NCT04557800

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
186

participants targeted

Target at P75+ for phase_1 healthy-volunteers

Timeline
Completed

Started Nov 2017

Longer than P75 for phase_1 healthy-volunteers

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 16, 2017

Completed
2.8 years until next milestone

First Submitted

Initial submission to the registry

September 10, 2020

Completed
12 days until next milestone

First Posted

Study publicly available on registry

September 22, 2020

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 19, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 19, 2021

Completed
Last Updated

March 7, 2022

Status Verified

February 1, 2022

Enrollment Period

3.3 years

First QC Date

September 10, 2020

Last Update Submit

February 18, 2022

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (7)

  • 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 (2)

  • 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

Study Arms (2)

DNL151

EXPERIMENTAL

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)

Drug: DNL151

Placebo

PLACEBO COMPARATOR

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)

Drug: Placebo

Interventions

DNL151DRUG

oral dose(s)

DNL151
PlaceboDRUG

oral dose(s)

Placebo

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Centre for Human Drug Research

Leiden, South Holland, 2333, Netherlands

Location

PRA Health Sciences, Van Swietenlaan

Groningen, 9728, Netherlands

Location

Related Publications (1)

  • 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: 40680102DERIVED

MeSH Terms

Interventions

DNL151

Study Officials

  • Andres Cruz-Herranz

    Denali Therapeutics Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 10, 2020

First Posted

September 22, 2020

Study Start

November 16, 2017

Primary Completion

February 19, 2021

Study Completion

February 19, 2021

Last Updated

March 7, 2022

Record last verified: 2022-02

Locations

NL(2)