29 Participants Needed

DNL343 for Amyotrophic Lateral Sclerosis

Recruiting at 6 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Denali Therapeutics Inc.
Must be taking: Riluzole, Edaravone

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DNL343 for people with amyotrophic lateral sclerosis (ALS), a disease affecting nerve cells in the brain and spinal cord. The trial aims to determine if DNL343 is safe and how it behaves in the body. Participants will receive either a low dose, a high dose, or a placebo (a non-active substance) to compare effects. People with ALS who have had symptoms for 4 years or less, are on stable ALS medications, and can swallow pills might be a good fit for this trial. As a Phase 1 trial, this research focuses on understanding how DNL343 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Is there any evidence suggesting that DNL343 is likely to be safe for humans?

Research shows that DNL343 is under study to determine its safety for people with amyotrophic lateral sclerosis (ALS). In earlier studies, researchers tested DNL343 on both healthy individuals and those with ALS. The results indicated that the treatment was generally well-tolerated. Some side effects occurred, but they were not serious and resembled those seen with other treatments.

This trial is in the early stages, so researchers are primarily focused on assessing the treatment's safety. While detailed information about all possible side effects is not yet available, these early results provide insight into the safety of DNL343.12345

Why do researchers think this study treatment might be promising?

Researchers are excited about DNL343 for treating Amyotrophic Lateral Sclerosis (ALS) because it works differently from existing options like Riluzole and Edaravone. Most ALS treatments focus on slowing disease progression by targeting neurotransmitter pathways or reducing oxidative stress. However, DNL343 is unique because it targets protein synthesis pathways, potentially addressing the underlying causes of neuronal damage. This novel approach could offer a new way to slow or alter the disease course, providing hope for better outcomes in ALS management.

What evidence suggests that DNL343 might be an effective treatment for ALS?

Research suggests that DNL343, which participants in this trial may receive, might help treat amyotrophic lateral sclerosis (ALS). Early studies show that DNL343 can reach the brain and spinal fluid, the areas affected by ALS. It works by blocking a cellular process called the integrated stress response (ISR), which contributes to ALS development. Although it did not achieve the main goals of improving function and survival in some trials, it was safe and well-tolerated. DNL343 has also shown promise in possibly lowering a key blood marker linked to ALS. Overall, there is hope that DNL343 could help manage ALS symptoms in the future.24567

Who Is on the Research Team?

LS

Linus Sun, MD, PhD

Principal Investigator

Denali Therapeutics Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

Your lung function is good, and you can breathe well.
Stable doses of approved ALS treatments (riluzole and/or edaravone) for at least 2 months prior to screening
Participants must be able to swallow the study intervention
See 4 more

Exclusion Criteria

Positive serum pregnancy test or currently lactating or breastfeeding
You have a history of serious health problems that are not well managed or under control.
You have been diagnosed with cancer in the past 5 years.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either DNL343 or placebo for 28 days to evaluate safety, pharmacokinetics, and pharmacodynamics

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment with DNL343 for 18 months

18 months

What Are the Treatments Tested in This Trial?

Interventions

  • DNL343
  • Placebo
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Placebo Group
Group I: DNL343 (Low Dose)Experimental Treatment1 Intervention
Group II: DNL343 (High Dose)Experimental Treatment1 Intervention
Group III: PlaceboPlacebo Group1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Denali Therapeutics Inc.

Lead Sponsor

Trials
24
Recruited
1,900+

Citations

Results from Regimen G in the Healey Platform TrialDNL343 in Amyotrophic Lateral Sclerosis: Results from Regimen G in the Healey Platform Trial. Danna Jennings, MD. Denali Therapeutics. Page 2. Denali ...
DNL343 Falls Short of Primary End Point in Phase 2/3 ...DNL343 did not meet primary endpoints for function and survival in ALS patients but was safe and well-tolerated. · Further analyses, including ...
Investigational eIF2B activator DNL343 modulates the ...DNL343 demonstrated a half-life supporting once-daily dosing and showed extensive CSF distribution. DNL343 was generally well tolerated and ...
HEALEY ALS Platform Trial - Regimen G DNL343Regimen G will evaluate the safety and efficacy of a single study drug, DNL343, in participants with ALS. ... The Amyotrophic Lateral Sclerosis Functional Rating ...
Denali Therapeutics: Learning from the DNL343 Trial in ALSInitial studies showed encouraging signs; DNL343 reached the brain and spinal fluid, inhibited the ISR in patient cells, and reduced a key blood ...
NCT05006352 | A Study to Determine the Safety, ...Also called a data safety ... A Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis.
Amyotrophic Lateral Sclerosis (ALS) Clinical Program - DenaliDNL343 is being studied to determine if it may slow or stop the progression of neurodegeneration in ALS. Denali is studying the effects and safety of DNL343 ...
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