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
- Trial ID
- 2022-500292-31-00
- Protocol
- ACI-7104-PD-2103
- Sponsor
- AC Immune S.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and **tolerability** of the investigational vaccine ACI-7104.056 in patients with early stages of idiopathic Parkinson's Disease. Additionally, the study aims to assess the **immunogenicity** by measuring the antibody response induced by the vaccine in serum. These objectives are clinically relevant as they provide critical information on the vaccine's potential to be safely administered and its ability to elicit an immune response, which are essential steps in the development of a therapeutic intervention for Parkinson's Disease.
Secondary objectives include:
- Assessing the pharmacodynamic effect of the study vaccine on **alpha-synuclein** related blood and/or cerebrospinal fluid biomarkers, including pathogenic alpha-synuclein oligomer species.
- Evaluating the effect of the study vaccine on **Dopamine Transporter-Single Photon Emission Computerized Tomography (DaT-SPECT)** imaging.
- Assessing the clinical effects of the study vaccine on the **Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III** score.
Participants
The clinical trial involves a total of **29 participants** diagnosed with early stages of **idiopathic Parkinson's Disease**. The study population includes both male and female subjects, aged between 40 and 75 years, with a body weight ranging from 45 kg to 110 kg and a body mass index of 18 to 34 kg/m². Participants are required to be on a stable monotherapy treatment with L-Dopa at 300 mg per day for at least three months prior to baseline. The trial population was selected based on a confirmed diagnosis of early idiopathic Parkinson's Disease, with motor symptoms present for no more than two years at screening. Subjects must have a centrally read screening brain DaT-SPECT consistent with Parkinson's Disease and be classified within Modified Hoehn-Yahr Stage I to II. Lifestyle considerations include the ability to understand and comply with the study protocol, and for female participants, specific contraceptive measures are required if they are of childbearing potential. The trial includes a vulnerable population, ensuring that all participants can provide informed consent and are willing to adhere to the study requirements.
Plans and Procedures
The clinical trial is designed as an adaptive, **Phase 2**, double-blind, randomized, placebo-controlled, multicenter study. The primary objective is to evaluate the safety, tolerability, immunogenicity, and pharmacodynamic effects of the investigational product, ACI-7104.056, in patients with early stages of **Parkinson's disease**. The trial is expected to last until January 31, 2028, with recruitment having commenced on September 26, 2022. Participants will be randomly assigned to receive either the study vaccine or a placebo, with the study vaccine administered via **intramuscular injection**. The placebo is an adjuvanted solution matching the study vaccine formulation.
The trial will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be confirmed based on criteria such as a diagnosis of early idiopathic Parkinson's disease, age between 40 and 75 years, and specific treatment and health conditions. Follow-up visits will occur at regular intervals to monitor safety and efficacy, including assessments of adverse events, physical and neurological examinations, and laboratory tests. The end-of-study visit will conclude the participant's involvement, with final evaluations conducted to assess the primary and secondary endpoints.
Participants are expected to be involved in the study for approximately 108 weeks, including the safety follow-up period. Conditions that may lead to early termination from the study include the occurrence of significant adverse events, non-compliance with the study protocol, or withdrawal of consent. The primary endpoints focus on safety and tolerability, as well as the immunogenicity of the vaccine, while secondary endpoints include changes in fluid biomarkers and clinical scores related to Parkinson's disease. The study aims to provide valuable insights into the potential benefits and risks of ACI-7104.056 in this patient population.
Treatment
The clinical trial involves the administration of **ACI-7104.056**, an investigational vaccine designed for patients in the early stages of **Parkinson's disease**. This experimental medication is formulated as an **injection** and contains the active substance **PD01B**, classified as a structurally diverse substance - vaccine. The vaccine is administered via the **intramuscular** route. The dosing regimen includes a maximum daily dose of 75 µg microgram(s) and a total maximum dose of 450 µg microgram(s) over a treatment period of 74 days. The study aims to evaluate the safety, tolerability, immunogenicity, and pharmacodynamic effects of this vaccine.
A **placebo** is also utilized in this study, specifically an adjuvanted solution known as PBS-ALH02, which matches the formulation of the study vaccine. The placebo serves as a control to assess the effects of the investigational vaccine. The pharmaceutical form and route of administration for the placebo are designed to mimic those of the experimental treatment, ensuring blinding in this double-blind, randomized, placebo-controlled trial.
Additionally, the study employs **DaTSCAN 74 MBq/ml solution for injection** as an auxiliary treatment. This solution contains the active substance **Ioflupane (123I)**, a chemical used for diagnostic imaging. DaTSCAN is administered via the **intravenous** route, with a maximum daily and total dose of 185 MBq megabecquerel(s). The use of DaTSCAN is intended to support the evaluation of the pharmacodynamic effects of the investigational vaccine by providing imaging data relevant to the study's objectives.
Efficacy
The efficacy of the investigational product ACI-7104.056 in patients with early stages of **Parkinson's disease** will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on safety and tolerability, including adverse events, results from physical and neurological examinations, global assessment of tolerability, vital signs, brain MRI, electrocardiogram, and routine laboratory tests in blood and urine. Additionally, suicidality will be measured using the Columbia Suicide Severity Rating Scale. Immunogenicity will be evaluated by assessing the antibody response induced by the study vaccine.
Secondary endpoints will include the measurement of absolute levels and changes from baseline in a-synuclein-related fluid biomarkers, such as pathogenic a-synuclein oligomer species and differentially phosphorylated synuclein species, in collected blood and/or cerebrospinal fluid samples. Changes from baseline in DaT-SPECT imaging will be assessed at 48 weeks and 100 weeks. Furthermore, absolute values and changes from baseline in the MDS-UPDRS Part III score will be evaluated over a period of 100 weeks.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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 subject 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.
- Subjects can understand the informed consent form, are able and willing to provide written 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 subjects 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 subjects 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 subjects 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 subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria
- 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.
- Known carriers of certain familial PD gene mutations (PRKN, PINK1, DJ1, LRRK2).
- History of PD-related freezing episodes or falls.
- History of brain surgery or any neurosurgical procedures.
- Reside in a nursing home or assisted care facility.
- 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.
- 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.
- 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.
- 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 subject (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.
- Subjects with known hypersensitivity to the study vaccine or placebo components.
- Subjects who previously received a vaccination (ie, influenza vaccine 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.
- Subjects being treated with any anticoagulants or antiplatelet drugs, except aspirin at doses of 100 mg daily or lower.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 26 Sept 2022 | 71 |
 Spain | Recruiting | 26 Sept 2022 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ACI-7104.056 | Test | INJECTION | INTRAMUSCULAR | 75 | 74 | PRD9742584 |
DaTSCAN 74 MBq/ml solution for injection | Other | SOLUTION FOR INJECTION | INTRAVENOUS | 185 | 1 | PRD317577 |
Placebo (PBS-ALH02), adjuvanted solution matching the study vaccine formulation | Placebo | N/A | — | — | — | N/A |