Mucopolysaccharidosis Type II [MPS II] MedDRA version: 20.1 Level: PT Classification code 10056889 Term: Mucopolysaccharidosis II System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: DNL310
Product Code: DNL310
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: DNL310
Current Sponsor code: DNL310 Drug Substance. Also referred to as: ETV
Sponsors
Denali Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants aged =2 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Have a documented pathogenic or likely pathogenic variants that are knwon to cause developmental delay or decline, cognitivedysfunction, seizures, or other significant CNS discorders. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: 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 CNS efficacy of DNL310 vs idursulfase on adaptive behavior as assessed by the Vineland-3 ABC in nMPS II participants 3. To evaluate the efficacy of DNL310 vs idursulfase on neuronal injury in nMPS 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;Primary end point(s): 1. Percent change from baseline in CSF HS concentration at Week 24 (Cohort A) 2. Change from baseline in the Vineland-3 ABRS-8 at Week 96 (Cohort A);Timepoint(s) of evaluation of this end point: 1. Week 24 2. Week 96 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 the Vineland-3 ABC at Week 96 (Cohort A only) 3. Change from baseline in serum NfL at Week 96 (Cohort A only) 4. Change from baseline in distance walked (meters) in the 6MWT at Week 48 (Cohort B only) 5. Percent change from baseline in the sum of urine HS and DS concentrations at Week 48 (Cohorts A and B);Timepoint(s) of evaluation of this end point: 1. Week 96 2. Week 96 3. Week 96 4. Week 48 5. Week 48 | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Colombia, Czechia, Czech Republic, France, Germany, Italy, Mexico, Netherlands, Spain, Sweden, Türkiye, United Kingdom, United States
Contacts
Public ContactClinical Trials Group at Denali
Denali Therapeutics Inc.
Outcome results
None listed