| Eligibility |
Inclusion criteria:
1. Subjects must be aged 40 to 85 years, inclusive, on the day of randomization.
2. 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)
3. PD should be stage 1 to 3 using the Hoehn and Yahr scale as modified (Goetz et al
2004).
4. 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).
5. 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.
6. Subjects may be male or female. Female subjects must of non-childbearing potential
(postmenopausal and/or surgically sterile.
7. 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.
8. 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.
9. 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.
10. 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.)
11. Subjects must be able to read, write, and speak fluently in English and/or Spanish.
12. 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.
13. Subjects must have a MoCA total score of = 24.
Exclusion Criteria:
1. In the opinion of the investigator, a recent clinically significant illness (other
than PD), infection, medical/surgical procedure, or significant trauma within 30 days
prior to screening, or between screening and randomization, that is likely to
deteriorate, compromise the subject's safety or ability to complete the study, or
compromise the interpretation of the study results (Note: a history of coronavirus
disease 2019 [COVID 19] infection with unresolved medical sequelae would be considered
exclusionary.)
2. 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
3. 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)
4. 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
5. 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
6. History of epilepsy or seizures, except febrile childhood seizures
7. History of transient ischemic attack or stroke or any unexplained loss of
consciousness within 1 year prior to screening or between screening and randomization
8. 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
9. A diagnosis of intellectual disability (intellectual developmental disorder) or mental
retardation, or significant inherited cognitive impairment
10. 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
11. 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
12. 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
13. 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
14. Moderate or severe congestive heart failure, or known ejection fraction < 40%
15. 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
16. 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
17. History of allergy/hypersensitivity to immunizations or immunoglobulins
18. Any condition that, in the opinion of the investigator or medical monitor, makes the
subject unsuitable for the study
19. Requires treatment with another monoclonal antibody
20. Use of any investigational medicine, device, or biologic within 3 months or 5
half-lives of that intervention (whichever is longer) prior to screening
21. Previous allogeneic bone marrow or stem cell transplant
22. Use of typical or atypical antipsychotic medication, or other medication with dopamine
antagonist properties (eg, metoclopramide, domperidone), within 6 months prior to
randomization
23. Use of immunosuppressive medication within 6 months prior to randomization. (Note:
Inhaled and topical corticosteroids are permitted. Low-dose systemic corticosteroids
[< 10 mg per day prednisone or equivalent], for autoimmune disease that is considered
to be quiescent, in remission, or otherwise well controlled are permitted). Other
immunosuppressive drugs and biologics are contraindicated.
24. Received non-leukocyte depleted whole blood transfusion within 6 months prior to
screening
25. Received any commercially available vaccine within 30 days prior to randomization.
(Note: for COVID-19 vaccines authorized by the FDA for emergency use, this time frame
applies from last vaccination or booster dose, whichever is required to consider
vaccination complete in line with applicable guidance.)
26. Participation in another study investigating:
1. Active or passive immunization against a synuclein for PD, at any time prior to
screening, or
2. Immunoglobulin G therapy within 6 months before screening
27. Any clinically significant abnormality as determined by investigator at screening or
between screening and randomization in physical examination, vital signs, ECG, or
clinical laboratory test results that may compromise the subject's safety or ability
to complete the study or compromise the interpretation of the study results
28. Presence of any of the following MRI contraindications: pacemaker; cardiac
defibrillator; spinal cord or vagus nerve stimulator; aneurysm clip; artificial heart
valve; recent (within one year) coronary or carotid stent; ear implant; CSF shunt;
other implanted medical device (eg, insulin pump); metal fragments or foreign objects
in the eyes, skin, or body; claustrophobia that would contraindicate a brain MRI scan
29. Brain MRI findings (or historical radiologic reports, if available) that show evidence
of clinically significant structural brain disease which, in the opinion of the
investigator, contraindicates performance of LP
30. Any spinal abnormality or other aspects (eg, tattoos) or other clinical findings
(papilledema seen with ophthalmoscopy) that may complicate or contraindicate LP, as
judged by the investigator
31. Ophthalmic abnormalities. The following are considered exclusionary:
1. Congenital or acquired ophthalmic conditions (primary or secondary) that are
considered poorly controlled within the last 12 months prior to screening, with
or without treatment, or otherwise expected to lead to significant deterioration
in visual acuity in the next 6 months after randomization
2. Specific ophthalmic conditions:
i. Current or past history of inflammation affecting the uveal tract or sclera ii.
Diabetic retinopathy iii. Neovascular or exudative (wet) form of age-related macular
degeneration iv. Active central serous retinopathy (central serous chorioretinopathy)
v. Subjects with active autoimmune disease vi. Subjects taking immunosuppressive drugs
(other than low doses of systemic steroids [< 10 mg per day of prednisone equivalent],
for autoimmune disease that is considered to be inactive, in remission, or otherwise
well-controlled). Other immunosuppressive drugs are contraindicated.
vii. Mature cataracts (Grade = 4 per the Lens Opacities Classification System III) or
lower grade cataracts that are otherwise considered by the examining ophthalmologist
to prevent adequate examination of the uveal tract or posterior ocular segment. (Note:
Previous cataract surgery or an age-related cataract with age-appropriate lens
opacification and no other important identified secondary causes [eg, diabetes,
corticosteroids, vitamin deficiencies, trauma, radiation, or systemic fluid and
electrolyte disturbances] is not necessarily exclusionary.)
32. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentrations >1.5
× the upper limit of normal (ULN) at screening, or between screening and baseline
33. Estimated creatinine clearance < 50 mL/min or creatinine > 1.5 × ULN at screening
34. Clinically significant vital sign abnormalities at screening or on Day 1, defined as
(a) systolic blood pressure = 160 mmHg, (b) diastolic blood pressure = 90 mmHg (blood
pressure assessed at rest; may be repeated up to 3 times), or (c) pulse rate < 45 or >
100 beats per minute (at rest)
35. Clinically significant abnormality in ECG rhythm, conduction or morphology at
screening or between screening and randomization, including but not limited to:
- Clinically significant PR (PQ) interval prolongation (PR > 220 msec)
- Intermittent second or third degree atrioventricular (AV) block (AV block II
Mobitz Type I, Wenckebach, while asleep or in deep rest is not exclusionary)
- Bundle branch block or intraventricular conduction delay with QRS interval
duration = 120 msec
- A Fridericia's corrected QT (QTcF) interval measurement > 470 msec, or a
shortened QTcF < 340 msec, at screening or between screening and randomization;
or a family history of long or short QT syndrome
36. Positive serologic findings for human immunodeficiency virus (HIV) antibodies,
hepatitis B surface antigen, or hepatitis C virus antibodies, with relevant
confirmatory testing conducted, where applicable, in accordance with Centers for
Disease Control and Prevention guidance for HIV and viral hepatitis
37. Current blood clotting or bleeding disorder, including clinically significant abnormal
findings in laboratory tests of coagulation
38. Poor venous access, such that IV drug delivery or PK/safety blood sampling would be
difficult
39. Donation of blood or plasma within 2 months prior to screening and until 2 months
after the final follow-up visit
40. A positive serum pregnancy test result at screening or prior to randomization
41. Urine drug screen positive for a drug of abuse (except for permitted, prescribed
opiates and /or benzodiazepines). A urine drug screen positive for cannabinoids is
exclusionary unless there is a documented legitimate medical reason for the subject's
cannabinoid use (eg, chronic pain) or the investigator and medical monitor agree that
the subject can abstain from use for the duration of the study.
42. Current employment by the sponsor (AstraZeneca) or by a contract research organization
or clinical study site participating in this study, or a first-degree relative of an
AstraZeneca employee or of an employee at a participating contract research
organization or clinical study site
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