Study to Evaluate DNL747 in Subjects With Alzheimer's Disease

• Sponsor: Denali Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03757325
• Collaborator: (none)
• Enrollment: 16
• Locations: 5
• Arms: 2
• Actual Duration (Months): 9.7
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: DNL747; Drug: Placebo	Phase 1

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

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 13, 2019
• Actual Primary Completion Date: Dec 5, 2019
• Actual Study Completion Date: Dec 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DNL747 First, Placebo Second 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.	Drug: DNL747; DNL747; Drug: Placebo; Placebo
Experimental: Placebo First, DNL747 Second 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.	Drug: DNL747; DNL747; Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Randomization - Day 86]

2. Number of Subjects with clinically significant neurological examination abnormalities [Randomization - Day 86]

3. Number of Subjects with laboratory test abnormalities [Randomization - Day 86]

Secondary Outcome Measures

1. Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747 [Randomization - Day 86]

2. Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747 [Randomization - Day 86]

3. Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747 [Randomization - Day 86]

4. Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747 [Randomization - Day 86]

5. Pharmacokinetic measure of CSF concentrations of DNL747 [Randomization - Day 86]

6. Pharmacodynamic measure of pS166 in PBMCs [Randomization - Day 86]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Site(s)	Miami	Florida	United States	33143
2	Clinical Site(s)	Orlando	Florida	United States	32806
3	Clinical Site(s)	Dallas	Texas	United States	75231
4	Clinical Site(s)	Salt Lake City	Utah	United States	84124
5	Clinical Site(s)	Groningen		Netherlands	9713

Sponsors and Collaborators

• Denali Therapeutics Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Denali Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03757325
• Other Study ID Numbers: DNLI-D-0002
• First Posted: Nov 28, 2018
• Last Update Posted: Feb 26, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

No Results Posted as of Feb 26, 2020