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CompletedNCT03272165Updated Jun 9, 2022

Single Ascending Dose Study of MEDI1341 in Healthy Volunteers

A Phase 1 interventional study of MEDI1341 and Placebo in Parkinson's Disease, sponsored by AstraZeneca. Completed at 2 sites in United States. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-06-09.

Sponsored by AstraZeneca · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Parkinson's Disease

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Keywords

  • Healthy Volunteers
  • Safety
  • Tolerability
  • Pharmacokinetics
  • Pharmacodynamics
  • Immunogenicity
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
50 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Participants will receive a single intravenous (IV) infusion of placebo matched to MEDI1341 and will be followed up for 13 weeks.

    Drug: Placebo

  • Experimental
    Cohort 1: MEDI1341 Dose 1

    Participants will receive a single IV infusion of MEDI1341 Dose 1 and will be followed up for 13 weeks.

    Drug: MEDI1341

  • Experimental
    Cohort 2: MEDI1341 Dose 2

    Participants will receive a single IV infusion of MEDI1341 Dose 2 and will be followed up for 13 weeks.

    Drug: MEDI1341

  • Experimental
    Cohort 3: MEDI1341 Dose 3

    Participants will receive a single IV infusion of MEDI1341 Dose 3 and will be followed up for 13 weeks.

    Drug: MEDI1341

  • Experimental
    Cohort 4: MEDI1341 Dose 4

    Participants will receive a single IV infusion of MEDI1341 Dose 4 and will be followed up for 13 weeks.

    Drug: MEDI1341

  • Experimental
    Cohort 5: MEDI1341 Dose 5

    Participants will receive a single IV infusion of MEDI1341 Dose 5 and will be followed up for 13 weeks.

    Drug: MEDI1341

  • Experimental
    Cohort 6: MEDI1341 Dose 6

    Participants will receive a single IV infusion of MEDI1341 Dose 6 and will be followed up for 13 weeks.

    Drug: MEDI1341

Interventions

  • DrugMEDI1341

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

    Also known as: TAK-341

  • DrugPlacebo

    Participants will receive IV infusion of placebo matched to MEDI1341.

05

What researchers measure

Primary outcomes

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

    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.

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

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

    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.

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

  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)

    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.

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

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

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

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

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

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

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

  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

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

    Time frame: Follow-up Visit (Day 57)

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

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

    Time frame: Screening (Day -49)

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

    Intraocular pressure at Day 29 is reported.

    Time frame: Day 29

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

    Intraocular pressure at Day 92 is reported.

    Time frame: Day 92

  10. Number of Participants With Injection Site Reactions

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

    Time frame: Day 1

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

    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.

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

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

    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.

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

  13. Number of Participants With Montreal Cognitive Assessment (MoCA) Total Score at 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.

    Time frame: Screening (Day -1)

  14. Number of Participants With MoCA Total Score at 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.

    Time frame: Day 92

Secondary outcomes

  1. Maximum Observed Serum Concentration (Cmax) of MEDI1341

    The Cmax of MEDI1341 is reported.

    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

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

    The tmax of MEDI1341 is reported.

    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

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

    The AUC0-t of MEDI1341 is reported.

    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

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

    The AUC0-∞ of MEDI1341 is reported.

    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

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

    The t1/2λz of MEDI1341 is reported.

    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

  6. Serum Clearance (CL) of MEDI1341

    The CL of MEDI1341 is reported.

    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

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

    The Vss of MEDI1341 is reported.

    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

  8. Mean Residence Time (MRT) of MEDI1341

    The MRT of MEDI1341 is reported.

    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

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

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

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

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

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

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

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

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

    Time frame: Day 92

06

Study locations

2 sites
  • Research Site
    Dallas, Texas 75247, United States
  • Research Site
    Madison, Wisconsin 53704, United States
07

References and documents

Individual participant data

Plan to share: Yes — Qualified researchers can request access to anonymised individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03272165
Lead sponsor
AstraZeneca
Collaborators
Covance, MMS Holdings, Inc, Catalent, Takeda
Responsible party
Sponsor
First posted
Sep 5, 2017
Start date
Oct 17, 2017
Primary completion
Mar 31, 2021
Completion
Mar 31, 2021
Last update
Jun 9, 2022

Study contacts

Jeanelle Kam, MD, CPI
principal investigator · Covance Dallas CRU, USA
John E Blanchard, MD
principal investigator · Covance Madison CRU, USA

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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