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NCT00681811

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

Terminated Phase 2 Results posted Last updated 8 June 2021
What this trial tests

Phase 2 trial testing HGT-1111 in Late Infantile Metachromatic Leukodystrophy in 11 participants. Terminated before completion.

Timeline
20 February 2008
Primary endpoint
22 October 2010
22 October 2010

Quick facts

Lead sponsorShire
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment11
Start date20 February 2008
Primary completion22 October 2010
Estimated completion22 October 2010
Sites1 location across Denmark

Drugs / interventions tested

Conditions studied

Sponsor

Shire — full company profile →

Who can join

Adults 3 to 6, any sex, with Late Infantile Metachromatic Leukodystrophy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Level of Cerebrospinal Fluid (CSF) Sulfatide Secondary · Baseline until end of study (Week 139)

Level of CSF sulfatide measured at 6-month intervals in HGT-MLD-049 (NCT00681811).

GroupValue95% CI
100 U/kg HGT-1111 (Month 6)685.0± 522.79
200 U/kg HGT-1111 (Month 6)732.5± 545.06
100 U/kg HGT-1111 (Month 12)745.0± 525.12
200 U/kg HGT-1111 (Month 12)1150.0± 676.39
100 U/kg HGT-1111 (Month 18)700.0± 526.78
200 U/kg HGT-1111 (Month 18)850.0± 491.81
100 U/kg HGT-1111 (Month 24)900.0± NA
200 U/kg HGT-1111 (Month 24)837.5± 441.94
Level of White Matter Metabolites Secondary · Baseline until end of study (Week 139)

Level of white matter metabolites \[N-acetyl Aspartate (NAA)\] measured at 6-month intervals in HGT-MLD-049 (NCT00681811).

GroupValue95% CI
100 U/kg HGT-1111 (Month 6)0.528± 0.176
200 U/Kg-HGT-1111(Month 6)0.385± 0.237
100 U/kg- HGT-1111 (Month 12)0.598± 0.208
200 U/kg HGT-1111 (Month 12)0.470± 0.198
100 U/kg- HGT-1111(Month 18)0.510± 0.141
200 U/kg HGT-1111 (Month 18)0.805± 0.445
Score of Gross Motor Function Measurement (GMFM) Secondary · Baseline until end of study (Week 139)

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.

GroupValue95% CI
100 U/kg HGT-1111 (Month 6)16.8± 11.30
200 U/kg HGT-1111 (Month 6)9.2± 11.71
100 U/kg HGT-1111 (Month 12)15.6± 15.84
200 U/kg HGT-1111 (Month 12)8.7± 9.29
100 U/kg HGT-1111 (Month 18)16.8± 13.60
200 U/kg HGT-1111 (Month 18)9.0± 5.66
100 U/kg HGT-1111 (Month 24)14.5± 10.61
200 U/kg HGT-1111 (Month 24)13.0± 11.31
Days of Exposure to HGT-1111 Primary · Baseline until end of study (Week 139)

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.

GroupValue95% CI
100 U/kg HGT-1111644.7± 276.11
200 U/kg HGT-1111544.8± 397.27

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

100 U/kg HGT1111
Serious: 2/6 (33%)
Deaths:
200 U/kg HGT1111
Serious: 4/5 (80%)
Deaths:

Serious adverse events (12 terms)

ReactionSystem100 U/kg HGT1111200 U/kg HGT1111
EpilepsyNervous system disorders
PneumoniaInfections and infestations
Gastrooesophageal reflux diseaseGastrointestinal disorders
Lower respiratory track infectionInfections and infestations
PyrexiaGeneral disorders
Catheter bacteraemiaInfections and infestations
DiarrhoeaGastrointestinal disorders
Bronchitis acuteInfections and infestations
ConvulsionNervous system disorders
MalnutritionMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
Pseudomonas infectionInfections and infestations
Other adverse events (71 terms — click to expand)

