Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis

September 17, 2025 updated by: Sanofi

A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL747 in Subjects With Amyotrophic Lateral Sclerosis

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL747 in subjects with Amyotrophic Lateral Sclerosis in a cross-over design

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • South Holland
      • Leiden, South Holland, Netherlands, 2333
        • CHDR
  • United States
    • Florida
      • Orlando, Florida, United States, 32806
        • Bioclinica
    • Utah
      • Salt Lake City, Utah, United States, 84124
        • PRA Health Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria (Double-Blind Part):

  • Women of non-childbearing potential and men, aged 21-80 years
  • Willingness and ability to complete all aspects of the study; participant should be capable of completing assessments either alone or with help of a caregiver
  • Diagnosis of laboratory-supported probable, probable, or definite (sporadic or familial) ALS according to the El Escorial World Federation of Neurology revised research diagnostic criteria
  • Less than 3 years since symptom onset
  • Forced vital capacity (FVC) >50% predicted measured within 30 days of screening
  • If subject is taking approved ALS treatments (riluzole and/or edaravone), doses must be stable for ≥2 months prior to screening and subject is expected to stay on a stable regimen throughout the study

Key Exclusion Criteria (Double-Blind Part):

  • History of a clinically significant non-ALS neurologic disorder (other than frontal temporal lobe dementia), including, but not limited to, muscular dystrophy, spinal stenosis, peripheral neuropathy, inherited neuropathies, AD, Parkinson's disease, Lewy body dementia, vascular dementia, Huntington's disease, epilepsy, stroke, multiple sclerosis, brain tumor, or brain infection or abscess
  • Unstable or poorly controlled comorbid disease process of any organ system currently requiring active treatment or likely to require treatment adjustment during the study

Key Inclusion Criteria (Open-Label Extension):

  • Successful completion of both periods of the the double-blind, crossover part of the study
  • Continued diagnosis of laboratory-supported probable, probable, or definite (sporadic or familial) ALS according to the El Escorial World Federation of Neurology revised research diagnostic criteria

Key Exclusion Criteria (Open-Label Extension):

  • Presence of laboratory abnormalities, physical examination findings, or AEs determined to be clinically significant by the investigator from the double-blind part of the study that have not resolved by the final follow-up visit as part of the double-blind study period
  • New diagnosis of clinically significant neurological disorder (other than frontal temporal lobe dementia)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: DNL747 First, Placebo Second
Drug: DNL747
Repeating oral dose
Drug: Placebo
Repeating oral dose
Experimental: Placebo First, DNL747 Second
Drug: DNL747
Repeating oral dose
Drug: Placebo
Repeating oral dose
Experimental: Open-Label Extension
Conducted in the Netherlands only.
Drug: DNL747
Repeating oral dose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Randomization - Day 86
Randomization - Day 86
Number of Subjects with clinically significant neurological examination abnormalities
Time Frame: Randomization - Day 86
Randomization - Day 86
Number of Subjects with laboratory test abnormalities
Time Frame: Randomization - Day 86
Randomization - Day 86

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747
Time Frame: Randomization - Day 86
Randomization - Day 86
Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747
Time Frame: Randomization - Day 86
Randomization - Day 86
Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747
Time Frame: Randomization - Day 86
Randomization - Day 86
Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747
Time Frame: Randomization - Day 86
Randomization - Day 86
Pharmacokinetic measure of CSF concentrations of DNL747
Time Frame: Randomization - Day 86
Randomization - Day 86
Pharmacodynamic measure of pS166 in PBMCs
Time Frame: Randomization - Day 86
Randomization - Day 86

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sanofi

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Denali Therapeutics Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 14, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 18, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 18, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 27, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 27, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 28, 2018

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TDR16536
  • DNLI-D-0003 (Other Identifier: Denali Therapeutics Inc.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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