A Study to Evaluate the Safety, Tolerability and Immunogenicity of Tau Targeted Vaccines in Participants With Early Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT04445831
• Recruitment Status: Active, not recruiting
• First Posted: June 24, 2020
• Last Update Posted: June 27, 2022
• Sponsor: AC Immune SA
• Collaborator: Janssen Research & Development, LLC
• Information provided by (Responsible Party): AC Immune SA

Study Description

Brief Summary:

This study is a 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 participants with early Alzheimer's Disease.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease; Cognitive Impairment; Tauopathies; Mild Cognitive Impairment; Dementia; Brain Diseases; Central Nervous System Diseases	Biological: ACI-35.030; Other: Placebo; Biological: JACI-35.054	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: July 31, 2019
• Estimated Primary Completion Date: October 31, 2023
• Estimated Study Completion Date: October 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo administered at predefined time points over a 48-week period.	Other: Placebo; Administration of Placebo
Experimental: ACI-35.030 - Low dose; Active vaccine administered at predefined time points over a 48-week period.	Biological: ACI-35.030; Administration of a Low dose of ACI-35.030
Experimental: ACI-35.030 - Medium dose; Active vaccine administered at predefined time points over a 48-week period.	Biological: ACI-35.030; Administration of a Medium dose of ACI-35.030
Experimental: ACI-35.030 - High dose; Active vaccine administered at predefined time points over a 48-week period.	Biological: ACI-35.030; Administration of a High dose of ACI-35.030
Experimental: JACI-35.054 - Low dose; Active vaccine administered at predefined time points over a 48-week period.	Biological: JACI-35.054; Administration of a Low dose of JACI-35.054
Experimental: JACI-35.054 - Medium dose; Active vaccine administered at predefined time points over a 48-week period.	Biological: JACI-35.054; Administration of a Medium dose of JACI-35.054

Outcome Measures

Primary Outcome Measures :

1. Number of participants with Adverse Events (AEs) assessed by intensity (mild, moderate or severe) and causal relationship (unrelated, unlikely, possibly or probably related) [ Time Frame: from screening up to week 74 ]
2. Change from baseline in anti-phosphorylated Tau IgG titers in blood [ Time Frame: from baseline up to week 74 ]
3. Mean change from baseline in systolic and diastolic blood pressure (mmHg) [ Time Frame: from baseline up to week 74 ]
4. Mean change from baseline in heart rate (bpm) [ Time Frame: from baseline up to week 74 ]
5. Mean change from baseline in body temperature (degree Celsius) [ Time Frame: from baseline up to week 74 ]
6. Number of participants reporting suicidal ideation or behavior using Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: from baseline up to week 74 ]
7. Number of participants with abnormal MRI results [ Time Frame: from baseline up to week 74 ]

Secondary Outcome Measures :

1. Change from baseline in anti-Tau IgG titers in blood [ Time Frame: from baseline up to week 74 ]
2. Change from baseline in anti-phosphorylated Tau IgM titers in blood [ Time Frame: from baseline up to week 74 ]
3. Change from baseline in anti-Tau IgM titers in blood [ Time Frame: from baseline up to week 74 ]

Other Outcome Measures:

1. Change from baseline of functional performance using Clinical Dementia Rating scale Sum of Boxes (CDR-SB) [ Time Frame: from baseline up to week 74 ]
   The score ranges from 0 to 18. A higher score indicates a worse outcome.
2. Change from baseline of cognitive performance using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: from baseline up to week 74 ]
   The total scale index score ranges from 40 to 160. A higher score indicates a better outcome.
3. Change from baseline of behavior using Neuropsychiatric Inventory Scale (NPI) [ Time Frame: from baseline up to week 74 ]
   The score ranges from 0 to 144. A higher score indicates a worse outcome.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female with age from 50 and up to 75 years old inclusive.
2. Mild Cognitive Impairment (MCI) due to AD or Mild AD according to NIA-AA criteria and Clinical Dementia Rating scale (CDR) global score of 0.5 or 1 respectively.
3. Mini Mental State Examination (MMSE) score of 22 or above.
4. Abnormal level of CSF Abeta amyloid 42 (Aß42) consistent with AD pathology at screening.
5. Subjects either not taking any marketed treatment for AD or receiving a stable dose of an acetylcholinesterase inhibitor and/or memantine for at least 3 months prior to baseline.
6. Subjects cared for by a reliable informant or caregiver to assure compliance, assist with clinical assessments and report safety issues.
7. Women must be post-menopausal for at least one year and/or surgically sterilized.
8. Subjects who in the opinion of the investigator is able to understand and provide written informed consent.
9. Both subject and informant or caregiver must be fluent in one of the languages of the study and able to comply with all study procedures, including lumbar punctures.

Exclusion criteria:

1. Participation in previous clinical trials for AD and/or for neurological disorders using active immunization unless there is documented evidence that the subject was treated with placebo only and the placebo vaccine is not expected to induce any specific immune response.
2. Participation in previous clinical trials for AD and/or for neurological disorders using any passive immunization within the past 6 months (or 5 half-lives of the investigational antibody, whichever is longer) prior to screening unless there is documented evidence that the subject was treated with placebo only and the placebo is not expected to induce any specific immune response.
3. Participation in previous clinical trials for AD and/or for neurological disorders using any small molecule drug including BACE-1 inhibitors within the past 3 months prior to screening.
4. Concomitant participation in any other clinical trial using experimental or approved medications or therapies.
5. Presence of positive Anti-nuclear Antibody (ANA) titers at a dilution of at least 1:160 in subjects without clinical symptoms of auto-immune disease.
6. Current or past history of auto-immune disease, or clinical symptoms consistent with the presence of auto-immune disease.
7. Immune suppression including but not limited to the use of immunosuppressive drugs or systemic steroids unless they have been prescribed transiently more than 3 months prior to screening.
8. History of severe allergic reaction (e.g., anaphylaxis) including but not limited to severe allergic reaction to previous vaccines and/or medications.
9. Prior history of clinically significant hypoglycaemic episodes.
10. Drug or alcohol abuse or dependence currently met or within the past five years according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria.
11. Any clinically significant medical condition likely to interfere with the evaluation of safety and tolerability of the study treatment and/or the adherence to the full study visit schedule.
12. Any clinically significant medical condition likely to impact the immune system (e.g, any history of acquired or innate immune system disorder).
13. Use of hydralazine, procainamide, quinidine, isoniazide, TNF-inhibitors, minocycline within the last 12 months prior to screening.
14. Use of diltiazem unless on a stable dose for at least 3 months prior to screening.
15. Significant risk of suicide defined, using the Columbia-Suicide Severity Rating Scale, as the subject answering: "yes" to suicidal ideation questions 4 or 5 or answering: "yes" to suicidal behavior within the past 12 months.
16. Concomitant psychiatric or neurologic disorder other than those considered to be related to AD.
17. History or presence of uncontrolled seizures.
18. History of meningoencephalitis within the past 10 years prior to screening.
19. Subjects with a history of hemorrhagic and/or non-hemorrhagic stroke.
20. Presence or history of peripheral neuropathy.
21. History of inflammatory neurological disorders with potential for CNS involvement.
22. Screening MRI scan showing structural evidence of alternative pathology not consistent with AD which could cause the subject's symptoms.
23. MRI examination cannot be done for any reason, including but not limited to metal implants contraindicated for MRI studies and/or severe claustrophobia.
24. Significant hearing or visual impairment or other issues judged relevant by the investigator preventing to comply with the protocol and to perform the outcome measures.
25. Clinically significant infections or major surgical operation within 3 months prior to screening.
26. Any vaccine received within the past 2 weeks before screening, including influenza vaccine.
27. Clinically significant arrhythmias or other clinically significant abnormalities on ECG at screening.
28. Myocardial infarction within one year prior to baseline, unstable angina pectoris, or significant coronary artery disease.
29. History of cancer within the past 5 years other than treated squamous cell carcinoma, basal cell carcinoma and melanoma in situ, or in-situ prostate cancer or in-situ breast cancer which have been fully removed and are considered cured.
30. Clinically significant deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, that are judged to be clinically significant in the opinion of the investigator.
31. Pregnancy confirmed by blood test at screening, or subject planning to be pregnant or lactating.
32. Receipt of any anticoagulant drug or antiplatelet drug, except aspirin at doses of 100 mg daily or lower.
33. Receipt of any antipsychotic drugs unless on stable low doses for the treatment of insomnia.
34. Donation of blood or blood products within 30 days prior to screening or plans to donate blood while participating in the study.
35. Positive Venereal Disease Research Laboratory (VDRL) consistent with active syphilis at screening.
36. Positive HIV test at screening.
37. Laboratory or clinical evidence of active hepatitis B and/or C at screening.
38. Serum creatinine greater than 1.5x upper limit of normal, abnormal thyroid function tests or clinically significant reduction in serum B12 or folate levels.

Contacts and Locations

Locations

Finland

Clinical Research Services Helsinki

Helsinki, Finland

Itä-Suomen Yliopisto - Kuopion Kampus

Kuopio, Finland

Clinical Research Services Turku

Turku, Finland

Netherlands

Brain Research Center - Den Bosch

's-Hertogenbosch, Netherlands

Brain Research Center - Amsterdam

Amsterdam, Netherlands

Sweden

Minnesmottagningen - Sahlgrenska Universitetssjukhuset - Mölndal Sjukhus

Mölndal, Sweden

Kognitiv Mottagning - Karolinska Universitetssjukhuset - Huddinge

Stockholm, Sweden

United Kingdom

Edinburgh Clinical Research Facility

Edinburgh, United Kingdom

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Sponsors and Collaborators

AC Immune SA

Janssen Research & Development, LLC

Investigators

• Principal Investigator: Philip Scheltens, MD; Amsterdam UMC Alzheimer Center de Boelelaan Amsterdam The Netherlands

More Information

• Responsible Party: AC Immune SA
• ClinicalTrials.gov Identifier: NCT04445831
• Other Study ID Numbers: ACI-35-1802; 2018-004573-27 ( EudraCT Number )
• First Posted: June 24, 2020
• Last Update Posted: June 27, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AC Immune SA:

Alzheimer's Disease; Cognitive Impairment; Tauopathies; Mild Cognitive Impairment; Dementia; Brain Diseases; Central Nervous System Diseases

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases; Tauopathies; Cognitive Dysfunction; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders