Study to Evaluate DNL151 in Subjects With Parkinson's Disease

Phase 1

Completed

• Conditions: Parkinson's Disease
• Interventions: Drug: DNL151; Drug: Placebo

• Registration Number: NCT04056689
• Lead Sponsor: Biogen

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL151 in subjects with Parkinson's disease.

Detailed Description

This study was previously posted by Denali Therapeutics. In July, 2022, sponsorship of the trial was transferred to Biogen.

Study Timeline

• Study Start: 2019-07-23
• Study First Submitted: 2019-08-12
• Study First Submitted QC: 2019-08-12
• Study First Posted: 2019-08-14
• Primary Completion: 2020-12-02
• Study Completion: 2020-12-02
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-14
• Last Update Posted: 2023-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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.
• Able to hold Parkinson's disease medications 8 hours (overnight) prior to specific study assessments

Key

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, Blood Pressure, and Pulse Rate
• 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 within 12 months of screening, 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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
DNL151 Low Dose	DNL151	-
DNL151 Mid Dose	DNL151	-
DNL151 High Dose	DNL151	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Randomization to Day 42
Number of Subjects with vital sign abnormalities	Randomization to Day 42
Number of Subjects with clinically significant neurological examination abnormalities	Randomization to Day 42
Number of Subjects with laboratory test abnormalities	Randomization to Day 42
Number of Subjects with electrocardiogram (ECG) abnormalities	Randomization to Day 42

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL151	Randomization to Day 28
Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL151	Randomization to Day 28
Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL151	Randomization to Day 28
Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL151	Randomization to Day 28
Pharmacokinetic measure of CSF concentrations of DNL151	Randomization to Day 28
Pharmacodynamic measure of pS935 in whole blood	Randomization to Day 28
Pharmacodynamic measure of pRab10 in PBMCs	Randomization to Day 28

Trial Locations

Locations (8)

QPS; 🇳🇱 Leeuwarden, Netherlands

Simbec-Orion Clinical Pharmacology; 🇬🇧 Merthyr Tydfil, United Kingdom

UZ Leuven; 🇧🇪 Leuven, Belgium

Centre for Human Drug Research; 🇳🇱 Leiden, South Holland, Netherlands

MAC Clinical Research; 🇬🇧 Manchester, United Kingdom

PPD Clinical Research Unit; 🇺🇸 Orlando, Florida, United States

Quest Research Institute; 🇺🇸 Farmington Hills, Michigan, United States

Royal Liverpool University Hospital; 🇬🇧 Liverpool, United Kingdom