NCT04268784

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
96

participants targeted

Target at P75+ for phase_1 healthy-volunteers

Timeline
Completed

Started Feb 2020

Longer than P75 for phase_1 healthy-volunteers

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 10, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 13, 2020

Completed
7 days until next milestone

Study Start

First participant enrolled

February 20, 2020

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 3, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 3, 2021

Completed
Last Updated

February 7, 2022

Status Verified

February 1, 2022

Enrollment Period

1.5 years

First QC Date

February 10, 2020

Last Update Submit

February 3, 2022

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (7)

  • Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs

    Up to 20 days

  • PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma

    Up to 20 days

  • 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

  • PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma

    Up to 20 days

  • 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

  • PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma

    Up to 20 days

  • PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma

    Up to 20 days

Secondary Outcomes (5)

  • PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48)

    Up to 20 days

  • PK parameter: Estimation of renal clearance (CLR)

    Up to 20 days

  • PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF)

    Up to 20 days

  • 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

  • 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

Study Arms (2)

DNL343

EXPERIMENTAL

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

Drug: DNL343

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

DNL343DRUG

Single and repeating oral dose(s)

DNL343
PlaceboDRUG

Single and repeating oral dose(s)

Placebo

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre for Human Drug Research (CHDR)

Leiden, South Holland, 2333, Netherlands

Location

Study Officials

  • Richard Tsai, MD

    Denali Therapeutics Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 10, 2020

First Posted

February 13, 2020

Study Start

February 20, 2020

Primary Completion

August 3, 2021

Study Completion

August 3, 2021

Last Updated

February 7, 2022

Record last verified: 2022-02

Data Sharing

IPD Sharing
Will not share

Locations

NL(1)