Amyotrophic Lateral SclerosisPhase 1NCT05006352
A Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis
A Phase 1 study testing DNL343 in people with Amyotrophic Lateral Sclerosis, run by Denali Therapeutics Inc. at 7 sites in 2 countries.
Trial summary
This is a Phase 1b, multicenter, randomized, placebo-controlled, double-blind study of 28 days, followed by an 18-month open-label extension, designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL343 in participants with amyotrophic lateral sclerosis (ALS) Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- DNL343
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 11 Aug 2021to 5 Jun 2024
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of sporadic or familial ALS
- ≤ 4 years since ALS symptom onset
- 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
- Vital capacity >50% predicted at screening
- Women must have been surgically sterilized, be postmenopausal, or for participants of childbearing potential, must not be pregnant, and both the participant and the male partner must use highly effective contraception
- Men, and sex partner if a woman of childbearing potential, must use highly effective contraception
Who cannot join
- Any history of unstable or poorly controlled psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders
- Positive serum pregnancy test or currently lactating or breastfeeding
- History of malignancy within 5 years
- History of clinically significant neurologic disorders other than ALS
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Emory University
Atlanta, Georgia, 30322
Atrium Health Neurosciences Institute
Charlotte, North Carolina, 28207
PPD Orlando
Orlando, Florida, 32806
University of California at San Diego
San Diego, California, 92093
California Pacific Medical Center
San Francisco, California, 94115
HonorHealth
Scottsdale, Arizona, 85251
Netherlands1 site
Centre for Human Drug Research (CHDR)
Leiden, South Holland, 2333
About this study
Official title: A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study, Followed by an Open-Label Extension, to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis
This is a Phase 1b, multicenter, randomized, placebo-controlled, double-blind study of 28 days, followed by an 18-month open-label extension, designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL343 in participants with amyotrophic lateral sclerosis (ALS)
Read the detailed description
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- DNL343, Placebo
- Keywords
- ALS
- 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.
DNL343Drug
Oral repeating dose
PlaceboDrug
Oral repeating dose
| Study group | Role | What they receive |
|---|---|---|
| DNL343 (High Dose) | Experimental | Not described Receives: Drug: DNL343 |
| DNL343 (Low Dose) | Experimental | Not described Receives: Drug: DNL343 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period
Measured: 28 Days
Secondary outcomes (5)
PK parameter: Maximum concentration (Cmax) of DNL343 in plasma
Measured: 19 months
PK parameter: Time to reach maximum concentration (tmax) of DNL343 in plasma
Measured: 19 months
PK parameter: Trough concentration (Ctrough) of DNL343 in plasma
Measured: 19 months
PK parameter: Area under the concentration-time curve from time zero to 24 hours (AUC24) of DNL343 in plasma
Measured: 19 months
Cerebrospinal fluid-to-plasma concentration ratio of DNL343 following multiple oral doses
Measured: 19 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2021
- Study start11 Aug 2021
- Primary completion15 Dec 2022
- Study completion5 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denali Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Linus Sun, MD, PhD, Study director, Denali Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05006352
- Sponsor's protocol ID
- DNLI-F-0003
- Other IDs
- 2021-001766-37
- Status last verified
- Sep 2024
- First submitted
- 7 Aug 2021
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study, Followed by an Open-Label Extension, to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT05006352
- Acronym / sponsor ID
- DNLI-F-0003
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Denali Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Aug 2021 (actual)
- Primary completion
- 15 Dec 2022 (actual)
- Study completion
- 5 Jun 2024 (actual)
- First posted
- 16 Aug 2021 (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.
This is a Phase 1b, multicenter, randomized, placebo-controlled, double-blind study of 28 days, followed by an 18-month open-label extension, designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL343 in participants with amyotrophic lateral sclerosis (ALS)
Detailed description
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DNL343 (High Dose) | Experimental | Drug: DNL343 |
| DNL343 (Low Dose) | Experimental | Drug: DNL343 |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of sporadic or familial ALS
- ≤ 4 years since ALS symptom onset
- 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
- Vital capacity >50% predicted at screening
Key exclusion criteria (4 listed)
- Any history of unstable or poorly controlled psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders
- Positive serum pregnancy test or currently lactating or breastfeeding
- History of malignancy within 5 years
- History of clinically significant neurologic disorders other than ALS
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 |
|---|---|---|
| DNL343Oral repeating dose | Drug | DNL343 (High Dose), DNL343 (Low Dose) |
| PlaceboOral repeating dose | Drug | Placebo |
Primary outcome
Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period
Time frame: 28 Days
5 secondary outcomes
PK parameter: Maximum concentration (Cmax) of DNL343 in plasma
Time frame: 19 months
PK parameter: Time to reach maximum concentration (tmax) of DNL343 in plasma
Time frame: 19 months
PK parameter: Trough concentration (Ctrough) of DNL343 in plasma
Time frame: 19 months
PK parameter: Area under the concentration-time curve from time zero to 24 hours (AUC24) of DNL343 in plasma
Time frame: 19 months
Cerebrospinal fluid-to-plasma concentration ratio of DNL343 following multiple oral doses
Time frame: 19 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
Related trials for Amyotrophic Lateral Sclerosis
RecruitingPhase 1/2
Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS
Amyotrophic Lateral Sclerosis
Not yet recruiting
A Study on the Addition of Alsum30 for the Treatment of Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis (ALS), Bacillus Coagulans
Active, not recruiting
Functional Outcomes and Control Using Synchron BCI - Australia
Neurologic Disorder, Neurologic Diseases
Not yet recruitingPhase 1
Safety, Tolerability, and Pharmacodynamic Exploration of Orelabrutinib in Patients With Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS)
Recruiting
Clinical Outcome Assessment for AT & BCI
Spinal Cord Injury, ALS (Amyotrophic Lateral Sclerosis)
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.
Linus Sun, MD, PhD study director
Denali Therapeutics Inc.
7 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 DNL343 in people with Amyotrophic Lateral Sclerosis, run by Denali Therapeutics Inc. at 7 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 7 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: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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. Some participants in this study may receive a placebo. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period (time frame: 28 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Sep 2024.