Alzheimer's Disease, Healthy Participants
Conditions
Brief summary
This is a Phase 1/1b, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of DNL921 in healthy participants and participants with Alzheimer's disease (AD). The principal aim of this study is to obtain safety and tolerability data. This information, together with PK and PD data, will inform dose selection and design of future studies.
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.).
Interventions
DRUGDNL921
Single or multiple doses
DRUGPlacebo
Single or multiple doses matched to experimental treatment
Sponsors
Denali Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria (Healthy Participants): * Are male or female of non-childbearing potential and are aged 18 through 60 years at the time of screening * Have a BMI of 18 through 32 kg/m2 and a body weight of at least 50 kg * For female participants: Are of non-childbearing potential * For male participants: Are surgically sterile by bilateral orchidectomy, or are abstinent, or agree to use two acceptable forms of contraception Key
Exclusion criteria
(Healthy Participants): * Have any history of clinically significant neurological, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematological, immunological, or allergic disease, or other major disorders * Have a positive serum pregnancy test or are currently lactating or breastfeeding * Have been hospitalized during the 4 weeks prior to screening Key Inclusion Criteria (Participants with AD): * Are male or female of non-childbearing potential and aged 50 to 75 years at the time of screening * Have a BMI between 18 and 32 kg/m2 and a body weight of at least 45 kg * Have a diagnosis of probable mild to moderate AD dementia based on NIA AA 2011 criteria, including amnestic or nonamnestic presentation at screening or prodromal AD (consistent with the NIA-AA diagnostic criteria and guidelines for mild cognitive impairment due to AD) * Have supportive evidence of AD pathology by the following: * Plasma ptau217/Abeta42 positive * Positive amyloid PET scan * For female participants: Are of non-childbearing potential * For male participants: Are surgically sterile by bilateral orchidectomy, or are abstinent, or agree to use two acceptable forms of contraception Key
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Incidence and severity of treatment-emergent averse events (TEAEs) | 46 days |
| Parts B and C: Incidence and severity of TEAEs in participants with AD | 242 days |
Secondary
| Measure | Time frame |
|---|---|
| PK Parameter: Maximum concentration (Cmax) of DNL921 in serum | Up to 242 Days |
| PK Parameter: Time to reach maximum concentration (tmax) of DNL921 in serum | Up to 242 Days |
| PK Parameter: Area under the concentration-time curve (AUC) from time zero to time of last measurable concentration (AUClast) of DNL921 in serum | Up to 242 Days |
| Part A: PK Parameter: AUC from time zero to infinity of DNL921 in serum | 46 Days |
| PK Parameter: Elimination half-life (t1/2) of DNL921 in serum | Up to 242 Days |
| Parts B and C: PK Parameter: Time to reach minimum concentration (Cmin) of DNL921 in serum | 242 Days |
| Parts B and C: PK Parameter: AUC during a dosing interval (AUCtau) of DNL921 in serum | 242 Days |
| Parts B and C: PK Parameter: Accumulation ratio of DNL921 in serum | 242 Days |
| Parts B and C: Change from baseline in brain amyloid load at Weeks 12 and 28 as measured by amyloid PET scan | 28 Weeks |
| Parts B and C: Amyloid clearance at Weeks 12 and 28 as measured by amyloid PET scan | 28 Weeks |
Countries
United Kingdom
Contacts
CONTACTClinical Trials at Denali Therapeutics
STUDY_DIRECTORMedical Monitor
Denali Therapeutics Inc.
Outcome results
None listed