Health TrialsbyHealthPanel

A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)

ConditionMucopolysaccharidosis II
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age2-25
SponsorDenali Therapeutics Inc.

About this trial

This is a Phase 2/3, multiregional, two-arm, double-blind, randomized, active (standard-of-care)-controlled study of the efficacy and safety of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme-replacement therapy (ERT) for mucopolysaccharidosis type II (MPS II).

Participants may also qualify to enter an open-label treatment phase with DNL310 or idursulfase based on pre-specified criteria.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants aged ≥2 to <6 years (Cohort A) or ≥6 to <26 years (Cohort B)

Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)

Have no history of treatment with enzyme replacement therapy (ERT) OR not have received continuous ERT for 4 months prior to screening OR be on maintenance ERT and have tolerated idursulfase for a minimum of 4 months prior to screening

Disqualifiers

Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay

Previously received an iduronate 2-sulfatase (IDS) gene therapy or stem cell therapy

Received any CNS-targeted MPS ERT within 6 months prior to screening

Have a contraindication for lumbar punctures and/or magnetic resonance imaging (MRI)

Trial design

Design model

Parallel

Treatments tested in this trial

  • tividenofusp alfa

    Drug

    Intravenous repeating dose

  • idursulfase

    Drug

    Intravenous repeating dose

Treatment groups

63 Participants
are divided into 3 treatment groups
Group A: Cohort A: Participants with nMPS IIExperimental treatment 2 interventions
Group B: Cohort B: Participants with nnMPS IIExperimental treatment 2 interventions
Group C: Open-label Treatment PhaseExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)

Time frame
24 weeks
2

Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)

Time frame
96 weeks

Secondary outcomes

1

Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)

Time frame
96 weeks
2

Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC; Cohort A only)

Time frame
96 weeks
3

Change from baseline in serum neurofilament light chain (NfL) (Cohort A only)

Time frame
96 weeks
4

Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)

Time frame
48 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Denali Therapeutics Inc.

Lead sponsor

Source ClinicalTrials.gov
Apply now