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Completed

NCT Number: NCT03272165

Single Ascending Dose Study of MEDI1341 in Healthy Volunteers

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.

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Key information

Conditions

Parkinson's Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Movement Disorders Nervous System Diseases Neurodegenerative Diseases Parkinson Disease Parkinsonian Disorders Synucleinopathies

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site, Dallas, Texas, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

MEDI1341

Drug

Participants will receive IV infusion of MEDI1341 doses as stated in the arms' description.

Other names: TAK-341

Placebo

Drug

Participants will receive IV infusion of placebo matched to MEDI1341.

Primary outcomes

  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

    Time frame: Day 1 through 92 days after a single dose of study drug

    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

  2. Number of Participants With Abnormal Vital Signs, Physical and Neurological Examinations, and Body Weight Measurements Reported as TEAEs

    Time frame: Day 1 through 92 days after a single dose of study drug

    Vital signs assessment included body temperature, respiration rate, pulse rate, and blood pressure. Participants with abnormal vital signs, physical and neurological examinations, and body weight measurements reported as TEAEs are reported.

  3. 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)

    Time frame: 12-lead paper ECG: Baseline (Day -49) to Day 92; Digital ECG: Baseline (Day 1) to Day 92

    Changes from baseline in 12-Lead ECG data in paper recordings (PR interval, QRS duration, QT interval, and QTcF interval) and digital recordings (PR interval, QRS duration, QT interval, QTcF interval, and RR interval) are reported.

  4. Change from Baseline in Heart Rate by 12-Lead ECG in Paper and Digital Recordings

    Time frame: 12-lead paper ECG: Baseline (Day -49) to Day 92; Digital ECG: Baseline (Day 1) to Day 92

    Change from baseline in heart rate by 12-Lead ECG in paper and digital recordings are reported.

  5. Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs

    Time frame: Day 1 through 92 days after a single dose of study drug

    Laboratory assessment included hematology, clinical chemistry, and urinalysis. Participants with abnormal laboratory parameters reported as TEAEs are reported.

  6. Number of Abnormal Findings for Ophthalmic Assessment (Ophthalmic Examination and Slit-lamp Examination) for Placebo and Cohorts 4 to 6 at Follow-up Visit

    Time frame: Follow-up Visit (Day 57)

    Number of abnormal findings for ophthalmic assessment (ophthalmic examination and slit-lamp examination) at follow-up visit (Day 57) are reported.

  7. Intraocular Pressure at Screening for Placebo and Cohorts 4 to 6

    Time frame: Screening (Day -49)

    Intraocular pressure at Screening (Day -49) is reported.

  8. Intraocular Pressure at Day 29 for Placebo and Cohorts 4 to 6

    Time frame: Day 29

    Intraocular pressure at Day 29 is reported.

  9. Intraocular Pressure at Day 92 for Placebo and Cohorts 4 to 6

    Time frame: Day 92

    Intraocular pressure at Day 92 is reported.

  10. Number of Participants With Injection Site Reactions

    Time frame: Day 1

    Participants who had injection site reactions (bleeding, bruising, erythema, swelling, or induration) on Day 1 are reported.

  11. Visual Analogue Scale (VAS) Pain Score for Site Reaction Pain

    Time frame: Day 1 (within 24 hours after end of infusion)

    The VAS (0 to 10 cm) was used to describe reaction site pain. The score 0 means 'no pain at all' and 10 score means 'worst pain imaginable'. The higher the VAS score, the greater the reaction site pain experienced.

  12. Number of Participants With Suicidal Ideation and Suicidal Behavior Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)

    Time frame: Screening (Day -49) through 92 days after a single dose of study drug

    The C-SSRS is a scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviours, and has a binary response (yes/no).

    • Suicidal Ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent.
    • Suicidal Behaviour: a "yes" answer to any of 5 suicidal behaviour questions: preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt (non-fatal), completed suicide.

  13. Number of Participants With Montreal Cognitive Assessment (MoCA) Total Score at Screening (Day -1)

    Time frame: Screening (Day -1)

    The MoCA is s standardized cognitive screening tool for mild cognitive impairment and dementia. The total score was used as outcome measure and this score ranges from 0-31, with higher scores representing better cognitive ability and scores below 26 were considered as cognitive dysfunction.

  14. Number of Participants With MoCA Total Score at Day 92

    Time frame: Day 92

    The MoCA is s standardized cognitive screening tool for mild cognitive impairment and dementia. The total score was used as outcome measure and this score ranges from 0-31, with higher scores representing better cognitive ability and scores below 26 were considered as cognitive dysfunction.

Secondary outcomes

  1. Maximum Observed Serum Concentration (Cmax) of MEDI1341

    Time frame: 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

    The Cmax of MEDI1341 is reported.

  2. Time to Maximum Serum Concentration (tmax) of MEDI1341

    Time frame: 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

    The tmax of MEDI1341 is reported.

  3. Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC0-t) of MEDI1341

    Time frame: 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

    The AUC0-t of MEDI1341 is reported.

  4. Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of MEDI1341

    Time frame: 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

    The AUC0-∞ of MEDI1341 is reported.

  5. Terminal Half-life (t1/2λz) of MEDI1341

    Time frame: 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

    The t1/2λz of MEDI1341 is reported.

  6. Serum Clearance (CL) of MEDI1341

    Time frame: 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

    The CL of MEDI1341 is reported.

  7. Volume of Distribution at Steady State (Vss) of MEDI1341

    Time frame: 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

    The Vss of MEDI1341 is reported.

  8. Mean Residence Time (MRT) of MEDI1341

    Time frame: 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

    The MRT of MEDI1341 is reported.

  9. Percentage Change From Baseline in Plasma Concentrations of Total α-synuclein

    Time frame: Baseline (Day 1 predose) through Day 92

    Maximum change from baseline through Day 92 and change from baseline at Day 92 in plasma concentrations of total α-synuclein are reported.

  10. Percentage Change From Baseline in Cerebrospinal Fluid Concentrations of Free α-synuclein

    Time frame: Baseline (Day 1 predose) and Day 29

    Change from baseline in cerebrospinal fluid concentrations of free α-synuclein is reported.

  11. Percentage of Participants With Positive Antidrug Antibodies (ADAs) to MEDI1341 by Titer Levels at Day 92

    Time frame: Day 92

    Percentage of participants with positive ADAs to MEDI1341 by titer levels are reported.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Catalent
  • Covance
  • MMS Holdings, Inc
  • Takeda

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2021
Study completion
2021
First posted
Sep 5, 2017
Registry last updated
Jun 9, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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