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Study to Evaluate DNL201 in Subjects With Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT03710707
Recruitment Status : Recruiting
First Posted : October 18, 2018
Last Update Posted : November 1, 2018
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 DNL201 in subjects with Parkinson's disease.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: DNL201 low dose Drug: DNL201 high dose Drug: Placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL201 in Subjects With Parkinson's Disease
Estimated Study Start Date : October 2018
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: DNL201 low dose
DNL201 low dose will be orally administered.
Drug: DNL201 low dose
DNL201 low dose

Experimental: DNL201 high dose
DNL201 high dose will be orally administered.
Drug: DNL201 high dose
DNL201 high dose

Placebo Comparator: Placebo
Placebo will be orally administered.
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Randomization to Day 42 ]
  2. Number of Subjects with laboratory test abnormalities [ Time Frame: Randomization to Day 42 ]
  3. Number of Subjects with vital sign abnormalities [ Time Frame: Randomization to Day 42 ]
  4. Number of Subjects with electrocardiogram (ECG) abnormalities [ Time Frame: Randomization to Day 42 ]
  5. Number of Subjects with clinically significant neurological examination abnormalities [ Time Frame: Randomization to Day 42 ]

Secondary Outcome Measures :
  1. Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL201 [ Time Frame: Randomization to Day 28 ]
  2. Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL201 [ Time Frame: Randomization to Day 28 ]
  3. Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL201 [ Time Frame: Randomization to Day 28 ]
  4. Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL201 [ Time Frame: Randomization to Day 28 ]
  5. Pharmacokinetic measure of CSF concentrations of DNL201 [ Time Frame: Randomization to Day 28 ]
  6. Pharmacodynamic measure of pS935 in whole blood and/or PBMCs [ Time Frame: Randomization to Day 28 ]
  7. Pharmacodynamic measure of pRab10 in PBMCs [ Time Frame: Randomization to Day 28 ]


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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body mass index (BMI) between 18 and 35.0 kg/m2, inclusive
  • Clinical diagnosis of Parkinson's disease meeting UK Brain Bank criteria and H&Y Stage I, II, or III.
  • sPD subgroup without a LRRK2 mutation; PD LRRK2 subgroup with LRRK2 mutation
  • Screening dopamine transporter (DAT) SPECT scan with a DAT deficit consistent with Parkinson's disease
  • Able to hold Parkinson's disease medications 8 hours (overnight) prior to specific study assessments

Exclusion Criteria:

  • Any history of clinically significant asthma, chronic obstructive pulmonary disease, or emphysema within 5 years of screening, or other clinically significant pulmonary disease within 6 months of screening
  • Abnormal Vitals including Respiratory Rate, Body Temperature, and Blood Pressure
  • Pulmonary Function Tests (PFTs) (FVC <60% predicted, FEV1 <50% predicted, FEV1:FVC ratio <0.6, DLCO <70% predicted)
  • Clinically significant neurologic disorder other than Parkinson's disease, including history of stroke, cognitive impairment, seizure within 5 years of screening, or head trauma with loss of consciousness within 6 months of screening
  • Montreal Cognitive Assessment (MoCA) score of <24 at screening

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): NCT03710707


Contacts
Contact: Project Assistant 919-456-5345 DNLI-B-0002.SM@ppdi.com

Locations
United States, California
CNS Network Recruiting
Long Beach, California, United States, 90806
Contact: Recruitment Coordinator    562-304-1759    EdwinGhil@cnstrial.com   
United States, Colorado
University of Denver, Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Bioclinica Research Not yet recruiting
Orlando, Florida, United States, 32806
Contact: Recruitment Coordinator    407-210-9835    leslie.McClelland@bioclinica.com   
United States, Michigan
Henry Ford Hospital Not yet recruiting
Farmington Hills, Michigan, United States, 480202
QUEST Research Institute Not yet recruiting
Farmington Hills, Michigan, United States, 48334
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Denali Therapeutics Inc.

Responsible Party: Denali Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03710707     History of Changes
Other Study ID Numbers: DNLI-B-0002
First Posted: October 18, 2018    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018

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

Keywords provided by Denali Therapeutics Inc.:
LRRK2
Parkinson's Disease
Movement Disorders

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases