E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mucopolysaccharidosis Type II [MPS II] |
Mucopolisaccaridosi di Tipo II |
|
E.1.1.1 | Medical condition in easily understood language |
Hunter Syndrome |
Sindrome di Hunter |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056889 |
E.1.2 | Term | Mucopolysaccharidosis II |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To evaluate the CNS activity of DNL310 vs idursulfase as measured by the cerebrospinal fluid (CSF) concentration of heparan sulfate (HS) in participants with the neuronopathic form of mucopolysaccharidosis type II (nMPS II) 2. To evaluate the clinical CNS efficacy of DNL310 vs idursulfase on adaptive behavior as assessed by the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3), in nMPS II participants |
1. Valutare l'attività sul SNC di DNL310 rispetto a idursulfasi come misurata dalla concentrazione di solfato di eparano (HS) nel liquido cerebrospinale (CSF) in partecipanti con la forma neuronopatica della mucopolisaccaridosi di tipo II (nMPS II) 2. Valutare l'efficacia clinica sul SNC di DNL310 rispetto a idursulfasi sul comportamento adattivo come valutato dalla Scala di comportamento adattivo Vineland, terza edizione (Vineland-3), comportamento adattivo composito (ABC) nei partecipanti nMPS II |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the clinical CNS efficacy of DNL310 vs idursulfase on neurocognitive development, as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), in nMPS II participants 2. To evaluate the clinical efficacy of DNL310 vs idursulfase on physical endurance as measured by the Six-Minute Walk Test (6MWT) in participants with the nnMPS II 3. To evaluate the onset and durability of peripheral efficacy of DNL310 vs idursulfase as measured by the urine concentration of total glycosaminoglycans (GAGs) by a massspectrometry–based detection method in nMPS II and nnMPS II participants 4. To evaluate the efficacy of DNL310 vs idursulfase on liver volume and spleen volume as measured by MRI in nMPS II and nnMPS II participants 5. To evaluate the parent's/caregiver's assessment of efficacy of DNL310 vs idursulfase as measured by the Parent/Caregiver Global Impression of Change (CaGI-C) in nMPS II and nnMPS II participants |
Fare Riferimento alla Sinossi per Obiettivi secondari in Italiano |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants aged =2 to <6 years (Cohort A) or =6 to <17 years (Cohort B)
2. Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)
3. Be on maintenance enzyme replacement therapy (ERT) and have tolerated idursulfase for a minimum of 4 months prior to screening |
1. Partecipanti maschi e femmine di età compresa tra >= 2 e < 6 anni (Coorte A) o >= 6 e < 17 anni (Coorte B)
2. Confermata diagnosi di MPS II (Per Coorte A nMPS II; per Coorte B nnMPS II)
3. Tutti i partecipanti devono aver ricevuto terapia ERT di mantenimento e aver tollerato un minimo di 4 mesi di terapia con idursulfasi (Elaprase) durante il periodo immediatamente precedente allo screening. |
|
E.4 | Principal exclusion criteria |
1. Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay
2. Previously received an IDS gene therapy or stem cell therapy
3. Received any CNS-targeted MPS ERT within 6 months prior to screening
4. Have a contraindication for lumbar punctures and/or magnetic resonance imaging (MRIs)
5. Participated in any other investigational drug study or used an investigational drug within 60 days prior to screening or intend to receive another investigational drug during the study |
1. Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay
2. Previously received an IDS gene therapy or stem cell therapy
3. Received any CNS-targeted MPS ERT within 6 months prior to screening
4. Have a contraindication for lumbar punctures and/or magnetic resonance imaging (MRIs)
5. Participated in any other investigational drug study or used an investigational drug within 60 days prior to screening or intend to receive another investigational drug during the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Percent change from baseline in CSF HS concentration at Week 24 (Cohort A only)
2. Change from baseline in the Vineland-3 at Week 96 (Cohort A only) |
1. Variazione percentuale dal basale nella concentrazione di HS nel CSF alla Settimana 24 (solo Coorte A)
2. Variazione dal basale nella Vineland-3 ABC alla Settimana 96 (solo Coorte A) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Week 24 2. Week 96 |
1. Settimana 24 2. Settimana 96 |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at Week 96 (Cohort A only) 2. Change from baseline in distance walked in the 6MWT at Week 48 (Cohort B only) 3. Percent change from baseline in the sum of urine HS and DS concentrations at Week 48 (Cohorts A and B) 4. a) Liver volume within the normal range (normal vs abnormal) as measured by MRI at Week 48 (Cohorts A and B) b) Spleen volume within the normal range (normal vs abnormal) as measured by MRI at Week 48 (Cohorts A and B) 5. Improvement in CaGI-C Overall MPS II at Week 48 (Cohorts A and B) |
1. Variazione dal basale nel punteggio cognitivo grezzo BSID-III alla Settimana 96 (solo coorte A) 2. Variazione dal basale nella distanza percorsa (metri) nel 6MWT alla Settimana 48 (solo Coorte B) 3. Variazione percentuale dal basale nella somma delle concentrazioni di HS e dermatan solfato (DS) nelle urine alla Settimana 24 (Coorti A e B) 4. a) Volume del fegato entro il range di normalità (normale vs anormale) come misurato da RMI alla Settimana 48 (Coorti A e B) b) Volume della milza entro il range di normalità (normale vs anomalo) misurato da RMI alla Settimana 48 (Coorti A e B) 5. Miglioramento nella CaGI-C globale per MPS II (definito come molto migliorata o poco migliorata) alla Settimana 48 (Coorti A e B) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 96 2. Week 48 3. Week 48 4. a) Week 48 b) Week 48 5. Week 48 |
1. Week 96 2. Week 48 3. Week 48 4. a) Week 48 b) Week 48 5. Week 48 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Immunogenicity |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Canada |
Colombia |
Mexico |
United States |
France |
Sweden |
Netherlands |
Spain |
Czechia |
Germany |
Italy |
Belgium |
Turkey |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of this study is defined as the date on which LPLV occurs. LPLV is expected to occur approximately 2 years after the last participant is enrolled if the last participant is in Cohort A, or approximately 1 year after the last participant is enrolled if the last participant is in Cohort B, whichever has the later last study visit assessment. |
The end of this study is defined as the date on which LPLV occurs. LPLV is expected to occur approximately 2 years after the last participant is enrolled if the last participant is in Cohort A, or approximately 1 year after the last participant is enrolled if the last participant is in Cohort B, whichever has the later last study visit assessment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |