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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04268784
Recruitment Status : Completed
First Posted : February 13, 2020
Last Update Posted : February 7, 2022
Sponsor:
Information provided by (Responsible Party):
Denali Therapeutics Inc.

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
Healthy Volunteers Drug: DNL343 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.).

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Study Type : Interventional  (Clinical Trial)
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 : February 20, 2020
Actual Primary Completion Date : August 3, 2021
Actual Study Completion Date : August 3, 2021

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)




Primary Outcome Measures :
  1. Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 20 days ]
  4. PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma [ Time Frame: 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 [ Time Frame: Up to 20 days ]
  6. PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma [ Time Frame: Up to 20 days ]
  7. PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma [ Time Frame: 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) [ Time Frame: Up to 20 days ]
  2. PK parameter: Estimation of renal clearance (CLR) [ Time Frame: Up to 20 days ]
  3. PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to 20 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04268784


Locations
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Netherlands
Centre for Human Drug Research (CHDR)
Leiden, South Holland, Netherlands, 2333
Sponsors and Collaborators
Denali Therapeutics Inc.
Investigators
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Study Director: Richard Tsai, MD Denali Therapeutics Inc.
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Responsible Party: Denali Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04268784    
Other Study ID Numbers: DNLI-F-0001
2019-004027-21 ( EudraCT Number )
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: February 7, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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