A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL151 in Healthy Volunteers

NCT04557800 — Phase 1, Completed, 186 participants, Denali Therapeutics Inc.

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A Phase 1, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Of DNL151 in Healthy Volunteers

Registry	NCT04557800
Status	Completed
Phase	Phase 1
Study type	Interventional; randomized, sequential, masking: double, treatment
Enrollment	186 (Actual)
Sponsor	Denali Therapeutics Inc. (Industry)
Conditions	Healthy Volunteers
Interventions	DNL151, Placebo (Drug)
Dates	start 2017-11-16, primary completion 2021-02-19, completion 2021-02-19, first posted 2020-09-22, last updated 2022-03-07
Locations	2 sites in Netherlands

-Summary

This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD), and 28-day safety study of orally administered DNL151 in healthy volunteers.

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+Detailed description

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under Section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by Sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

+Arms and interventions

Arm	Type	Interventions	Description
DNL151	Experimental	Drug: DNL151	Part A: Single-ascending dose cohorts; Part B: Multiple-ascending dose cohorts (10 days); Part C: Single-dose cohort; Part D: Additional multiple-dose cohort (28 days); Part E Multiple-ascending dose cohorts (14 days)
Placebo	Placebo comparator	Drug: Placebo	Part A: Single-ascending dose cohorts; Part B: Multiple-ascending dose cohorts (10 days); Part C: Single-dose cohort; Part D: Additional multiple-dose cohort (28 days); Part E Multiple-ascending dose cohorts (14 days)

DNL151 (Drug): oral dose(s)
Placebo (Drug): oral dose(s)

+Outcome measures

Primary outcomes

Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs [Up to 42 days]
PK parameter: Maximum observed concentration (Cmax) of DNL151 in plasma [Up to 42 days]
PK parameter: Time to maximum observed concentration (Tmax) of DNL151 in plasma [Up to 42 days]
PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL151 in plasma (single dosing only) [Up to 42 days]
PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL151 in plasma [Up to 42 days]
PK parameter: The area under the concentration-time curve over a dosing interval (AUC0-τ) of DNL151 in plasma (multiple dosing only) [Up to 42 days]
PK parameter: Apparent terminal elimination half-life (t1/2) of DNL151 in plasma [Up to 42 days]

Secondary outcomes

Concentration of DNL151 in cerebrospinal fluid (CSF) (following selected single and multiple doses) [Up to 13 days]
The pharmacodynamics of DNL151 in whole blood as measured by the percent change from baseline in pS935 [Up to 42 days]

+Eligibility

Sex: All, ages: 18 Years to 75 Years, accepts healthy volunteers

Key Inclusion Criteria:

* Body mass index 18.5 to 35.0 kg/m², inclusive, and body weight of at least 50.0 kg at screening
* In good health, determined by no clinically significant findings from medical history, physical examination, and vital sign measurements
* Women of non-childbearing potential and men using contraceptive measures

Key Exclusion Criteria:

* History of clinically significant hematological, renal, pancreatic, gastrointestinal, hepatic, cardiovascular, metabolic, endocrine, immunological, allergic disease, or other major disorders
* History of asthma, chronic obstructive pulmonary disease, or emphysema
* Clinically significant neurologic disorder
* History of stomach or intestinal surgery or resection
* History of malignancy

+Locations (2)

Facility	City	Country	Status
Centre for Human Drug Research	Leiden, South Holland	Netherlands
PRA Health Sciences, Van Swietenlaan	Groningen	Netherlands

+Publications

Results publication: Joshi D, Kulkarni M, Parekh P, Shah S, Greig NH, Acharya S. Targeting protein kinases in Parkinson's disease: the emerging role of phytoconstituents. Nutr Neurosci. 2025 Dec;28(12):1532-1563. doi: 10.1080/1028415X.2025.2531356. Epub 2025 Jul 18. PMID 40680102

+Investigators

Andres Cruz-Herranz, Study director, Denali Therapeutics Inc.

+Funding

NIH grants: 2017