A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 in Healthy Volunteers

Sponsor
Denali Therapeutics Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04268784
Collaborator
(none)
96
1
2
17.4
5.5

Study Details

Study Description

Brief Summary

This is a Phase 1 study carried out at a single site in 88 healthy male subjects and healthy female subjects of non childbearing potential to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of DNL343.

Condition or Disease Intervention/Treatment Phase
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
Actual Enrollment :
96 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Single-Center, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 In Healthy Volunteers
Actual Study Start Date :
Feb 20, 2020
Actual Primary Completion Date :
Aug 3, 2021
Actual Study Completion Date :
Aug 3, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: DNL343

Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses

Drug: DNL343
Single and repeating oral dose(s)

Placebo Comparator: Placebo

Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses

Drug: Placebo
Single and repeating oral dose(s)

Outcome Measures

Primary Outcome Measures

  1. Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs [Up to 20 days]

  2. PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma [Up to 20 days]

  3. PK parameter: The area under the concentration-time curve from zero to 12 or 24 hours for twice daily (BID) or once daily (QD) dosing, respectively (AUC0-τ) of DNL343 in plasma [Up to 20 days]

  4. PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma [Up to 20 days]

  5. PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL343 in plasma [Up to 20 days]

  6. PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma [Up to 20 days]

  7. PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma [Up to 20 days]

Secondary Outcome Measures

  1. PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48) [Up to 20 days]

  2. PK parameter: Estimation of renal clearance (CLR) [Up to 20 days]

  3. PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF) [Up to 20 days]

  4. The PD of DNL343 in blood as measured by percent reduction of integrated stress response (ISR) protein levels measured by enzyme-linked immunosorbent assay (ELISA) [Up to 20 days]

  5. The PD of DNL343 in blood as measured by percent reduction in ISR gene expression levels measured by quantitative polymerase chain reaction (qPCR) [Up to 20 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Key Inclusion Criteria:
  • Women of non-childbearing potential and men; aged 18-50 years, inclusive

  • BMI 18-32 kg/m², inclusive, and body weight of at least 50 kg

Key Exclusion Criteria:
  • History of clinically significant neurologic, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders

Contacts and Locations

Locations

Site City State Country Postal Code
1 Centre for Human Drug Research (CHDR) Leiden South Holland Netherlands 2333

Sponsors and Collaborators

  • Denali Therapeutics Inc.

Investigators

  • Study Director: Richard Tsai, MD, Denali Therapeutics Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Denali Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT04268784
Other Study ID Numbers:
  • DNLI-F-0001
  • 2019-004027-21
First Posted:
Feb 13, 2020
Last Update Posted:
Feb 7, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No

Study Results

No Results Posted as of Feb 7, 2022