Trial record 1 of 1 for:
DNL310
A Study of DNL310 in Pediatric Participants With Hunter Syndrome
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| ClinicalTrials.gov Identifier: NCT04251026 |
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Recruitment Status :
Recruiting
First Posted : January 31, 2020
Last Update Posted : May 14, 2021
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Sponsor:
Denali Therapeutics Inc.
Information provided by (Responsible Party):
Denali Therapeutics Inc.
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Brief Summary:
This is a multicenter, multiregional, open-label study to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL310, an investigational central nervous system (CNS)-penetrant enzyme replacement therapy (ERT), designed to treat both the peripheral and CNS manifestations of Mucopolysaccharidosis type II (MPS II; Hunter syndrome).
The study has three cohorts:Cohort A will enroll participants with neuronopathic MPS II aged 5 to 10 years; Cohort B will enroll participants with MPS II, either neuronopathic or non-neuronopathic, aged 2 to 18 years; and Cohort C will enroll participants with neuronopathic MPS II aged ≥2 and <4 (Cohort C can include nMPS II participants ≥4 if the participant is a sibling of a participant aged ≥2 and <4).
Participants, whose physicians feel they are deriving benefit, will have the opportunity to be reconsented into a safety extension for continued evaluation.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Mucopolysaccharidosis II | Drug: DNL310 | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 30 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2, Multicenter, Open-Label Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL310 in Pediatric Participants With Hunter Syndrome |
| Actual Study Start Date : | July 16, 2020 |
| Estimated Primary Completion Date : | March 2024 |
| Estimated Study Completion Date : | March 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Mucopolysaccharidosis type II
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort A
Dose escalation followed by a consistent dose level in participants with neuronopathic MPS II
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Drug: DNL310
Intravenous weekly administration |
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Experimental: Cohort B
A consistent dose level in participants with non-neuronopathic MPS II, neuronopathic MPS II, or unknown phenotype followed by dose escalation in some participants.
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Drug: DNL310
Intravenous weekly administration |
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Experimental: Cohort C
A consistent dose level in participants with neuronopathic MPS II
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Drug: DNL310
Intravenous weekly administration |
Primary Outcome Measures :
- Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: 24 weeks ]
- Incidence and severity of infusion-related reactions (IRRs) [ Time Frame: 24 weeks ]
- Change from baseline in urine total glycosaminoglycan (GAG) concentrations [ Time Frame: 24 weeks ]
- Change from baseline in concomitant medications [ Time Frame: 24 weeks ]
Secondary Outcome Measures :
- Change from baseline in cerebrospinal fluid (CSF) of heparan sulfate [ Time Frame: 24 weeks ]
- PK parameter: Maximum observed concentration (Cmax) of DNL310 in serum [ Time Frame: 24 weeks ]
- PK parameter: Trough concentration (Cmin) of DNL310 in serum [ Time Frame: 24 weeks ]
- PK parameter: Time to maximum observed concentration (tmax) of DNL310 in serum [ Time Frame: 24 weeks ]
- PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of DNL310 in serum [ Time Frame: 24 weeks ]
- PK parameter: Area under the concentration-time curve from time zero to infinity (AUC∞) of DNL310 in serum [ Time Frame: 24 weeks ]
- PK parameter: Area under the concentration-time curve over a dosing interval (AUCτ) of DNL310 in serum [ Time Frame: 24 weeks ]
- PK parameter: Apparent terminal elimination half-life (t½) of DNL310 in serum [ Time Frame: 24 weeks ]
- Characterization of immunogenicity of DNL310 in serum, as measured by the incidence of anti-drug antibodies (ADAs) relative to baseline [ Time Frame: 24 weeks ]
- Change from baseline in urine concentration of heparan sulfate (HS) [ Time Frame: 24 weeks ]
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| Ages Eligible for Study: | 2 Years to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Confirmed diagnosis of MPS II
- Cohort A: Participants aged 5 to 10 years with neuronopathic MPS II
- Cohort B: Participants aged 2 to 18 years with non-neuronopathic MPS II, neuronopathic MPS II, or unknown phenotype
- Cohort C: Participants aged ≥2 to <4 years with neuronopathic MPS II (this cohort can include participants ≥4 years of age if participant is a sibling of a participant ≥2 to <4 years of age)
- For participants receiving intravenous iduronate 2-sulfatase (IDS) ERT, tolerated a minimum of 4 months of therapy during the period immediately prior to screening.
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
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04251026
Contacts
| Contact: Clinical Trials at Denali Therapeutics | Email: | clinical-trials@dnli.com |
Locations
| United States, California | |
| UCSF Benioff Children's Hospital | Recruiting |
| Oakland, California, United States, 94609 | |
| Contact: Huong Phan 510-428-3885 ext 5917 huong.phan@ucsf.edu | |
| Contact paul.harmatz@ucsf.edu | |
| Principal Investigator: Paul Harmatz, MD | |
| United States, Illinois | |
| Ann & Robert H. Lurie Children's Hospital of Chicago | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Contact: Marian Krasowski 312-227-8953 mkrasowski@luriechildrens.org | |
| Principal Investigator: Barbara Burton, MD | |
| United States, North Carolina | |
| UNC Children's Research Institue | Recruiting |
| Chapel Hill, North Carolina, United States, 27514 | |
| Contact: Chen Zhu 919-966-1447 czhu@email.unc.edu | |
| Contact muenzer@med.unc.edu | |
| Principal Investigator: Joseph Muenzer, MD | |
| United States, Pennsylvania | |
| UPMC | Children's Hospital of Pittsburgh | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15224 | |
| Contact: Alyssa Aburachis 412-692-6340 alyssa.aburachis@chp.edu | |
| Contact maria.escolar@chp.edu | |
| Principal Investigator: Maria Escolar, MD | |
Sponsors and Collaborators
Denali Therapeutics Inc.
Investigators
| Study Director: | Anna Bakardjiev, MD | Denali Therapeutics |
| Responsible Party: | Denali Therapeutics Inc. |
| ClinicalTrials.gov Identifier: | NCT04251026 |
| Other Study ID Numbers: |
DNLI-E-0002 2019-004909-27 ( EudraCT Number ) |
| First Posted: | January 31, 2020 Key Record Dates |
| Last Update Posted: | May 14, 2021 |
| Last Verified: | May 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Denali Therapeutics Inc.:
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MPS II Hunter Syndrome nMPS II |
Additional relevant MeSH terms:
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Mucopolysaccharidosis II Mucopolysaccharidoses Carbohydrate Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Lysosomal Storage Diseases Mucinoses Connective Tissue Diseases |
Metabolic Diseases Mental Retardation, X-Linked Intellectual Disability Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Genetic Diseases, X-Linked Heredodegenerative Disorders, Nervous System |