An adaptive, Phase 2, double-blind, randomized, placebo-controlled, multicenter study to evaluate the safety, tolerability, immunogenicity, and pharmacodynamic effects of ACI-7104.056 in patients with early stages of Parkinson’s disease

Prior treatment

• History of and/or screening brain MRI scan indicative of, clinically significant abnormality including but not limited to prior hemorrhage or infarct >1 cm3 or >3 lacunar infarcts.
• Clinically significant concomitant disease or condition within 6 months prior to screening, or as specified below, that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the study participant (for details refer to protocol)
• Current, or history of, alcohol or drug (including cannabis) abuse or other dependence (except nicotine dependence) within 12 months before screening.
• Participants who previously received a vaccination (ie, influenza treatment and COVID-19) within the last 4 weeks prior to randomization, or standard-of-care immunizations (eg, tetanus, herpes zoster, pneumococcal pneumonia) within the last 2 weeks prior to randomization.
• Participants being treated with any anticoagulants or antiplatelet drugs, except aspirin at doses of 100 mg daily or lower.

Other illness

• Medical history indicating a Parkinsonian syndrome other than idiopathic PD, including but not limited to, progressive supranuclear palsy, multiple system atrophy, drug-induced parkinsonism, essential tremor, vascular parkinsonism, primary dystonia.
• A history of cancer within 5 years of baseline with the exception of fully excised non-melanoma skin cancers or nonmetastatic prostate cancer that has been stable for at least 6 months, or cervical intraepithelial neoplasia stage I uterine cancer.
• Diagnosis of a significant central nervous system disease other than PD (including but not limited to Huntington’s disease, normal pressure hydrocephalus, cerebrovascular disease including stroke, fronto-temporal dementia, Alzheimer’s disease, dementia with Lewy bodies, multiple sclerosis, brain tumor); history of repeated head injury; history of epilepsy or seizure disorder other than febrile seizures as a child.
• Presence of psychiatric symptoms (eg, confusion, hallucination, delusion, excitation, delirium, abnormal behavior at screening and baseline). Note: mild depression, depressive mood, or mild anxiety arising in the context of PD are not exclusionary.
• Participants with known hypersensitivity to the study treatment or placebo components.
• History of PD-related freezing episodes or falls.
• History of brain surgery or any neurosurgical procedures.

Other

• Reside in a nursing home or assisted care facility.
• Known carriers of certain familial PD gene mutations (PRKN, PINK1, DJ1, LRRK2).

• Confirmed diagnosis of clinically established early idiopathic PD using the modified Movement. Disorder Society criteria, after excluding any other known or suspected cause of PD. The presence of motor symptoms should not be of more than 2 years at screening.
• Monotherapy treatment with L-Dopa at 300 mg per day, with a stable dose prior to baseline for 3 months. The participant has a reasonably low likelihood of requiring dose adjustment within the next 6 to 12 months after enrolment. Any exception to this rule has to be previously agreed with the Sponsor medical monitor.
• Male or female.
• Aged ≥40 to ≤75 years.
• Body weight range of ≥45 kg to ≤110 kg (99 to 242 lbs) and a body mass index of ≥18 to ≤34 kg/m2
• Modified Hoehn-Yahr Stage I to II.
• A centrally read screening brain DaT-SPECT consistent with PD.
• Participants can understand the informed consent form, are able and willing to provide documented informed consent, and can be expected to comply with the study protocol according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and local regulations.
• Female participants must be postmenopausal for at least 1 year and/or surgically sterilized, or, if they are woman of childbearing potential or not postmenopausal, they must have a negative blood pregnancy test at screening and be willing to use highly effective methods of contraception from the screening visit until the end of safety follow-up period (approximately 108 weeks). Male participants in the trial with female partners of childbearing potential are required to use barrier methods of contraception (condoms with spermicide) in addition to contraceptive measures used by female partners during the whole study duration. Men must refrain from donating sperm during this same period. The female partners of male participants should use a highly effective method of contraception with a failure rate of less than 1% per year from screening until the end of the safety follow-up period (approximately 108 weeks). The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the partcipant. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.