An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007

Denali Therapeutics

Status and phase: Invitation-only; Phase 3; Phase 2

Conditions: Mucopolysaccharidosis II

Treatments: Drug: tividenofusp alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT06075537

2023-503837-23 (Other Identifier)

DNLI-E-0008

Details and patient eligibility

About

This is a multiregional open-label extension (OLE) to assess the safety, tolerability, and efficacy of long-term treatment with tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant intravenous (IV) enzyme replacement therapy (ERT) for Hunter syndrome (MPS II). Participants who complete at least through the Week 49 visit in Study DNLI-E-0002 and do not discontinue study intervention early and participants who complete Study DNLI-E-0007 will be enrolled in this OLE. All participants will receive DNL310 for up to 5 years from the time of entry in this OLE. Participants, site staff, and the Sponsor will remain blinded to the original treatment assignment for participants entering this OLE from Study DNLI-E-0007.

Enrollment: 99 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early
• For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS II participants and 48 weeks in Cohort B for nnMPS II participants

Key Exclusion Criteria:

• Unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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99 participants in 7 patient groups

Cohort A2

Experimental group

Description:

Participants with nMPS II, aged ≥5 to ≤10 years

Treatment:

Drug: tividenofusp alfa

Cohort B2

Experimental group

Description:

Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years

Treatment:

Drug: tividenofusp alfa

Cohort C2

Experimental group

Description:

Participants with nMPS II, aged \<4 years

Treatment:

Drug: tividenofusp alfa

Cohort D2

Experimental group

Description:

Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT

Treatment:

Drug: tividenofusp alfa

Cohort E2

Experimental group

Description:

Participants with nMPS II, aged ≥6 years; participants with nnMPS II, aged \<6 or ≥17 years; or participants with nMPS II, aged ≥1 to ≤18 years, with a history of prior HSCT or gene therapy and have completed at least 48 weeks in Study DNLI-E-0001

Treatment:

Drug: tividenofusp alfa

Cohort A7

Experimental group

Description:

Participants with nMPS II, aged ≥2 to \<6 years

Treatment:

Drug: tividenofusp alfa

Cohort B7

Experimental group

Description:

Participants with nnMPS II, aged ≥6 to \<17 years

Treatment:

Drug: tividenofusp alfa