Amyotrophic Lateral SclerosisPhase 1NCT03757351
Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis
A Phase 1 study testing DNL747 in people with Amyotrophic Lateral Sclerosis, run by Sanofi at 3 sites in 2 countries.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- DNL747
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 14 Dec 2018to 18 Jun 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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
Who cannot join
- 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
- 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)
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Bioclinica
Orlando, Florida, 32806
PRA Health Sciences
Salt Lake City, Utah, 84124
About this study
Official title: 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
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- DNL747, Placebo
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNL747Drug
Repeating oral dose
PlaceboDrug
Repeating oral dose
| Study group | Role | What they receive |
|---|---|---|
| DNL747 First, Placebo Second | Experimental | Not described Receives: Drug: DNL747; Drug: Placebo |
| Placebo First, DNL747 Second | Experimental | Not described Receives: Drug: DNL747; Drug: Placebo |
| Open-Label Extension | Experimental | Conducted in the Netherlands only. Receives: Drug: DNL747 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Randomization - Day 86
Number of Subjects with clinically significant neurological examination abnormalities
Measured: Randomization - Day 86
Number of Subjects with laboratory test abnormalities
Measured: Randomization - Day 86
Secondary outcomes (6)
Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747
Measured: Randomization - Day 86
Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747
Measured: Randomization - Day 86
Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747
Measured: Randomization - Day 86
Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747
Measured: Randomization - Day 86
Pharmacokinetic measure of CSF concentrations of DNL747
Measured: Randomization - Day 86
Pharmacodynamic measure of pS166 in PBMCs
Measured: Randomization - Day 86
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2018
- Study start14 Dec 2018
- Primary completion18 Jun 2020
- Study completion18 Jun 2020
Why it stopped: Due to change in Sanofi's development strategy for DNL747/SAR443060 - not due to any safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Denali Therapeutics Inc.
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03757351
- Sponsor's protocol ID
- TDR16536
- Other IDs
- DNLI-D-0003
- Status last verified
- Sep 2025
- First submitted
- 27 Nov 2018
- Last updated
- 22 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Vissers MFJM, Heuberger JAAC, Groeneveld GJ, Oude Nijhuis J, De Deyn PP, Hadi S, Harris J, Tsai RM, Cruz-Herranz A, Huang F, Tong V, Erickson R, Zhu Y, Scearce-Levie K, Hsiao-Nakamoto J, Tang X, Chang M, Fox BM, Estrada AA, Pomponio RJ, Alonso-Alonso M, Zilberstein M, Atassi N, Troyer MD, Ho C. Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients. Clin Transl Sci. 2022 Aug;15(8):2010-2023. doi: 10.1111/cts.13317. Epub 2022 Jun 1.
PubMed 35649245
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03757351
- Acronym / sponsor ID
- TDR16536
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to change in Sanofi's development strategy for DNL747/SAR443060 - not due to any safety concerns
- Enrolment
- 15 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Denali Therapeutics Inc.
- Study start
- 14 Dec 2018 (actual)
- Primary completion
- 18 Jun 2020 (actual)
- Study completion
- 18 Jun 2020 (actual)
- First posted
- 28 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DNL747 First, Placebo Second | Experimental | Drug: DNL747, Drug: Placebo |
| Placebo First, DNL747 Second | Experimental | Drug: DNL747, Drug: Placebo |
| Open-Label Extension | Experimental | Drug: DNL747Conducted in the Netherlands only. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (4 listed)
- 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
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DNL747Repeating oral dose | Drug | DNL747 First, Placebo Second, Open-Label Extension, Placebo First, DNL747 Second |
| PlaceboRepeating oral dose | Drug | DNL747 First, Placebo Second, Placebo First, DNL747 Second |
Primary outcome
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Randomization - Day 86
Number of Subjects with clinically significant neurological examination abnormalities
Time frame: Randomization - Day 86
Number of Subjects with laboratory test abnormalities
Time frame: Randomization - Day 86
6 secondary outcomes
Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747
Time frame: Randomization - Day 86
Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747
Time frame: Randomization - Day 86
Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747
Time frame: Randomization - Day 86
Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747
Time frame: Randomization - Day 86
Pharmacokinetic measure of CSF concentrations of DNL747
Time frame: Randomization - Day 86
Pharmacodynamic measure of pS166 in PBMCs
Time frame: Randomization - Day 86
Results and safety
The study was stopped early (reason given: Due to change in Sanofi's development strategy for DNL747/SAR443060 - not due to any safety concerns). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2025.
- Derived from this study: PubMed 35649245Vissers MFJM, Heuberger JAAC, Groeneveld GJ, Oude Nijhuis J, De Deyn PP, Hadi S, Harris J, Tsai RM, Cruz-Herranz A, Huang F, Tong V, Erickson R, Zhu Y, Scearce-Levie K, Hsiao-Nakamoto J, Tang X, Chang M, Fox BM, Estrada AA, Pomponio RJ, Alonso-Alonso M, Zilberstein M, Atassi N, Troyer MD, Ho C. Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients. Clin Transl Sci. 2022 Aug;15(8):2010-2023. doi: 10.1111/cts.13317. Epub 2022 Jun 1.
- TDR16536 Plain Language Results SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DNL747 in people with Amyotrophic Lateral Sclerosis, run by Sanofi at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to change in Sanofi's development strategy for DNL747/SAR443060 - not due to any safety concerns). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Randomization - Day 86). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03757351, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2025; AzTrials last refreshed its copy on 1 Nov 2026.