Tau targeted vaccines in patients with early Alzheimer’s Disease

• Research type

  Research Study

• Full title

  A Phase Ib/IIa Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Immunogenicity of Different Doses, Regimens and Combinations of Tau Targeted Vaccines in Subjects with Early Alzheimer’s Disease

• IRAS ID

  261176

• Contact name

  Craig Ritchie

• Contact email

  craig.ritchie@ed.ac.uk

• Sponsor organisation

  AC Immune SA

• Eudract number

  2018-004573-27

• Clinicaltrials.gov Identifier

  NCT04445831

• Duration of Study in the UK

  3 years, 4 months, 24 days

• Research summary

  Summary of Research
  Alzheimer's disease (AD) is the most common cause of dementia. AD is a progressive condition, which means that it will continue to worsen as it develops. Symptoms include memory loss, personality and behavioural changes and loss of control over bodily functions. Occurrence is set to increase markedly over the coming decades due to ageing of the population. There is, therefore, clearly a major need for new approaches targeting the essential pathology of the disease and thereby slowing or halting its progression.

  The purpose of this research study is to evaluate the safety and effects on the body of the study vaccine, ACI-35.030 in patients with early AD who are aged between 50 and 75 years old. The study vaccine has been designed to stimulate the body’s immune system to make proteins called antibodies. These antibodies should remove an abnormal form of the Tau protein which accumulates in the brain in Alzheimer’s disease. It is hoped that the reduction of the build-up of the abnormal Tau proteins will slow down the progression of the disease. The study vaccine will be administered 4 times by an injection at the study site.

  The study is planned to involve approximately 32 people who have early AD at 15 sites worldwide. The study will involve 14 visits to the study site and 4 phone calls. Participation is expected to last 78 weeks. Participants will undergo general assessments at study visits including blood tests and neurological examinations. At some visits, participants will have MRI scans, electrocardiogram (ECG), lumbar puncture, tests of cognition, daily living function and behaviour. Participants will be asked to record changes to health and medication use in a diary. Participants will be supported by a caregiver/study partner during the study.

  Summary of Results
  ACI-35-1802: LAY SUMMARY OF STUDY RESULTS

  Study Title: A Phase Ib/IIa Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Immunogenicity of Different Doses, Regimens and Combinations of Tau Targeted Vaccines in Subjects with Early Alzheimer’s Disease

  Study No ACI-35-1802
  EudraCT: 2018-004573-27
  Sponsor: AC Immune SA,
  EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland

  About The Study
  Two investigational therapeutic vaccines named ACI-35.030 and JACI-35.054 were studied in people with early Alzheimer’s disease. These vaccines are called investigational because they are still being tested and are not on the market.

  A build-up of abnormal forms of a protein called tau in the brain is thought to play an important role in reduced mental function (cognitive decline) in people with Alzheimer’s disease (AD). ACI-35.030 and JACI-35.054 are designed to help the immune system produce so-called antibodies against abnormal tau. These antibodies should reduce the level of abnormal forms of tau and stop them from spreading between different parts of the brain. It is hoped that this will prevent or slow cognitive decline.

  This study mainly tested
  - whether the investigational vaccines are safe and tolerable for subjects with early AD,
  - the levels of antibodies produced in the blood against tau proteins after receiving the investigational vaccines at different dose levels.

  Some of responses being tested were called “exploratory” because the study was too small to be able to reliably detect effects on these tests. These “exploratory“ measures included effects on substances in the blood and other body fluids related to Alzheimer’s disease and effects on thinking, behaviour and daily living activities.

  Study Design and Conduct
  To take part, subjects had to be aged 50-75 years old and have early Alzheimer’s disease.

  A total of 79 subjects were screened for suitability to take part, of whom 57 subjects went on to take one of the investigational vaccines or placebo – in all, 31 received ACI-35.030, 12 received JACI-35.054 and 14 received placebo.

  Among the 57 people taking part, subjects were chosen at random to receive either ACI-35.030, JACI-35.054 or placebo and were to receive 4 injections over 48 weeks at weeks 0, 8, 24, and 48. After this they were followed up to week 74.

  This study was conducted in a total of 9 study sites in 4 countries (Finland, Sweden, the Netherland and the United Kingdom (UK)), after being approved by the responsible Authorities and Ethics Committees. The first subject entered the study on 31 July 2019 and the last study visit was on 05 September 2023.

  Results
  Of the 41 subjects in the cohort 1 (group receiving ACI-35.030 or placebo) there were 21 males and 20 females, with an average age of 67.1 years. In the cohort 2 (group receiving JACI-35.054 or placebo) there were 6 males and 10 females, with an average age of 65.6 years.

  Overall, the investigational medications were safe and well tolerated by the participating subjects. No subjects dropped out due to unwanted effects of the investigational vaccines.

  The commonest unwanted events (those in at least one in five people) reported in the ACI-35.030 active treatment group of cohort 1 were reactions at the site where the vaccine was injected, COVID 19 infection and fatigue, headache and nasopharyngitis (symptoms of a cold). The commonest unwanted effects (those in at least one in five people) reported in the group receiving JACI-35.054 were headache, injection site reaction, malaise, pyrexia (fever), epistaxis (nose bleed), myalgia, and ventricular extrasystoles (extra heart beats).

  Both ACI-35.030 and JACI-35.054 caused a clear response by the immune system to produce antibodies against abnormal tau forms, with the profile of ACI-35.030 being especially promising. Larger studies will be needed to investigate possible effects on substances in the blood linked to Alzheimer’s disease.

  Next steps
  Based on these promising results, the ACI-35.030 vaccine has been chosen for further testing.

• REC name

  West of Scotland REC 1

• REC reference

  19/WS/0056

• Date of REC Opinion

  19 Jun 2019

• REC opinion

  Further Information Favourable Opinion