A phase 1b/2, multicenter, adaptive, double-blind, randomized, placebo-controlled study to assess the safety, tolerability, immunogenicity, and pharmacodynamic effects of ACI-24.060 in subjects with prodromal Alzheimer’s disease and in adults with Down syndrome (ABATE)

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

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

2 Nov 2022 → ongoing

Decision date (initial)

2022-08-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AC Immune SA - Switzerland

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Others, Safety

Study Part 1:
- To assess the safety and tolerability of ACI-24.060
Study Part 2:
• To assess the safety and tolerability of ACI-24.060.
• To assess the anti-Aβ antibody response generated by ACI-24.060 in serum.

Secondary objectives 3

1. Part 1: To assess the anti-amyloid β (Aβ) antibody response generated by ACI-24.060 in serum
2. Part 2: To assess the pharmacodynamic effect of ACI-24.060 on amyloid-related fluid biomarkers
3. Part 2: To assess the effect of ACI-24.060 on brain amyloid levels using PET scan.

Conditions and MedDRA coding

Alzheimer's disease

Study design 1 period

Regulatory references

Scientific advice from competent authorities

The Spanish Agency Of Medicines And Medical Devices, Medicines And Healthcare Products Regulatory Agency, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Sponsor will share participant’s coded data with other companies that help AC Immune SA conduct this study: Representatives of the Sponsor (including the contract research organization working with the Sponsor, monitors, third party vendors, and auditors), Advisory boards and institutional review boards/ethical committees, National health authorities, regulatory authorities and data protection authorities ensuring compliance with applicable laws, within and outside of the European Union/European Economic Area.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Part 1 : Age ≥50 and ≤85 years at screening.
2. Part 1 : Diagnosis of prodromal AD: MCI due to AD according to National Institute on Aging-Alzheimer’s Association (NIA-AA) criteria.
3. Part 1 : PET scan at screening consistent with the presence of amyloid pathology.
4. Part 1 : Clinical Dementia Rating (CDR)-Global Score of 0.5.
5. Part 1 : Subjects who in the opinion of the investigator are able to understand the details of the study and to provide written informed consent.
6. Part 1 : Subjects either not taking any marketed treatment for AD or receiving a stable dose of an acetylcholinesterase inhibitor (ACHEI) and/or memantine for at least 2 months prior to baseline.
7. Part 1 : Subjects cared for by a reliable spouse, informant, or study partner to assure compliance, assist with clinical assessments, and report safety issues, and spouse, informant or study partner consents to serve in this role.
8. Part 1 : Females who are either post-menopausal for at least 1 year and/or surgically sterilized, or females of childbearing potential or not post-menopausal 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 their participation. 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.
9. Part 1 : Subjects and study partners must be sufficiently proficient in the official language(s) of the country they are living in and able to comply with all study procedures, including lumbar punctures.
10. Part 2 : Age ≥35 and ≤50 years at screening (subjects with DS with age ≥35 and ≤39 years may be considered on the condition that there is prior evidence of amyloid results compatible with AD pathology at PET-scan and/or in biofluids).
11. Part 2 : Male or female subjects with DS with a cytogenetic diagnosis being either trisomy 21 or complete unbalanced translocation of the chromosome 21.
12. Part 2 : PET scan at screening consistent with the presence of amyloid pathology.
13. Part 2 : Subjects, their legal representatives (if applicable) and/or their study partners, in the opinion of the investigator, are able to understand the details of the study and to provide written informed consent before starting any study-related activities.
14. Part 2 : In the opinion of the investigator, subjects, their legal representatives (if applicable), and/or their study partners or informants are able to fully participate in the study, are sufficiently proficient in the official languages(s) of the country they are living in, and are capable of reliably completing study assessments.
15. Part 2 : Females who are either post-menopausal for at least 1 year and/or surgically sterilized, or females of childbearing potential or not post-menopausal 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 their participation. 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.
16. Part 2 : Mild to moderate intellectual disability as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification.
17. Part 2 : Subjects must have a study partner who has direct and regular contact, at least 10 hours per week, with the subject and who is able to provide reliable answers to questions related to the subject, according to the study investigator.

