Single Ascending Dose Study of MEDI1341 in Healthy Volunteers

NCT03272165 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: D6340C00001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Parkinson's Disease

Keywords

Healthy Volunteers; Safety; Tolerability; Pharmacokinetics; Pharmacodynamics; Immunogenicity

Outcome Measures

Primary Outcomes (14)

• 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.

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

• 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.

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

• 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.

  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

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

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

• 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.

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

• 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.

  Follow-up Visit (Day 57)

• Intraocular Pressure at Screening for Placebo and Cohorts 4 to 6

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

  Screening (Day -49)

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

  Intraocular pressure at Day 29 is reported.

  Day 29

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

  Intraocular pressure at Day 92 is reported.

  Day 92

• Number of Participants With Injection Site Reactions

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

  Day 1

• 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.

  Day 1 (within 24 hours after end of infusion)

• 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.

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

• 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.

  Screening (Day -1)

• 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.

  Day 92

Secondary Outcomes (11)

• Maximum Observed Serum Concentration (Cmax) of MEDI1341

  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

• Time to Maximum Serum Concentration (tmax) of MEDI1341

  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

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

  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

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

  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

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

  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

Study Arms (7)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Cohort 1: MEDI1341 Dose 1

EXPERIMENTAL

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

Drug: MEDI1341

Cohort 2: MEDI1341 Dose 2

EXPERIMENTAL

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

Drug: MEDI1341

Cohort 3: MEDI1341 Dose 3

EXPERIMENTAL

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

Drug: MEDI1341

Cohort 4: MEDI1341 Dose 4

EXPERIMENTAL

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

Drug: MEDI1341

Cohort 5: MEDI1341 Dose 5

EXPERIMENTAL

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

Drug: MEDI1341

Cohort 6: MEDI1341 Dose 6

EXPERIMENTAL

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

Drug: MEDI1341

Interventions

MEDI1341 DRUG

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

Also known as: TAK-341

Cohort 1: MEDI1341 Dose 1; Cohort 2: MEDI1341 Dose 2; Cohort 3: MEDI1341 Dose 3; Cohort 4: MEDI1341 Dose 4; Cohort 5: MEDI1341 Dose 5; Cohort 6: MEDI1341 Dose 6

Placebo DRUG

Participants will receive IV infusion of placebo matched to MEDI1341.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Covance: collaborator
• MMS Holdings, Inc: collaborator
• Catalent: collaborator
• Takeda: collaborator

Study Sites (2)

Research Site

Dallas, Texas, 75247, United States

Location

Research Site

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Jeanelle Kam, MD, CPI

  Covance Dallas CRU, USA

  PRINCIPAL INVESTIGATOR

• John E Blanchard, MD

  Covance Madison CRU, USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are randomized to one of two groups within a cohort of 8 participants (N=6 MEDI1341; N=2 placebo)

Study Record Dates

• First Submitted: June 29, 2017
• First Posted: September 5, 2017
• Study Start: October 17, 2017
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: June 9, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved, AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsor tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

US (2)