ReactionSystem100 U/kg HGT1111200 U/kg HGT1111
PyrexiaGeneral disorders
NasopharyngitisInfections and infestations
FlushingVascular disorders
CoughRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
BronchitisInfections and infestations
Sleep disorderPsychiatric disorders
BronchospasmRespiratory, thoracic and mediastinal disorders
Pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders
EpilepsyNervous system disorders
Muscle spasticityNervous system disorders
Eyelid oedemaEye disorders
ConstipationGastrointestinal disorders
GastritisGastrointestinal disorders
Urticaria generalisedSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
Bronchitis acuteInfections and infestations
Eye infectionInfections and infestations
PharyngitisInfections and infestations
PallorVascular disorders
Disease progressionGeneral disorders
Adverse drug reactionGeneral disorders
Generalised oedemaGeneral disorders
Mental status changesPsychiatric disorders
PhimosisReproductive system and breast disorders
Joint dislocationInjury, poisoning and procedural complications
Feeding tube complicationInjury, poisoning and procedural complications
Blood alkaline phosphatase increasedInvestigations
Blood iron increasedInvestigations
Heart rate increasedInvestigations
Platelet count increasedInvestigations
Weight decreasedInvestigations
Increased bronchial secretionRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
AsthmaRespiratory, thoracic and mediastinal disorders
Respiratory distressRespiratory, thoracic and mediastinal disorders
DystoniaNervous system disorders
Depressed level of consciousnessNervous system disorders

Most-reported serious reactions: Epilepsy, Pneumonia, Gastrooesophageal reflux disease, Lower respiratory track infection, Pyrexia, Catheter bacteraemia, Diarrhoea, Bronchitis acute.

Data from ClinicalTrials.gov NCT00681811 adverse events section.

Sponsor's own description

This is a multi-center, open-label, extension study of patients with late infantile MLD who have previously completed clinical study HGT-MLD-048 (NCT00633139), defined as the completion of all Week 52 procedures. This group of patients will be offered ongoing treatment with HGT-1111 in this protocol. One infusion will be given every other week until the product is commercially available, the patient discontinues, or the study is terminated by the Sponsor, provided no safety issues have emerged.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches.
    Shaimardanova AA, Chulpanova DS, Solovyeva VV, Mullagulova AI, et al · · 2020 · cited 81× · PMID 33195324 · DOI 10.3389/fmed.2020.576221
  2. Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective.
    Beerepoot S, Nierkens S, Boelens JJ, Lindemans C, et al · · 2019 · cited 56× · PMID 31684987 · DOI 10.1186/s13023-019-1220-4
  3. Intravenous arylsulfatase A in metachromatic leukodystrophy: a phase 1/2 study.
    Í Dali C, Groeschel S, Moldovan M, Farah MH, et al · · 2021 · cited 16× · PMID 33332761 · DOI 10.1002/acn3.51254
  4. Treatment of adult metachromatic leukodystrophy model mice using intrathecal administration of type 9 AAV vector encoding arylsulfatase A.
    Miyake N, Miyake K, Sakai A, Yamamoto M, et al · · 2021 · cited 11× · PMID 34654893 · DOI 10.1038/s41598-021-99979-2
  5. Effects of sulfatide on peripheral nerves in metachromatic leukodystrophy.
    Farah MH, Dali CÍ, Groeschel S, Moldovan M, et al · · 2024 · cited 8× · PMID 38146590 · DOI 10.1002/acn3.51954
  6. Novel Therapeutic Approaches in Inherited Neuropathies: A Systematic Review.
    Hustinx M, Shorrocks AM, Servais L. · · 2023 · cited 4× · PMID 37376074 · DOI 10.3390/pharmaceutics15061626
  7. The effect of intrathecal recombinant arylsulfatase A therapy on structural brain magnetic resonance imaging in children with metachromatic leukodystrophy.
    Groeschel S, Beerepoot S, Amedick LB, Krӓgeloh-Mann I, et al · · 2024 · cited 1× · PMID 38321717 · DOI 10.1002/jimd.12706

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