ACI-24-1801 - Phase 2 study of ACI-24 versus placebo in AD patients
Research type
Research Study
Full title
A Phase II Double-Blind, Randomized, Placebo-Controlled, Adaptive Design Study to Assess the Safety, Tolerability, Immunogenicity and Target Engagement of ACI-24 Formulations in Patients with Mild Alzheimer’s Disease
IRAS ID
246134
Contact name
Julien Rongere
Contact email
Sponsor organisation
AC Immune SA
Eudract number
2018-000445-39
Clinicaltrials.gov Identifier
18/WM/0212, REC initial submission (West Midlands - Coventry & Warwickshire REC)
Duration of Study in the UK
3 years, 3 months, 31 days
Research summary
Summary of Research
The study tests the safety, tolerability, and immune response to ACI-24, a vaccine against beta-amyloid, a protein involved in the pathology of Alzheimer´s disease. ACI-24 is a vaccine which works by stimulating the production of antibodies against beta amyloid to reduce the level of the protein in the brain and prevent its buildup. The vaccine has been designed to avoid the unwanted inflammation in the brain seen in 6 per cent of subjects with an earlier vaccine from another company. The vaccine has been given to 36 participants with Alzheimer´s disease and 12 with Down´s syndrome and has been well tolerated and safe to date. Initially 18 subjects with mild Alzheimer´s disease will receive either the active vaccine (12 subjects) or placebo (6 subjects) for up to 18 months, with regular assessments of safety, immunogenicity and effects on biomarkers including amyloid PET scans. The sample will be expanded to 45 subjects if an adequate response is observed after 6 months. To increase the immune response the current study looks at the safety and effects of the vaccine given intramuscularly. Other formulations of the vaccine will be tested as they become available to select the optimal version of the vaccine for larger studies.Summary of Results
CLINICAL STUDY REPORT LAY SUMMARY
Study Title: A Phase 2 Double-Blind, Randomized, Placebo-Controlled, Adaptive Design Study to Assess the Safety, Tolerability, Immunogenicity and Target Engagement of ACI-24 Formulations in Patients with Mild Alzheimer’s Disease
EudraCT: 2018-000445-39Sponsor: AC Immune SA,
EPFL Innovation Park, Building B, 1015 Lausanne, SwitzerlandAbout The Study
Alzheimer’s disease (AD) is a disorder of insidious onset. Patients suffering from AD loose memory and other cognitive functions. This results in losing the ability to perform daily living activities and concluding the autonomy of the patients.
An investigational medication named ACI-24 was tested for the treatment of mild Alzheimer’s disease. ACI-24 is an investigational vaccine because its safety, effectiveness, and how it works are still being studied.
A build-up of the protein Abeta (Aβ) in the brain is thought to play an important role in reduced mental function (cognitive decline) in people with Alzheimer’s disease. ACI 24 is designed to help the immune system produce antibodies against Aβ. These antibodies should reduce the amount of Aβ in the brain and may slow cognitive decline.
This study mainly tried to
- assess if the investigational vaccine ACI-24 is safe and tolerable for subjects with mild AD,
- assess the effects of ACI-24 formulations on the induction of anti-amyloid beta (anti-Aβ) antibody responses in blood of participating subjects,
- assess the effects of ACI-24 formulations on brain amyloid load in subjects with mild AD, assessed by florbetaben-positron emission tomography (PET), a method to make these changes of amyloid in subjects visible and measurable.Furthermore, the study aimed to
- explore the effects of ACI-24 formulations on putative biomarkers, as signs of the progression
of AD including concentrations of AD marker in blood and/or cerebrospinal fluid (CSF - body fluid that surrounds the spinal cord),
- explore the effects of ACI-24 formulations on specific cells involved in the antibody response measured in blood of participants,
- explore the effects of ACI-24 formulations on whole brain volume and volumes of specific brain areas measured with MRI (magnetic resonance imaging) method,
- explore the effects of ACI-24 formulations on clinical and cognitive symptoms in subjects with mild AD,
- explore the influence of ACI-24 formulations on inflammatory markers in blood.Treatment Being Studied
For this study, the treatment studied was an investigational vaccine (ie one not yet on the market) known as ACI-24. Study participants received either ACI-24 or placebo (which looks the same as ACI-24 but does not contain any active ingredients). By chance 2 of 3 subjects received ACI-24 whereas 1 of 3 subjects received placebo. ACI-24 or placebo were be injected into the study participant’s arm muscle (in some cases it may be injected into the thigh).
Study Design
This study was conducted in a total of 11 active study sites in 4 countries (2 sites in Finland, 1 site in Sweden, 7 sites in the United Kingdom (UK), and 1 site in Poland) after being approved by the responsible Authorities and Ethics Committees.
21 subjects participated in the trial. All subjects agreed to participate by signing an Informed Consent Form after being informed in detail by the responsible investigator about study procedures, potential risks and benefits of the study participation. All subjects had the right to withdraw formal consent without prejudice at any time during the study.
The participants received either ACI-24 or placebo via up to 8 intramuscular injections over 18 months. After this treatment period, the participants were followed-up for 6 months because of safety reasons.
Results
10 male and 11 female patients participated in the trial. At the time of study participation, they were between 58 and 85 years old. The mean age was approx. 71 years. 95% of the patients were white, 5% Asian.Overall, the investigational medication was safe and well tolerated by the participating subjects.
Local tolerability was also good, mild injection site pain was reported on two occasions in 1 subject receiving ACI-24.ACI-24 induced antibodies against anti-amyloid beta (anti-Aβ) No apparent changes were seen in the level of amyloid on PET scans compared to placebo in this limited study population. The level of beta-amyloid proteins in the cerebrospinal fluid was increased after ACI-24 suggesting that the vaccine was having an effect on its target. Memory assessments and tests of function did not show differences from placebo, but the study was known to be too small to be able to detect such changes with this type of agent.
Overall, the results of the study were promising and supported further investigation of the ACI-24 using an optimized formulation to improve the antibody response.
Next steps and further researchAn optimized formulation of ACI-24 has been developed to increase the immune response, and will be studied in subjects with AD and Down syndrome.
Where can I learn more about this study?More in information is available when entering the EudraCT number below in the EU Trial Register webpage: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agba4yu73OCS9U-2BkKS40W1kfatiYvtk1-2B2gi1K6vKImual7ko-2F6fv-2B6wOlLZweXjcozGbmfnK-2BfC-2F-2FpWkHWIHEwKc-3DKRhR_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YL9ER58WEKrE-2Fs0l2NxDA-2Btx7FM8BnUH9dbhQrRy3gN2gc5es3dyW-2Bwmz3-2FO5yHr515IurXGTWsO1AzMTuOss-2FMlBlV88Ie4ZcFCJAqAJD6b7S-2F23YBEv3qhTzXmGAFPJz-2FIJrsJh-2B24cgh8I5OG8-2Frs3Gi008aV-2FmAbvg8hv4aog-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Ccd06a74b19a746f016b608da23b66583%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637861563542243868%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=ZU%2FWvO1OM67POgSbt6N8tUlWBo4%2FI9jO3smRcRiZQI0%3D&reserved=0
EudraCT Number: 2018-000445-39REC name
South Central - Oxford C Research Ethics Committee
REC reference
18/SC/0502
Date of REC Opinion
8 Oct 2018
REC opinion
Favourable Opinion