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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04445831
Recruitment Status : Recruiting
First Posted : June 24, 2020
Last Update Posted : June 24, 2020
Sponsor:
Collaborator:
Janssen Research and Development LLC
Information provided by (Responsible Party):
AC Immune SA

Tracking Information
First Submitted Date  ICMJE June 22, 2020
First Posted Date  ICMJE June 24, 2020
Last Update Posted Date June 24, 2020
Actual Study Start Date  ICMJE July 31, 2019
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2020)
  • 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 ]
  • Change from baseline in anti-phosphorylated Tau IgG titers in blood [ Time Frame: from baseline up to week 74 ]
  • Mean change from baseline in systolic and diastolic blood pressure (mmHg) [ Time Frame: from baseline up to week 74 ]
  • Mean change from baseline in heart rate (bpm) [ Time Frame: from baseline up to week 74 ]
  • Mean change from baseline in body temperature (degree Celsius) [ Time Frame: from baseline up to week 74 ]
  • Number of participants reporting suicidal ideation or behavior using Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: from baseline up to week 74 ]
  • Number of participants with abnormal MRI results [ Time Frame: from baseline up to week 74 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2020)
  • Change from baseline in anti-Tau IgG titers in blood [ Time Frame: from baseline up to week 74 ]
  • Change from baseline in anti-phosphorylated Tau IgM titers in blood [ Time Frame: from baseline up to week 74 ]
  • Change from baseline in anti-Tau IgM titers in blood [ Time Frame: from baseline up to week 74 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 22, 2020)
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety, Tolerability and Immunogenicity of Tau Targeted Vaccines in Participants With Early Alzheimer's Disease
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Alzheimer's Disease
  • Cognitive Impairment
  • Tauopathies
  • Mild Cognitive Impairment
  • Dementia
  • Brain Diseases
  • Central Nervous System Diseases
Intervention  ICMJE
  • Biological: ACI-35.030
    Administration of a Low dose of ACI-35.030
  • Biological: ACI-35.030
    Administration of a Medium dose of ACI-35.030
  • Biological: ACI-35.030
    Administration of a High dose of ACI-35.030 (optional)
  • Other: Placebo
    Administration of Placebo
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo administered at predefined time points over a 48-week period.
    Intervention: Other: Placebo
  • Experimental: ACI-35.030 - Low dose
    Active vaccine administered at predefined time points over a 48-week period.
    Intervention: Biological: ACI-35.030
  • Experimental: ACI-35.030 - Medium dose
    Active vaccine administered at predefined time points over a 48-week period.
    Intervention: Biological: ACI-35.030
  • Experimental: ACI-35.030 - High dose
    Active vaccine administered at predefined time points over a 48-week period (optional).
    Intervention: Biological: ACI-35.030
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 22, 2020)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2023
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female with age from 50 and up to 75 years old inclusive.
  2. Mild AD or Mild Cognitive Impairment (MCI) due to AD according to NIA-AA criteria.
  3. Mini Mental State Examination (MMSE) score of 22 or above.
  4. Levels of CSF Amyloid Beta 42 (Aß42) and phosphorylated Tau at screening consistent with NIA-AA 2018 criteria for AD pathology.
  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 12 months prior to screening.
  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 except at 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Olivier Sol, MD +41 21 345 9121 clinicaltrials@acimmune.com
Contact: Benedicte Le +41 21 345 9121 clinicaltrials@acimmune.com
Listed Location Countries  ICMJE Finland,   Netherlands,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04445831
Other Study ID Numbers  ICMJE ACI-35-1802
2018-004573-27 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party AC Immune SA
Study Sponsor  ICMJE AC Immune SA
Collaborators  ICMJE Janssen Research and Development LLC
Investigators  ICMJE
Principal Investigator: Philip Scheltens, MD Amsterdam UMC Alzheimer Center de Boelelaan Amsterdam The Netherlands
PRS Account AC Immune SA
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP