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Open-Label Extension Study of Recombinant Human Arylsulfatase A (HGT-1111) in Late Infantile MLD

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ClinicalTrials.gov Identifier: NCT00681811
Recruitment Status : Terminated (Terminated prior to planned completion date due to lack of efficacy.)
First Posted : May 21, 2008
Results First Posted : November 8, 2013
Last Update Posted : August 5, 2015
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Late Infantile Metachromatic Leukodystrophy
Intervention Drug: HGT-1111
Enrollment 11
Recruitment Details Children with an established diagnosis of late metachromatic leukodystrophy (MLD) due to arylsulfatase A (ASA) deficiency were recruited.
Pre-assignment Details All participants who completed Study HGT-MLD-048 (NCT00633139) participated in this study.
Arm/Group Title 100 U/kg HGT-1111 200 U/kg HGT-1111
Hide Arm/Group Description Participants received 100 units per kilogram (U/kg) of HGT1111 intravenous (IV) infusion every other week. Participants received 200 U/kg of HGT1111 IV infusion every other week.
Period Title: Overall Study
Started 6 5
Completed 3 1
Not Completed 3 4
Reason Not Completed
Adverse Event             1             1
Withdrawal by Subject             2             2
Non-compliance             0             1
Arm/Group Title 100 U/kg HGT1111 200 U/kg Total
Hide Arm/Group Description Participants received 100 U/kg of HGT1111 IV infusion every other week. Participants received 200 U/kg of HGT1111 IV infusion every other week. Total of all reporting groups
Overall Number of Baseline Participants 6 5 11
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 5 participants 11 participants
<=18 years
6
 100.0%
5
 100.0%
11
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 6 participants 5 participants 11 participants
53.14  (10.526) 49.99  (8.752) 51.71  (9.420)
[1]
Measure Description: Age at Week 54 or Week 56 in HGT-MLD-049 (NCT00681811)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 5 participants 11 participants
Female
3
  50.0%
3
  60.0%
6
  54.5%
Male
3
  50.0%
2
  40.0%
5
  45.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Denmark Number Analyzed 6 participants 5 participants 11 participants
6 5 11
1.Primary Outcome
Title Days of Exposure to HGT-1111
Hide Description End of study was defined as until HGT-1111 was commercially available, the participant’s participation was discontinued, or the study was terminated by the Sponsor.
Time Frame Baseline until end of study (Week 139)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all enrolled participants who received at least one study infusion (or any portion of a dose) of HGT-1111.
Arm/Group Title 100 U/kg HGT-1111 200 U/kg HGT-1111
Hide Arm/Group Description:
Participants received 100 U/kg of HGT1111 IV infusion every other week.
Participants received 200 U/kg of HGT1111 IV infusion every other week.
Overall Number of Participants Analyzed 6 5
Mean (Standard Deviation)
Unit of Measure: Days
644.7  (276.11) 544.8  (397.27)
2.Secondary Outcome
Title Level of Cerebrospinal Fluid (CSF) Sulfatide
Hide Description Level of CSF sulfatide measured at 6-month intervals in HGT-MLD-049 (NCT00681811).
Time Frame Baseline until end of study (Week 139)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population. "Number of participants analysed" signifies participants who were evaluable for the respective arms under this outcome measure.
Arm/Group Title 100 U/kg HGT-1111 (Month 6) 200 U/kg HGT-1111 (Month 6) 100 U/kg HGT-1111 (Month 12) 200 U/kg HGT-1111 (Month 12) 100 U/kg HGT-1111 (Month 18) 200 U/kg HGT-1111 (Month 18) 100 U/kg HGT-1111 (Month 24) 200 U/kg HGT-1111 (Month 24)
Hide Arm/Group Description:
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 6.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 6.
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 12.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 12.
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 18.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 18.
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 24.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 24.
Overall Number of Participants Analyzed 5 4 5 3 3 3 1 2
Mean (Standard Deviation)
Unit of Measure: nanomole per liter (nmol/L)
685.0  (522.79) 732.5  (545.06) 745.0  (525.12) 1150.0  (676.39) 700.0  (526.78) 850.0  (491.81) 900.0 [1]   (NA) 837.5  (441.94)
[1]
Standard deviation could not be reported as there was only 1 evaluable participant.
3.Secondary Outcome
Title Level of White Matter Metabolites
Hide Description Level of white matter metabolites [N-acetyl Aspartate (NAA)] measured at 6-month intervals in HGT-MLD-049 (NCT00681811).
Time Frame Baseline until end of study (Week 139)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population. "Number of participants analysed" signifies participants who were evaluable for the respective arms under this outcome measure. No participants were analysed after Month 18, hence, data were not available after Month 18.
Arm/Group Title 100 U/kg HGT-1111 (Month 6) 200 U/Kg-HGT-1111(Month 6) 100 U/kg- HGT-1111 (Month 12) 200 U/kg HGT-1111 (Month 12) 100 U/kg- HGT-1111(Month 18) 200 U/kg HGT-1111 (Month 18)
Hide Arm/Group Description:
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 6.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 6.
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 12.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 12.
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 18.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 18.
Overall Number of Participants Analyzed 4 4 5 2 2 2
Mean (Standard Deviation)
Unit of Measure: nmol/L
0.528  (0.176) 0.385  (0.237) 0.598  (0.208) 0.470  (0.198) 0.510  (0.141) 0.805  (0.445)
4.Secondary Outcome
Title Score of Gross Motor Function Measurement (GMFM)
Hide Description Gross motor function was measured using GMFM-88 at 6-month intervals. The GMFM-88 item scores were 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) to 264 (maximum). Decrease in GMFM score indicates disease progression.
Time Frame Baseline until end of study (Week 139)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population. "Number of participants analysed" signifies participants who were evaluable for the respective arms under this outcome measure.
Arm/Group Title 100 U/kg HGT-1111 (Month 6) 200 U/kg HGT-1111 (Month 6) 100 U/kg HGT-1111 (Month 12) 200 U/kg HGT-1111 (Month 12) 100 U/kg HGT-1111 (Month 18) 200 U/kg HGT-1111 (Month 18) 100 U/kg HGT-1111 (Month 24) 200 U/kg HGT-1111 (Month 24)
Hide Arm/Group Description:
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 6.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 6.
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 12.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 12.
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 18.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 18.
Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 24.
Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 24.
Overall Number of Participants Analyzed 5 5 5 3 4 2 2 2
Mean (Standard Deviation)
Unit of Measure: scores on a scale
16.8  (11.30) 9.2  (11.71) 15.6  (15.84) 8.7  (9.29) 16.8  (13.60) 9.0  (5.66) 14.5  (10.61) 13.0  (11.31)
Time Frame Up to end of study (Week 139) which was defined as until HGT-1111 was commercially available, the patient's participation was discontinued, or the study was terminated by the Sponsor.
Adverse Event Reporting Description All other adverse events (>5% reporting frequency) reported here are related to drug administration, all were infusion-related reactions.
 
Arm/Group Title 100 U/kg HGT1111 200 U/kg HGT1111
Hide Arm/Group Description Participants received 100 U/kg of HGT1111 IV infusion every other week. Participants received 200 U/kg of HGT1111 IV infusion every other week.
All-Cause Mortality
100 U/kg HGT1111 200 U/kg HGT1111
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
100 U/kg HGT1111 200 U/kg HGT1111
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/6 (33.33%)      4/5 (80.00%)    
Gastrointestinal disorders     
Gastrooesophageal reflux disease  1  1/6 (16.67%)  1 1/5 (20.00%)  1
Diarrhoea  1  1/6 (16.67%)  1 0/5 (0.00%)  0
General disorders     
Pyrexia  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Infections and infestations     
Lower respiratory track infection  1  1/6 (16.67%)  3 0/5 (0.00%)  0
Catheter bacteraemia  1  1/6 (16.67%)  2 0/5 (0.00%)  0
Bronchitis acute  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Pneumonia  1  0/6 (0.00%)  0 2/5 (40.00%)  3
Pseudomonas infection  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Metabolism and nutrition disorders     
Malnutrition  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Dehydration  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Nervous system disorders     
Convulsion  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Epilepsy  1  0/6 (0.00%)  0 2/5 (40.00%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
100 U/kg HGT1111 200 U/kg HGT1111
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      5/5 (100.00%)    
Ear and labyrinth disorders     
Ear pain  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Eye disorders     
Conjunctival oedema  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Visual acuity reduced  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Eyelid oedema  1  2/6 (33.33%)  2 0/5 (0.00%)  0
Gastrointestinal disorders     
Constipation  1  1/6 (16.67%)  1 2/5 (40.00%)  2
Diarrhoea  1  1/6 (16.67%)  2 0/5 (0.00%)  0
Gastritis  1  2/6 (33.33%)  2 1/5 (20.00%)  1
Gastrooesophageal reflux disease  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Toothache  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Vomiting  1  3/6 (50.00%)  15 3/5 (60.00%)  10
Reflux gastritis  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Nausea  1  3/6 (50.00%)  9 3/5 (60.00%)  3
Regurgitation of food  1  1/6 (16.67%)  1 0/5 (0.00%)  0
General disorders     
Disease progression  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Adverse drug reaction  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Generalised oedema  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Pyrexia  1  4/6 (66.67%)  16 4/5 (80.00%)  4
Infections and infestations     
Gastroenteritis  1  1/6 (16.67%)  1 1/5 (20.00%)  2
Herpes simplex  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Ear infection  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Bronchitis acute  1  1/6 (16.67%)  1 2/5 (40.00%)  2
Bronchitis  1  3/6 (50.00%)  4 3/5 (60.00%)  4
Infection  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Eye infection  1  1/6 (16.67%)  1 2/5 (40.00%)  3
Influenza  1  1/6 (16.67%)  2 1/5 (20.00%)  2
Laryngitis  1  1/6 (16.67%)  1 1/5 (20.00%)  1
Lung infection  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Nasopharyngitis  1  4/6 (66.67%)  12 1/5 (20.00%)  2
Oral candidiasis  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Rhinitis  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Pharyngitis  1  2/6 (33.33%)  5 2/5 (40.00%)  4
Pneumonia  1  1/6 (16.67%)  1 1/5 (20.00%)  1
Viral pharyngitis  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Varicella  1  1/6 (16.67%)  1 1/5 (20.00%)  1
Scarlet fever  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Sinusitis  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Urinary tract infection  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Tooth infection  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Injury, poisoning and procedural complications     
Joint dislocation  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Feeding tube complication  1  1/6 (16.67%)  1 1/5 (20.00%)  2
Investigations     
Blood alkaline phosphatase increased  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Blood iron increased  1  1/6 (16.67%)  1 1/5 (20.00%)  1
Heart rate increased  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Platelet count increased  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Weight decreased  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Metabolism and nutrition disorders     
Malnutrition  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Nervous system disorders     
Dystonia  1  1/6 (16.67%)  1 1/5 (20.00%)  2
Depressed level of consciousness  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Convulsion  1  0/6 (0.00%)  0 1/5 (20.00%)  3
Epilepsy  1  1/6 (16.67%)  1 2/5 (40.00%)  3
Febrile convulsion  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Hypotonia  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Muscle spasticity  1  2/6 (33.33%)  5 2/5 (40.00%)  3
Syncope  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Psychiatric disorders     
Sleep disorder  1  0/6 (0.00%)  0 2/5 (40.00%)  2
Mental status changes  1  1/6 (16.67%)  1 1/5 (20.00%)  1
Reproductive system and breast disorders     
Phimosis  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Respiratory, thoracic and mediastinal disorders     
Increased bronchial secretion  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Epistaxis  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Cough  1  3/6 (50.00%)  5 0/5 (0.00%)  0
Bronchospasm  1  0/6 (0.00%)  0 2/5 (40.00%)  2
Asthma  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Pharyngolaryngeal pain  1  1/6 (16.67%)  1 2/5 (40.00%)  2
Respiratory distress  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Skin and subcutaneous tissue disorders     
Urticaria generalised  1  0/6 (0.00%)  0 2/5 (40.00%)  4
Swelling face  1  1/6 (16.67%)  4 1/5 (20.00%)  1
Rash  1  2/6 (33.33%)  9 3/5 (60.00%)  6
Urticaria  1  1/6 (16.67%)  13 2/5 (40.00%)  11
Vascular disorders     
Pallor  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Flushing  1  1/6 (16.67%)  1 3/5 (60.00%)  8
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Norman Barton
Organization: Shire Human Genetic Therapies, Inc.
Phone: 781-482-9297
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00681811     History of Changes
Other Study ID Numbers: HGT-MLD-049
2008-000084-41 ( EudraCT Number )
First Submitted: May 19, 2008
First Posted: May 21, 2008
Results First Submitted: September 26, 2012
Results First Posted: November 8, 2013
Last Update Posted: August 5, 2015