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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AC Immune S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 May 2023 → ongoing

Decision date (initial)

2022-10-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AC Immune S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Others, Safety

To assess the safety and tolerability of the study vaccine (ACI-7104.056).
To assess the antibody response induced by the study vaccine in serum.

Secondary objectives 3

1. • To assess the pharmacodynamic effect of the study vaccine on alpha-synuclein (a-syn) related blood and/or cerebrospinal fluid (CSF) biomarkers including pathogenic a-syn oligomer species.
2. • To assess the effect of the study vaccine on Dopamine Transporter-Single Photon Emission Computerized Tomography (DaT-SPECT) imaging.
3. • To assess the clinical effects of the study vaccine on Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score.

Conditions and MedDRA coding

Early stages of idiopathic Parkinson's Disease

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Paul Ehrlich Institute

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. 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.
3. Male or female.
4. Aged ≥40 to ≤75 years.
5. Body weight range of ≥45 kg to ≤110 kg (99 to 242 lbs) and a body mass index of ≥18 to ≤34 kg/m2
6. Modified Hoehn-Yahr Stage I to II.
7. A centrally read screening brain DaT-SPECT consistent with PD.
8. 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.
9. 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 14

1. 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.
2. Known carriers of certain familial PD gene mutations (PRKN, PINK1, DJ1, LRRK2).
3. History of PD-related freezing episodes or falls.
4. History of brain surgery or any neurosurgical procedures.
5. Reside in a nursing home or assisted care facility.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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)
11. Current, or history of, alcohol or drug (including cannabis) abuse or other dependence (except nicotine dependence) within 12 months before screening.
12. Subjects with known hypersensitivity to the study vaccine or placebo components.
13. 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.
14. Subjects being treated with any anticoagulants or antiplatelet drugs, except aspirin at doses of 100 mg daily or lower.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety and Tolerability: Adverse events; physical and neurological examination results; global assessment of tolerability; vital signs; brain MRI; ectrocardiogram; routine laboratory tests (eg, hematology and biochemistry evaluation) in blood and urine; suicidality as measured with the Columbia Suicide Severity Rating Scale.
2. Immunogenicity: Antibody response induced by the study vaccine.

Secondary endpoints 3

1. Absolute levels and change from baseline in a-syn related fluid biomarkers, including pathogenic a-syn oligomer species and/or differentially phosphorylated synuclein species, in any collected blood and/or CSF sample.
2. Change from baseline in DaT-SPECT at 48 weeks and 100 weeks.
3. Absolute values and change from baseline in the MDS-UPDRS Part III score over 100 weeks.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AC Immune S.A.

Sponsor organisation

AC Immune S.A.

Address

Innovation Park

City

Lausanne

Postcode

1015

Country

Switzerland

Scientific contact point

Organisation

AC Immune S.A.

Contact name

Clinical Trial Information

Public contact point

Organisation

AC Immune S.A.

Contact name

Clinical Trial Information

Third parties 11

Locations

2 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 49 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications