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

• ClinicalTrials.gov Identifier: NCT04557800
• Recruitment Status: Completed
• First Posted: September 22, 2020
• Last Update Posted: March 7, 2022
• Sponsor: Denali Therapeutics Inc.
• Information provided by (Responsible Party): Denali Therapeutics Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: DNL151; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Of DNL151 in Healthy Volunteers
• Actual Study Start Date: November 16, 2017
• Actual Primary Completion Date: February 19, 2021
• Actual Study Completion Date: February 19, 2021

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Netherlands

Centre for Human Drug Research

Leiden, South Holland, Netherlands, 2333

PRA Health Sciences, Van Swietenlaan

Groningen, Netherlands, 9728

Sponsors and Collaborators

Denali Therapeutics Inc.

Investigators

• Study Director: Andres Cruz-Herranz; Denali Therapeutics Inc.

More Information

• Responsible Party: Denali Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT04557800
• Other Study ID Numbers: DNLI-C-0001; 2017-003730-82 ( EudraCT Number )
• First Posted: September 22, 2020
• Last Update Posted: March 7, 2022
• Last Verified: February 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No