Alzheimer DiseasePhase 1NCT03757325
Study to Evaluate DNL747 in Subjects With Alzheimer's Disease
A Phase 1 study testing DNL747 in people with Alzheimer Disease, run by Denali Therapeutics Inc. at 5 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 Alzheimer's disease when administered for 29 days in a cross-over design Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- DNL747
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 13 Feb 2019to 5 Dec 2019
- 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 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women of non-childbearing potential and men, aged 55-85 years
- AD diagnosis based on the 2011 National Institute on Aging-Alzheimer's Association Guidelines
- Supportive evidence for diagnosis of AD based upon positive CSF Aβ42 test, or documented history of positive amyloid-specific PET scan
- Screening MMSE score of 16-26 points
- Screening CDR Global Score of 0.5-1.0
- Availability of a person ("caregiver") who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits that require input for scale completion, assists the participant with compliance for at-home study treatment administration, and signs the necessary consent form (note: the caregiver is not required to stay in the unit)
- Approved AD treatments (acetylcholinesterase inhibitors ± memantine) and other prescription medications must be stable for ≥1 month prior to screening and anticipated to be stable over the duration of the study
Who cannot join
- Clinical history within 2 years of the screening visit or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
- Magnetic resonance imaging (MRI) at screening (or within 1 year of screening visit) consistent with any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Clinical Site(s)
Dallas, Texas, 75231
Clinical Site(s)
Miami, Florida, 33143
Clinical Site(s)
Orlando, Florida, 32806
Clinical Site(s)
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 Alzheimer's Disease
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL747 in subjects with Alzheimer's disease when administered for 29 days in a cross-over design
Read the detailed description
This is a Phase 1b randomized, placebo-controlled, double-blind, crossover study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL747 in subjects with Alzheimer's disease (AD)
- Conditions
- Alzheimer Disease
- Being tested
- DNL747, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNL747Drug
DNL747
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| DNL747 First, Placebo Second | Experimental | Subjects will receive DNL747 for 29 days for the first period and then will switch to placebo for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods. Receives: Drug: DNL747; Drug: Placebo |
| Placebo First, DNL747 Second | Experimental | Subjects will receive placebo for 29 days for the first period and then will switch to DNL747 for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods. Receives: Drug: DNL747; Drug: Placebo |
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 start13 Feb 2019
- Primary completion5 Dec 2019
- Study completion5 Dec 2019
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 Alzheimer DiseaseStudies 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
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denali Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03757325
- Sponsor's protocol ID
- DNLI-D-0002
- Status last verified
- Feb 2020
- First submitted
- 27 Nov 2018
- Last updated
- 26 Feb 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 26 Feb 2020. 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 Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03757325
- Acronym / sponsor ID
- DNLI-D-0002
- Conditions
- Alzheimer Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Denali Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Feb 2019 (actual)
- Primary completion
- 5 Dec 2019 (actual)
- Study completion
- 5 Dec 2019 (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 Alzheimer's disease when administered for 29 days in a cross-over design
Detailed description
This is a Phase 1b randomized, placebo-controlled, double-blind, crossover study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL747 in subjects with Alzheimer's disease (AD)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DNL747 First, Placebo Second | Experimental | Drug: DNL747, Drug: PlaceboSubjects will receive DNL747 for 29 days for the first period and then will switch to placebo for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods. |
| Placebo First, DNL747 Second | Experimental | Drug: DNL747, Drug: PlaceboSubjects will receive placebo for 29 days for the first period and then will switch to DNL747 for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Women of non-childbearing potential and men, aged 55-85 years
- AD diagnosis based on the 2011 National Institute on Aging-Alzheimer's Association Guidelines
- Supportive evidence for diagnosis of AD based upon positive CSF Aβ42 test, or documented history of positive amyloid-specific PET scan
- Screening MMSE score of 16-26 points
- Screening CDR Global Score of 0.5-1.0
Key exclusion criteria (2 listed)
- Clinical history within 2 years of the screening visit or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
- Magnetic resonance imaging (MRI) at screening (or within 1 year of screening visit) consistent with any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
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 |
|---|---|---|
| DNL747DNL747 | Drug | DNL747 First, Placebo Second, Placebo First, DNL747 Second |
| PlaceboPlacebo | 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 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 26 Feb 2020.
- 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.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 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 Alzheimer Disease, run by Denali Therapeutics Inc. at 5 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 2 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 26 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 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?
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 NCT03757325, 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 26 Feb 2020.