Trial Outcomes & Findings for Long-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD) (NCT NCT00633139)

Last Updated: 2021-06-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Baseline, 52 Weeks

Results posted on

2021-06-14

Participant Flow

Children with an established diagnosis of late metachromatic leukodystrophy (MLD) due to arylsulfatase A (ASA) deficiency were recruited.

All participants that completed study recombinant human arylsulfatase A (rhASA-01) (NCT00418561) except 1 participant who did not complete (at week 18) the rhASA-01 (NCT00418561) participated in HGT-MLD-048/rhASA-03 (NCT00633139).

Participant milestones

Participant milestones
Measure	Cohort 1 Participants received a single dose of rhASA at 25 units per kilogram (U/kg) intravenous (IV) infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52.	Cohort 2 Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52.	Cohort 3 Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52.
Overall Study STARTED	4	5	4
Overall Study COMPLETED	4	4	3
Overall Study NOT COMPLETED	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 Participants received a single dose of rhASA at 25 units per kilogram (U/kg) intravenous (IV) infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52.	Cohort 2 Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52.	Cohort 3 Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52.
Overall Study Non compliance	0	0	1
Overall Study Withdrawal by Subject	0	1	0

Baseline Characteristics

Long-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=4 Participants Participants received a single dose of rhASA at 25 U/kg IV infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52.	Cohort 2 n=5 Participants Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52.	Cohort 3 n=4 Participants Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52.	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=113 Participants	5 Participants n=163 Participants	4 Participants n=160 Participants	13 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants
Age, Continuous	36.25 months STANDARD_DEVIATION 9.32 • n=113 Participants	41.80 months STANDARD_DEVIATION 10.13 • n=163 Participants	30.75 months STANDARD_DEVIATION 7.27 • n=160 Participants	36.69 months STANDARD_DEVIATION 9.59 • n=483 Participants
Sex: Female, Male Female	2 Participants n=113 Participants	3 Participants n=163 Participants	3 Participants n=160 Participants	8 Participants n=483 Participants
Sex: Female, Male Male	2 Participants n=113 Participants	2 Participants n=163 Participants	1 Participants n=160 Participants	5 Participants n=483 Participants
Region of Enrollment Denmark	4 Participants n=113 Participants	5 Participants n=163 Participants	4 Participants n=160 Participants	13 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline, 52 Weeks

Population: Intent to Treat (ITT) population included all the participants in the study.

Outcome measures

Outcome measures
Measure	Cohort 1 n=4 Participants Participants received a single dose of rhASA at 25 U/kg IV infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52.	Cohort 2 n=5 Participants Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52.	Cohort 3 n=4 Participants Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52.
Relative Changes (%) in Gross Motor Function Measurement (GMFM)	-2.98 Relative % change in total GMFM-88 SOT Interval -6.08 to 0.12	-5.42 Relative % change in total GMFM-88 SOT Interval -8.5 to -2.34	-5.28 Relative % change in total GMFM-88 SOT Interval -8.91 to -1.65

PRIMARY outcome

Timeframe: Baseline, 52 Weeks

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=4 Participants Participants received a single dose of rhASA at 25 U/kg IV infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52.	Cohort 2 n=5 Participants Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52.	Cohort 3 n=4 Participants Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52.
Relative Change in Mullen's Scales of Early Learning	-2.82 Relative % change in Mullen's SOT Interval -6.31 to 0.66	-2.97 Relative % change in Mullen's SOT Interval -6.47 to 0.54	-6.98 Relative % change in Mullen's SOT Interval -11.95 to -2.01

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

Population: ITT population

Changes in CSF sulfatide from baseline to end of study (Week 52). Data mentioned over mean represents the adjusted mean.

Outcome measures

Outcome measures
Measure	Cohort 1 n=4 Participants Participants received a single dose of rhASA at 25 U/kg IV infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52.	Cohort 2 n=5 Participants Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52.	Cohort 3 n=4 Participants Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52.
Change in Cerebrospinal Fluid (CSF) Sulfatide	8.60 %change in CSF sulfatide Interval -0.77 to 17.97	-1.53 %change in CSF sulfatide Interval -8.63 to 5.56	-2.77 %change in CSF sulfatide Interval -14.35 to 8.81

Adverse Events

Cohort 1

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Cohort 2

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort 3

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 n=4 participants at risk Cohort 1: Participants received a single dose of rhASA at 25 U/kg IV infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52.	Cohort 2 n=5 participants at risk Cohort 2: Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52.	Cohort 3 n=4 participants at risk Cohort 3: Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52.
Metabolism and nutrition disorders malnutrition	25.0% 1/4 • Number of events 1 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	40.0% 2/5 • Number of events 2 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	50.0% 2/4 • Number of events 3 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.
Infections and infestations bronchitis acute	25.0% 1/4 • Number of events 1 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	0.00% 0/5 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	0.00% 0/4 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.
Infections and infestations pneumonia	25.0% 1/4 • Number of events 1 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	0.00% 0/5 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	75.0% 3/4 • Number of events 3 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.
Gastrointestinal disorders vomiting	0.00% 0/4 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	20.0% 1/5 • Number of events 1 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	0.00% 0/4 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.
Respiratory, thoracic and mediastinal disorders pneumonia aspiration	0.00% 0/4 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	20.0% 1/5 • Number of events 1 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	25.0% 1/4 • Number of events 1 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.
Eye disorders blindness	0.00% 0/4 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	0.00% 0/5 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	25.0% 1/4 • Number of events 1 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.
Injury, poisoning and procedural complications post procedural vomiting	0.00% 0/4 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	0.00% 0/5 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	25.0% 1/4 • Number of events 1 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.
Gastrointestinal disorders peritonitis	0.00% 0/4 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	0.00% 0/5 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.	25.0% 1/4 • Number of events 1 • 52 weeks of treatment All other adverse events (AEs) (\>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place