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Study to Evaluate DNL747 in Subjects With Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT03757325
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : April 25, 2019
Sponsor:
Information provided by (Responsible Party):
Denali Therapeutics Inc.

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)

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 13, 2019
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Randomization - Day 86 ]
  2. Number of Subjects with clinically significant neurological examination abnormalities [ Time Frame: Randomization - Day 86 ]
  3. Number of Subjects with laboratory test abnormalities [ Time Frame: Randomization - Day 86 ]

Secondary Outcome Measures :
  1. Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747 [ Time Frame: Randomization - Day 86 ]
  2. Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747 [ Time Frame: Randomization - Day 86 ]
  3. Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747 [ Time Frame: Randomization - Day 86 ]
  4. Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747 [ Time Frame: Randomization - Day 86 ]
  5. Pharmacokinetic measure of CSF concentrations of DNL747 [ Time Frame: Randomization - Day 86 ]
  6. Pharmacodynamic measure of pS166 in PBMCs [ Time Frame: Randomization - Day 86 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 18−26 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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03757325


Contacts
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Contact: Melissa Leedom 1 913 624 4970 Melissa.Leedom@iqvia.com

Locations
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United States, Florida
QPS Miami Research Associates Recruiting
Miami, Florida, United States, 33143
Contact: Kaylee Johnson    302-509-8766    kaylee.johnson@qps.com   
Bioclinica Research Recruiting
Orlando, Florida, United States, 32806
Contact: Matthew Bubalo    407-841-0502    Matthew.Bubalo@bioclinica.com   
United States, Texas
Diana Kerwin Research Center Recruiting
Dallas, Texas, United States, 75231
Contact: Sarah Sutton    214-345-1239    SarahSutton@KerwinResearchCenter.com   
United States, Utah
PRA Health Sciences Recruiting
Salt Lake City, Utah, United States, 84124
Contact: Megan Cuello    801-904-4646    CuelloMegan@prahs.com   
Netherlands
QPS Recruiting
Groningen, Netherlands, 9713
Sponsors and Collaborators
Denali Therapeutics Inc.

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Responsible Party: Denali Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03757325     History of Changes
Other Study ID Numbers: DNLI-D-0002
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders