Multiple Ascending Dose Study of MEDI1341 in Patients With Parkinson's Disease

NCT04449484 | Completed Phase 1 FDA Drug

• 1 other identifier: D6340C00002
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 5

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled study of multiple ascending iv doses of MEDI341 in male and female subjects with Parkinson's Disease.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (17)

• Adverse Events

  Incidence, Nature, Severity and Seriousness of adverse events from screening

  28 weeks

• Vital Signs

  Change from baseline in Blood Pressure measured in millimetres of Mercury

  21 weeks

• Oral Body Temperature

  Change from baseline in body temperature measured in degrees Celcius

  21 weeks

• Body Weight

  Change from baseline measured in Kilograms

  21 weeks

• Safety Laboratory Tests

  Incidence from baseline in abnormal laboratory test results

  21 weeks

• Electrocardiograms

  Change from baseline in ECG rythm

  21 weeks

• Ophthalmic assessments

  Incidence from baseline in abnormal ocular findings

  21 weeks

• Suicidal Ideation

  Evaluation of presence or absence of suicidal ideation as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)

  21 weeks

• Cognitive impairment

  Change from baseline in the total score of the Montreal Cognitive assessment; a 30-point test (the higher the score, the better the cognition)

  21 weeks

• Electrocardiograms

  Change from baseline in ECG heart rate

  21 weeks

• Electrocardiograms

  Change from baseline in ECG conduction

  21 weeks

• Electrocardiograms

  Change from baseline in ECG PR interval

  21 weeks

• Electrocardiograms

  Change from baseline in ECG QRS interval

  21 weeks

• Electrocardiograms

  Change from baseline in ECG RR interval

  21 weeks

• Electrocardiograms

  Change from baseline in ECG QT interval

  21 weeks

• Electrocardiograms

  Change from baseline in ECG QTcF interval

  21 weeks

• Suicidal Behaviour

  Evaluation of presence or absence of suicidal behaviour as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)

  21 weeks

Study Arms (2)

MEDI1341

EXPERIMENTAL

3 doses given at 4 week intervals

Drug: MEDI1341

Placebo

PLACEBO COMPARATOR

3 doses given at 4 week intervals

Other: Placebo

Interventions

MEDI1341 DRUG

Intravenous infusion over 60 minutes

Also known as: TAK-341

MEDI1341

Placebo OTHER

Intravenous infusion over 60 minutes

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be aged 40 to 85 years, inclusive, on the day of randomization.
• Meet criteria for a diagnosis of mild-to-moderate idiopathic PD according to the United Kingdom Parkinson's Disease Society Brain Bank criteria (Hughes et al 1992)
• PD should be stage 1 to 3 using the Hoehn and Yahr scale as modified (Goetz et al 2004).
• Subjects receiving medications for PD should have been on a stable dosing regimen of their medication(s) for ≥ 1 month before randomization, with no expectation of a need to change the medications or dosing regimen for the duration of the study, barring unforeseen circumstances. (For subjects who are not currently receiving medications to treat PD, there should be no expectation of a need to initiate these for the duration of the study).
• Subjects must have a body weight of 45 to 120 kg, inclusive, and a body mass index of 18 to 34 kg/m2, inclusive at screening and at check-in for the first infusion.
• Subjects may be male or female. Female subjects must of non-childbearing potential (postmenopausal and/or surgically sterile.
• Postmenopausal women must have had ≥ 12 months of spontaneous amenorrhea (with a follicle-stimulating hormone \[FSH\] concentration ≥ 26 mIU/mL in women ≤ 60 years of age; women \> 60 years of age do not require an FSH test) and must have had a negative serum pregnancy test result at screening.
• Surgically sterile women are defined as those who have had a hysterectomy, bilateral ovariectomy (oophorectomy), salpingectomy, or bilateral tubal ligation. Women who are surgically sterile must provide documentation of the procedure by an operative report, ultrasound, or other verifiable medical documentation.
• Men who are biologically capable of fathering children must agree and commit to use an adequate form of double-barrier contraception for the duration of the treatment period and for 5 half lives (100 days) after the last administration of study intervention. A male subject is considered capable of fathering children even if his sexual partner is sterile or using contraceptives.
• Men who are biologically capable of fathering children must also agree to refrain from sperm donation for the duration of the treatment period and for 5 half-lives or 90 days (whichever is longer) after the last administration of study intervention.
• Subjects must, in the investigator's opinion, understand the nature of the study and must provide signed and dated written informed consent before the conduct of any study-related procedures.
• Subjects must, in the opinion of the investigator, be able to participate in all scheduled evaluations, likely to be compliant, and likely to complete all required tests, including magnetic resonance imaging (MRI) brain scans and lumbar punctures (LPs). (Note: The investigator should assess the physical and functional needs of the subject at screening, as participation in the study may be contingent upon the availability and willingness of a caregiver to attend with the subject at all study visits.)
• Subjects must be able to read, write, and speak fluently in English and/or Spanish.
• Subjects must agree not to post any personal medical data related to the study or information related to the study on any website or social media site (eg, Facebook, Twitter, Instagram, etc) until the study has been completed.
• Subjects must have a MoCA total score of ≥ 24.

You may not qualify if:

• Presence of a serious or unstable clinically significant illness, including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic or autoimmune disease (eg, multiple sclerosis), hematologic or other major disease, which, in the judgment of the investigator, is poorly controlled or otherwise likely to deteriorate, compromise the subject's safety or ability to complete the study, or compromise the interpretation of the study results
• Significant neurological disease affecting the CNS (other than PD) that, in the opinion of the investigator, may affect motor function or the ability to complete the study, including but not limited to progressive supranuclear palsy, multiple system atrophy (MSA; including MSA-P and MSA-C or other MSA terminology: striatonigral degeneration, olivopontocerebellar atrophy or autonomic failure), postencephalitic parkinsonism, metabolic diseases with parkinsonian signs and symptoms (eg, Wilson disease, manganese exposure) or other secondary forms of Parkinsonism, and ischemic or traumatic brain injury (including multiple episodes of head trauma, or head trauma resulting in protracted loss of consciousness within the 5 years prior to screening or between screening and randomization)
• Brain MRI scan that shows clinically significant evidence of malignant, ischemic, demyelinating, structural, or degenerative brain disease or has findings that compromise the safety of LP
• Has undergone surgery for the treatment of PD (eg, pallidotomy, deep brain stimulation, fetal tissue transplantation) or has undergone any other brain surgery at any time, even for non-PD conditions
• History of epilepsy or seizures, except febrile childhood seizures
• History of transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to screening or between screening and randomization
• Presence of any psychiatric disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V; APA 2013) or symptom if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of the study results, affect motor function assessment, or affect the subject's ability to complete the study
• A diagnosis of intellectual disability (intellectual developmental disorder) or mental retardation, or significant inherited cognitive impairment
• Suicidality, represented by answering "yes" to Question 4 or Question 5 on the C SSRS, indicating active suicidal ideation with any intent to act, during the subject's lifetime, as assessed at screening, or between screening and randomization
• Suicidal behavior such that a determination of "yes" is made on the Suicidal Behavior section of the C SSRS for "Actual Attempt," "Interrupted Attempt," "Aborted Attempt," or "Preparatory Acts or Behavior," during the subject's lifetime, as assessed at screening, or between screening and randomization
• History of alcohol or drug abuse or dependence (except nicotine dependence), as defined by the DSM-V, within 2 years prior to screening or between screening and randomization
• Within 1 year prior to screening, any of the following: myocardial infarction; hospitalization for congestive heart failure; hospitalization for, or symptoms of unstable angina; unexplained syncope
• Moderate or severe congestive heart failure, or known ejection fraction \< 40%
• Known significant structural heart disease (eg, significant valvular disease, hypertrophic cardiomyopathy) that is considered likely to lead to a deterioration of cardiac function over the course of the study
• History of cancer within 5 years prior to screening or between screening and randomization, with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin

Sponsors & Collaborators

• AstraZeneca: lead
• Takeda: collaborator

Study Sites (5)

Research Site

Long Beach, California, 90806, United States

Location

Research Site

Hallandale, Florida, 33009, United States

Location

Research Site

Atlanta, Georgia, 30331, United States

Location

Research Site

Farmington Hills, Michigan, 48334, United States

Location

Research Site

Spokane, Washington, 99202, 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

• Beth E. Safirstein, MD

  MD Clinical

  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: Subjects are randomised to one of two groups within a cohort of 12 subjects (N=9 MEDI1341; N=3 Placebo)

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: June 26, 2020
• Study Start: August 4, 2020
• Primary Completion: January 5, 2022
• Study Completion: January 5, 2022
• Last Updated: June 3, 2022

Record last verified: 2022-05

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 (5)