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DNL343

Phase 1

Amyotrophic Lateral Sclerosis | Small molecule | Neurology |Denali Therapeutics Inc.|Last Updated: Sep 19, 2024

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment29

FDA Designations

No designations recorded

Clinical trial landscape

DNL343 · 4 trials · 2 indications

Phase 1 4
NCT06281158A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-DNL343 Following a Single Oral Dose in Healthy Male ParticipantsHealthy Volunteers
COMPLETED7 Analytics
NCT05006352A Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral SclerosisAmyotrophic Lateral Sclerosis
COMPLETED29 Analytics
NCT04581772A Study to Evaluate the Bioavailability and Safety of DNL343 in Healthy VolunteersHealthy Volunteers
COMPLETED31 Analytics
NCT04268784A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 in Healthy VolunteersHealthy Volunteers
COMPLETED96 Analytics
PHASE1COMPLETED
A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-DNL343 Following a Single Oral Dose in Healthy Male Participants
Healthy VolunteersUnlock trial analytics
PHASE1COMPLETED
A Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis
Amyotrophic Lateral SclerosisUnlock trial analytics
PHASE1COMPLETED
A Study to Evaluate the Bioavailability and Safety of DNL343 in Healthy Volunteers
Healthy VolunteersUnlock trial analytics
PHASE1COMPLETED
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 in Healthy Volunteers
Healthy VolunteersUnlock trial analytics

Study Endpoints

Primary Endpoints

PK Parameter: AUC0-∞
28 days

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

PK Parameter: AUC0-tlast
28 days

Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-tlast) of DNL343 in plasma

PK Parameter: Cmax
28 days

Maximum observed concentration (Cmax) of DNL343 in plasma

PK Parameter: Tmax
28 days

Time to maximum observed concentration (Tmax) of DNL343 in plasma

PK Parameter: t1/2
28 days

Terminal elimination half-life (t1/2) of DNL343 in plasma

Total radioactivity in plasma and whole blood
28 days
Total radioactivity in blood-to-plasma ratio
28 days
Extent and rate of recovery of total radioactivity in urine and feces
28 days
Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period
28 Days
PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma
Up to 15 days
PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma
Up to 15 days
PK Parameter: Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of DNL343 in plasma
Up to 15 days
PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma
Up to 15 days
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 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: 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: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma
Up to 20 days

Secondary Endpoints

PK Parameter: AUC0-∞
28 days
PK Parameter: AUC0-tlast
28 days
PK Parameter: Cmax
28 days
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
14C-DNL343EXPERIMENTAL -
DNL343 (High Dose)EXPERIMENTAL -
DNL343 (Low Dose)EXPERIMENTAL -
PlaceboPLACEBO_COMPARATOR -
Cohort AEXPERIMENTAL -
Cohort BEXPERIMENTAL -
Cohort CEXPERIMENTAL -
DNL343EXPERIMENTALCohort A: Single-ascending dose; Cohort B: Multiple-ascending doses

Interventions

NameTypeDescription
[14C]-DNL343DRUGSingle dose
DNL343DRUGOral repeating dose
PlaceboDRUGOral repeating dose
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Eligibility Criteria

Age Range18 Years to 65 Years
SexMALE
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * Males, aged between 18 to 65 years, inclusive * Body mass index between 18.0 and 32.0 kg/m2 * In good health * When engaging in sex with a woman of child bearing potential, both the male participant and his female partner must use highly effective contraception * History of a ...

Countries:United StatesNetherlandsNew Zealand
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Frequently asked questions about DNL343

What is DNL343 used for?

DNL343 is an investigational small molecule being studied for Amyotrophic Lateral Sclerosis (ALS) and in healthy volunteers. It is developed by Denali Therapeutics Inc. (DNLI). As of now, DNL343 is in Phase 1 clinical development and has not been approved by regulatory authorities.

Who makes DNL343?

DNL343 is being developed by Denali Therapeutics Inc., a biopharmaceutical company traded on the NASDAQ under the ticker DNLI. Denali is conducting clinical trials to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of DNL343 in healthy volunteers and in participants with ALS.

What phase is DNL343 in?

DNL343 is in Phase 1 clinical development. All completed trials for DNL343 are Phase 1 studies, including trials in healthy volunteers and in participants with Amyotrophic Lateral Sclerosis. DNL343 is investigational and has not received FDA approval.

What clinical trials is DNL343 in?

DNL343 has completed three Phase 1 trials: NCT04268784 in healthy volunteers in the Netherlands, NCT04581772 in healthy volunteers in New Zealand, and NCT05006352 in participants with ALS in the United States and Netherlands. A fourth trial, NCT06281158, studied the absorption and metabolism of a radiolabeled form of DNL343 in healthy males.

Is DNL343 the same as other names?

DNL343 is the primary name used in clinical trials and by the developer Denali Therapeutics. No alternative names have been reported for this investigational drug. It is a small molecule being studied for ALS and in healthy volunteer studies.