Clinical trial NCT03272165: Single Ascending Dose Study of MEDI1341 in Healthy Volunteers
Official title: A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of MEDI1341 in Healthy Male and Female Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Keywords: Healthy Volunteers
Safety
Tolerability
Pharmacokinetics
Pharmacodynamics
Immunogenicity
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Covance
name: MMS Holdings, Inc
name: Catalent
name: Takeda
First posted: 2017-09-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are randomized to one of two groups within a cohort of 8 participants (N=6 MEDI1341; N=2 placebo)
Primary purpose: TREATMENT

Brief summary: This is a study of single ascending intravenous doses of MEDI1341 or placebo in up to 48 healthy volunteers, aged 18 to 65 years. The study will include up to 6 planned cohorts; each cohort will comprise 8 participants.

Each participant will receive a single 60 minute intravenous infusion of MEDI1341 or placebo and will undergo scheduled assessments over a period of 13 weeks.

The main aim of the study is to assess the safety and tolerability of single doses of MEDI1341 in healthy volunteers.

Detailed description: This is a randomized, double-blind, placebo-controlled study of single ascending intravenous doses of MEDI1341 in male and nonfertile female healthy volunteers, aged 18 to 65 years.

The study will include up to 6 planned cohorts; each cohort will comprise 8 participants. Within each cohort, 6 participants will be randomized to receive MEDI1341 and 2 will be randomized to receive placebo. A Safety Review Committee will review data from each cohort before progression to the next higher dose cohort occurs. On Day 1, each randomized participant will receive a single 60 minute intravenous infusion of MEDI1341 or placebo and will undergo scheduled safety, pharmacokinetic, pharmacodynamic, and immunogenicity assessments. Additional study assessments will occur on Days 2, 4, 8, 15, 22, 29, 43, 57, and 92.

Eligibility criteria: Inclusion Criteria:

* Participants must be healthy, with no clinically significant abnormality identified on the medical or laboratory evaluation at screening
* Participants must weigh ≥50 kg and must have a body mass index between 18 and 32 kg/m\^2, inclusive
* Participants must have a 12-lead electrocardiogram recorded at screening that is normal for the appropriate age group and shows no abnormalities that will compromise safety in this study
* Participants must have no clinically significant findings on the clinical neurological examinations at screening and at baseline or on the ophthalmic examination at screening.

Exclusion Criteria:

* Nicotine use within 6 months before screening
* Considered to be at a high risk of developing a stroke
* Significant medical history of dizziness, blackouts, fainting, or vaso-vagal attacks
* History of any significant ophthalmic disorder, including congenital, genetic or acquired conditions affecting the retina or choroid
* History of severe allergy or history of hypersensitivity to immunizations or immunoglobulins
* History of any significant psychiatric disorder
* History of alcohol abuse
* History of cancer within 5 years of screening
* History of drug abuse
* Any contraindication to Lumbar Puncture
* Any clinically significant abnormality in ECG rhythm, conduction or morphology
* Positive serologic findings at screening for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies
* Use of prescription or non-prescription drugs
* For female participants, a positive serum or urine pregnancy test result at screening

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through 92 days after a single dose of study drug
measure: Number of Participants With Abnormal Vital Signs, Physical and Neurological Examinations, and Body Weight Measurements Reported as TEAEs
timeFrame: Day 1 through 92 days after a single dose of study drug
measure: Change from Baseline in 12-Lead Electrocardiogram (ECG) Data in Paper and Digital Recordings (PR Interval, QRS Duration, QT Interval, QTcF Interval, and RR Interval)
timeFrame: 12-lead paper ECG: Baseline (Day -49) to Day 92; Digital ECG: Baseline (Day 1) to Day 92
measure: Change from Baseline in Heart Rate by 12-Lead ECG in Paper and Digital Recordings
timeFrame: 12-lead paper ECG: Baseline (Day -49) to Day 92; Digital ECG: Baseline (Day 1) to Day 92
measure: Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs
timeFrame: Day 1 through 92 days after a single dose of study drug
measure: Number of Abnormal Findings for Ophthalmic Assessment (Ophthalmic Examination and Slit-lamp Examination) for Placebo and Cohorts 4 to 6 at Follow-up Visit
timeFrame: Follow-up Visit (Day 57)
measure: Intraocular Pressure at Screening for Placebo and Cohorts 4 to 6
timeFrame: Screening (Day -49)
measure: Intraocular Pressure at Day 29 for Placebo and Cohorts 4 to 6
timeFrame: Day 29
measure: Intraocular Pressure at Day 92 for Placebo and Cohorts 4 to 6
timeFrame: Day 92
measure: Number of Participants With Injection Site Reactions
timeFrame: Day 1
measure: Visual Analogue Scale (VAS) Pain Score for Site Reaction Pain
timeFrame: Day 1 (within 24 hours after end of infusion)
measure: Number of Participants With Suicidal Ideation and Suicidal Behavior Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Screening (Day -49) through 92 days after a single dose of study drug
measure: Number of Participants With Montreal Cognitive Assessment (MoCA) Total Score at Screening (Day -1)
timeFrame: Screening (Day -1)
measure: Number of Participants With MoCA Total Score at Day 92
timeFrame: Day 92
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of MEDI1341
timeFrame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
measure: Time to Maximum Serum Concentration (tmax) of MEDI1341
timeFrame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
measure: Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC0-t) of MEDI1341
timeFrame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
measure: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of MEDI1341
timeFrame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
measure: Terminal Half-life (t1/2λz) of MEDI1341
timeFrame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
measure: Serum Clearance (CL) of MEDI1341
timeFrame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
measure: Volume of Distribution at Steady State (Vss) of MEDI1341
timeFrame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
measure: Mean Residence Time (MRT) of MEDI1341
timeFrame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
measure: Percentage Change From Baseline in Plasma Concentrations of Total α-synuclein
timeFrame: Baseline (Day 1 predose) through Day 92
measure: Percentage Change From Baseline in Cerebrospinal Fluid Concentrations of Free α-synuclein
timeFrame: Baseline (Day 1 predose) and Day 29
measure: Percentage of Participants With Positive Antidrug Antibodies (ADAs) to MEDI1341 by Titer Levels at Day 92
timeFrame: Day 92
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Madison
country: United States
facility: Research Site
state: Wisconsin
Study officials:
affiliation: Covance Dallas CRU, USA
name: Jeanelle Kam, MD, CPI
role: PRINCIPAL_INVESTIGATOR
affiliation: Covance Madison CRU, USA
name: John E Blanchard, MD
role: PRINCIPAL_INVESTIGATOR
References: