A Phase 1/2, Multicenter, Open-Label Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL310 in Pediatric Participants with Hunter Syndrome

Recruiting

• Conditions: ysosomal Storage Diseases, Neurologic Manifestations, Nervous System Diseases; Hunter syndrome; mucopolysaccharidosis type II (MPS II); 10027424

• Registration Number: NL-OMON54074
• Lead Sponsor: Denali Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 2

Inclusion Criteria

- Confirmed diagnosis of MPS II
- Cohort A: Participants aged >= 5 to <=10 years with neuronopathic MPS II (nMPS
II)
- Cohort B: Participants aged >= 1 to <=18 years with non-neuronopathic MPS
II (nnMP II), neuronopathic MPS II, or unknown phenotype
- Cohort C: Participants aged <4 years with neuronopathic MPS II (this cohort
can include participants >=4 years of age if participant is a blood relative
with the same genetic mutation as participant >= 4 to <=18 years of age who will
be enrolled in the study)
- Cohort D: Participants aged <=18 years with nMPS II and nnMPS II and
preexisting hepatomegaly who have never taken standard - of - care ERT
- Cohort E: Neuronopathic MPS II Participants aged >= 6 years at screening,
nnMPS II participants < 6 or >=17 years at screening, and nMPS II participants
>= 1 to <=18 years at screening who have completed at least 48 weeks in Study
DNLI-E-0001
- For participants receiving intravenous iduronate 2-sulfatase (IDS) ERT,
tolerated a minimum of 4 months of therapy during the period immediately prior
to screening.

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
- Use of any CNS-targeted MPS II ERT within 3 months before study start for
participants aged >=5 years, and within 6 months before study start for
participants aged <5 years.
- Use of IDS gene therapy or stem cell therapy at any time
- Clinically significant thrombocytopenia, other clinically significant
coagulation abnormality, or significant active bleeding, or required treatment
with an anticoagulant or more than two antiplatelet agents
- Contraindication for lumbar punctures
- Have a clinically significant history of stroke, status epilepticus, head
trauma with loss of consciousness, or any CNS disease that is not MPS
II-related within 1 year of screening
- Have had a ventriculoperitoneal (VP) shunt placed, or any other brain
surgery, or have a clinically significant VP shunt malfunction within 30 days
of screening
- Have any clinically significant CNS trauma or disorder that, in the opinion
of the investigator, may interfere with assessment of study endpoints or make
participation in the study unsafe
- Have clinically significant anemia

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Incidence and severity of treatment-emergent adverse events (TEAEs) at 24<br /><br>weeks, 104 weeks, 261 weeks, and across study<br /><br>- Change from baseline in safety laboratory values, vital sign measurements,<br /><br>electrocardiogram (ECG) findings, urine total glycosaminoglycan (GAG) levels,<br /><br>and physical and neurological assessments at 24 weeks, 104 weeks, 261 weeks,<br /><br>and across study<br /><br>- Incidence and severity of infusion-related reactions (IRRs) at 24 weeks, 104<br /><br>weeks, 261 weeks, and across study<br /><br>- Change from baseline in concomitant medication at 24 weeks, 104 weeks, 261<br /><br>weeks, and across study</p><br>