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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: DNL151; Drug: Placebo

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.).

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728
    • PRA Health Sciences, Van Swietenlaan
  • South Holland
    • Leiden, South Holland, Netherlands, 2333
      • Centre for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: DNL151; oral dose(s)
Placebo Comparator: 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)	Drug: Placebo; oral dose(s)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Denali Therapeutics Inc.
• Investigators: Study Director: Andres Cruz-Herranz, Denali Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2017
• Primary Completion (Actual): February 19, 2021
• Study Completion (Actual): February 19, 2021

Study Registration Dates

• First Submitted: September 10, 2020
• First Submitted That Met QC Criteria: September 15, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 7, 2022
• Last Update Submitted That Met QC Criteria: February 18, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: DNLI-C-0001; 2017-003730-82 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No