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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: DNL151; Drug: Placebo

• Registration Number: NCT04557800
• Lead Sponsor: Denali Therapeutics Inc.

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.

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 Timeline

• Study Start: 2017-11-16
• Study First Submitted: 2020-09-10
• Study First Submitted QC: 2020-09-15
• Study First Posted: 2020-09-22
• Primary Completion: 2021-02-19
• Study Completion: 2021-02-19
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-18
• Last Update Posted: 2022-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 186

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
DNL151	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	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)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (2)

PRA Health Sciences, Van Swietenlaan; 🇳🇱 Groningen, Netherlands

Centre for Human Drug Research; 🇳🇱 Leiden, South Holland, Netherlands