Exclusion criteria 20

1. Part 1 and Part 2 - Comorbidities: Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of the study vaccine (eg, moderate and/or severe untreated obstructive sleep apnea, clinically significant reduction in serum B12 or folate levels, clinically significant abnormalities of thyroid function, stroke, or other cerebrovascular conditions), as per investigator’s judgement.
2. Part 1 and Part 2 - Comorbidities: Subjects considered to be unable to be compliant with study-related activities (eg, completion of any study exams and assessments, respect of visit schedule and/or treatment administration) and/or to have comorbidities preventing the completion of any study exams and assessments (eg, significant hearing or visual impairments or other disabilities) according to the investigator.
3. Part 1 and Part 2 - Comorbidities: DSM-5 criteria for drug or alcohol abuse or dependence currently met within the past 5 years.
4. Part 1 and Part 2 - Comorbidities: History or presence of uncontrolled seizures. If history of seizures, they must be well controlled with no occurrence of seizures in the 2 years before study screening. The use of antiepileptic medications is permitted.
5. Part 1 and Part 2 - Comorbidities: Clinically significant arrhythmias or other clinically significant abnormalities on ECG at screening.
6. Part 1 and Part 2 - Comorbidities: Myocardial infarction within 1 year prior to baseline, unstable angina pectoris, or significant coronary artery disease.
7. Part 1 and Part 2 - Comorbidities: Concomitant or past history psychiatric or neurologic disorder other than those considered to be related to AD (eg, head injury with loss of consciousness, symptomatic stroke, Parkinson’s disease, severe carotid occlusive disease, transient ischemic attacks [TIAs], hemorrhagic and/or non-hemorrhagic stroke).
8. Part 1 and Part 2 - Comorbidities: History of meningitis or meningoencephalitis
9. Part 1 and Part 2 - Comorbidities: History of moderate or severe traumatic brain injury.
10. Part 1 and Part 2 - Comorbidities: History or presence of inflammatory neurological disorders including but not limited to neuromyelitis optica spectrum disorder (NMOSD).
11. Part 1 and Part 2 - Comorbidities: History of cancer within the past 5 years other than treated squamous cell carcinoma, basal cell carcinoma and melanoma in-situ, in-situ prostate cancer, or in-situ breast cancer which have been fully removed and are considered cured.
12. Part 1 and Part 2 - Comorbidities: History of chronic or recurrent infections judged to be clinically significant by the investigator and which would potentially hamper the evaluation of efficacy and safety assessments.
13. Part 1 and Part 2 - Comorbidities: History or presence of immunological or autoimmune disorders including but not limited to myasthenia gravis, systemic lupus erythematosus, Sjogren syndrome, and sarcoidosis.
14. Part 1 and Part 2 - Comorbidities: History of severe allergic reaction (eg, anaphylaxis) including, but not limited to severe allergic reaction to previous vaccines, foods, and/or medications.
15. Part 1 and Part 2 - Comorbidities: Clinically significant abnormal vital signs including sustained sitting blood pressure >160/90 mm Hg.
16. Part 1 and Part 2 - Comorbidities: Significant risk of suicide, defined using the C-SSRS as the subject answering “yes” to suicidal ideation questions 4 or 5 or answering “yes” to suicidal behavior within the past 12 months.
17. Part 1 and Part 2 - Comorbidities: Clinically significant infections or major surgical operation within 3 months prior to screening.
18. Part 1 and Part 2 - Comorbidities: Planned surgery anticipated to occur during participation in the study must be reviewed and approved by the medical monitor at screening.
19. Part 1 and Part 2 - Comorbidities: Subjects who have donated blood or blood products in the 30 days before screening or who plan to donate blood while participating in the study.
20. Part 1 and Part 2 - Comorbidities: Subjects with clinically uncontrolled diabetes mellitus and/or with hemoglobin A1c levels of ≥8.0 %.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and Tolerability: Adverse events (AEs); physical and neurological examination results; global assessment of tolerability; vital signs; brain MRI assessment; electrocardiogram (ECG); routine hematology and biochemistry evaluation in blood and urine; inflammatory and autoimmune markers in blood and CSF; suicidality as measured with Columbia-Suicide Severity Rating Scale (C-SSRS).

Secondary endpoints 1

1. Pharmacodynamic (Immunogenicity): Anti-Aβ antibody titers in serum (eg, geometric mean of antibody titers, change from baseline, responder rate, peak, and area under the curve [AUC]).

Investigational products

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

Test 1

Placebo 1

Auxiliary 2

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 9

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 87 files

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

Application history

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