Study to Evaluate DNL747 in Subjects With Alzheimer's Disease

Denali Therapeutics

Status and phase: Completed; Phase 1

Conditions: Alzheimer Disease

Treatments: Drug: Placebo; Drug: DNL747

Study type: Interventional

Funder types: Industry

Identifiers

NCT03757325

DNLI-D-0002

Details and patient eligibility

About

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

Full 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)

Enrollment: 16 patients

Sex: All

Ages: 55 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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16 participants in 2 patient groups

DNL747 First, Placebo Second

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: DNL747

Placebo First, DNL747 Second

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: DNL747