 2	Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Cohort 3	Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Total	Total of all reporting groups

Baseline Measures

	Cohort 1	Cohort 2	Cohort 3	Total
Overall Participants Analyzed  [Units: Participants]	4	5	4	13
Age  [Units: Months] Mean (Standard Deviation)	36.25  (9.32)	41.80  (10.13)	30.75  (7.27)	36.69  (9.59)
Gender  [Units: Participants]
Female	2	3	3	8
Male	2	2	1	5

1.  Primary:

Number of Participants With Treatment-emergent Adverse Events (TEAEs)   [ Time Frame: From study drug administration up to Week 28 ]

2.  Primary:

Change From Baseline in Gross Motor Function Measure (GMFM) at Week 26   [ Time Frame: Baseline, Week 26 ]

3.  Primary:

Change From Baseline in Cerebrospinal Fluid (CSF) Sulfatide at Week 26   [ Time Frame: Baseline, Week 26 ]

4.  Primary:

Number of Participants With Shift From Baseline to Week 26 in Sulfatide Levels in Urine   [ Time Frame: Baseline up to Week 26 ]

5.  Primary:

Change From Baseline in Mullen’s Scales of Early Learning at Week 26   [ Time Frame: Baseline, Week 26 ]

6.  Primary:

Maximum Plasma Drug Concentration (Cmax) of Recombinant Human Arylsulphatase A (rhASA)   [ Time Frame: Pre-dose and post-dose at 20, 40, 90 minutes, 3, 6 and 8 hours on Day 0, 40 minutes post-dose at Week 4, Pre-dose and post-dose at 20, 40, 90 minutes, 3, 6 and 8 hours at Week 8 ]

7.  Primary:

Arylsulfatase A (ASA) Activity in Leukocytes   [ Time Frame: Pre-dose and post-dose at 24 hours on Day 0 and at Weeks 8 and 26 ]

8.  Secondary:

Change From Baseline in Nerve Conduction Velocity at Week 26   [ Time Frame: Baseline, Week 26 ]

9.  Secondary:

Number of Participants Who Had Undergone Nerve Biopsy and Had a Normal Nerve at Both Baseline and Week 26   [ Time Frame: Baseline, Week 26 ]

10.  Secondary:

Number of Participants With Shift From Baseline to Week 26 in Magnetic Resonance Imaging (MRI)-Loes Scores   [ Time Frame: Baseline up to Week 26 ]

11.  Secondary:

Change From Baseline in Paediatric Evaluation of Disability Inventory (PEDI) Scores at Week 26   [ Time Frame: Baseline, Week 26 ]

12.  Other Pre-specified:

Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Biochemistry   [ Time Frame: Baseline up to Week 26 ]

13.  Other Pre-specified:

Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Coagulation   [ Time Frame: Baseline up to Week 26 ]

14.  Other Pre-specified:

Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Genotyping   [ Time Frame: Baseline up to Week 26 ]

15.  Other Pre-specified:

Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Hematology   [ Time Frame: Baseline up to Week 26 ]

16.  Other Pre-specified:

Number of Participants With Abnormal Findings in Urine Analysis   [ Time Frame: Baseline up to Week 26 ]

17.  Other Pre-specified:

Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings   [ Time Frame: Baseline up to Week 26 ]

18.  Other Pre-specified:

Change From Baseline in Chitotriosidase at Week 26   [ Time Frame: Baseline, Week 26 ]

19.  Other Pre-specified:

Change From Baseline in Neurofilament Proteins (NFP), Glial Fibrillary Acidic Protein (GFAP) and Tauprotein in Cerebrospinal Fluid (CSF) at Week 26   [ Time Frame: Baseline, Week 26 ]

20.  Other Pre-specified:

Change From Baseline in Amplitude at Week 26   [ Time Frame: Baseline, Week 26 ]

21.  Other Pre-specified:

Physical Examination Results   [ Time Frame: Baseline up to Week 26 ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
ASA activity in leukocytes could not be included in basic results format as the results were presented graphically. Due to quick disappearance of rhASA from plasma, rhASA levels were not possible to report.