A Trial to Evaluate the Effects of BCG in Adults With MCI and Mild-to-Moderate AD

NCT05004688 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 2021P002577
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

A study of the effects of Bacillus Calmette-Guérin (BCG) immunization on cerebrospinal fluid and blood-based biomarkers in older with mild cognitive impairment and mild-to-moderate to Alzheimer's disease.

Conditions

Mild Cognitive Impairment; Mild Dementia; Moderate Dementia; Alzheimer Disease

Outcome Measures

Primary Outcomes (14)

• Blood Biomarkers of Pharmacodynamic Response- Cytokines

  Change in concentration (Average difference) of circulating cytokines in blood from baseline (Average difference).Cytokines include: Plasma IFN-g (pg/ml), Plasma IL-1b (pg/ml), Plasma IL-2 (pg/ml), Plasma IL-6 (pg/ml), Plasma IL-10 (pg/ml), Plasma TNF-a (pg/ml). Mean differences (and standard deviations) from baseline values are presented for the Day 364 (end of study) sample collections for the 4 participants in the study.

  Baseline to Day 364

• CSF Biomarkers of Pharmacodynamic Response- Cytokines

  Change in concentration (Average difference) of circulating cytokines in CSF from baseline (Average difference). Cytokines measured include: CSF IFN-g (pg/ml), CSF IL-1b (pg/ml), CSF IL-2 (pg/ml), CSF IL-6 (pg/ml), CSF IL-10 (pg/ml), CSF TNF-a (pg/ml). Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 7 participants with complete data in the study.

  Baseline to Day 84

• CSF Biomarkers of Pharmacodynamic Response- Cytokines

  Change in concentration (Average Difference) of circulating cytokines in CSF from baseline. Cytokines measured include: CSF IFN-g (pg/ml), CSF IL-1b (pg/ml), CSF IL-2 (pg/ml), CSF IL-6 (pg/ml), CSF IL-10 (pg/ml), CSF TNF-a (pg/ml). Mean differences (and standard deviations) from baseline values are presented for the Day 364 (end of study) sample collections for the 4 participants with complete data in the study.

  Baseline to Day 364

• Blood Biomarkers of AD Pathology-ATN

  Change in concentration (Average difference) of ATN markers of AD pathophysiology phospho-tau (217 and 181) and neurofilament light protein biomarkers in blood from baseline. Mean differences (and standard deviations) from baseline values are presented for the Day 364 (end of study) sample collections for the 4 participants in the study at this timepoint.

  Baseline to Day 364

• CSF Biomarkers of AD Pathology-ATN

  Change in concentration (Average difference) of ATN markers of AD pathophysiology (phospho-tau181, total tau, and neurofilament light protein biomarkers in CSF from baseline. Mean differences (and standard deviations) from baseline values are presented Day 364 (end of study) sample collections for the 4 participants in the study at this timepoint.

  Baseline to Day 364

• Blood Biomarkers of AD Pathology-ATN

  Change in concentration (Average difference) of ATN markers of AD pathophysiology (phospho-tau (217 and 181) and neurofilament light protein biomarkers in blood from baseline. Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 7 participants in the study at this timepoint.

  Baseline to Day 84

• CSF Biomarkers of AD Pathology-ATN

  Change in concentration (Average difference) of ATN markers of AD pathophysiology (phospho-tau181, total tau, and neurofilament light protein biomarkers in CSF from baseline. Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 4 participants in the study at this timepoint.

  Baseline to Day 84

• Cognitive Measures (RBANS)

  Change in Total Scale Index (TSI) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Mean differences and standard deviations are expressed for the difference between the Day 84 TSI and the baseline TSI for the 7 participants in the study. The RBANS is an assessment commonly used in clinical trials to assess cognitive functioning. Scores range from 40 to 160 with lower scores indicating poorer performance, thus a score decrease would indicate a decrease in cognitive performance. A score under 78 is typically indicative of cognitive impairment.

  Baseline to Day 84

• Cognitive Measures (RBANS)

  Change in Total Scale Index (TSI) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Mean differences and standard deviations are expressed for the difference between the end of study TSI and the baseline TSI for the 4 participants in the study. The RBANS is an assessment commonly used in clinical trials to assess cognitive functioning. Scores range from 40 to 160 with lower scores indicating poorer performance, thus a score decrease would indicate a decrease in cognitive performance. A score under 78 is typically indicative of cognitive impairment.

  Baseline to Day 364

• Amyloid-β42/40 Average Difference in Blood

  Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40 ratio) in blood from baseline.

  Baseline to Day 364

• Amyloid-β42/40 Average Difference in CSF

  Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline.

  Baseline to Day 364

• Amyloid-β42/40 Average Difference in Blood - Baseline to Day 84

  Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in blood from baseline.

  Baseline to Day 84

• Amyloid-β42/40 Average Difference in CSF - Baseline to Day 84

  Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline.

  Baseline to Day 84

• Blood Biomarkers of Pharmacodynamic Response - Cytokines

  Change in concentration of circulating cytokines in blood plasma from baseline. Cytokines include: Plasma IFN-g (pg/ml), Plasma IL-1b (pg/ml), Plasma IL-2 (pg/ml), Plasma IL-6 (pg/ml), Plasma IL-10 (pg/ml), Plasma TNF-a (pg/ml). Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 7 participants in the study at that time.

  Baseline to Day 84

Study Arms (1)

BCG

EXPERIMENTAL

Active BCG immunization

Biological: Biological/Vaccine: Bacillus Calmette-Guerin (BCG)

Interventions

Biological/Vaccine: Bacillus Calmette-Guerin (BCG) BIOLOGICAL

Two Bacillus Calmette-Guérin (Japan BCG) vaccine injections spaced four week apart. Each injection will have 0.36-3.9 x 10\^6 colony forming units (CFU) reconstituted in 0.1 mL saline.

Also known as: BCG

BCG

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals between the ages of 55-85;
• MCI or moderate dementia due to AD as defined by the 2011 NIA-AA Workgroup recommendations;
• MoCA ≥ 8 at screening;
• Global CDR between 0.5-2 (inclusive) at screening;
• Amyloid and/or tau biomarkers indicative of AD pathology;
• Education level, English language skills and literacy indicates subject will be able to complete all assessments;
• Has a study partner who, in the investigator's judgement, has frequent, direct contact with the participant at least several days a week, can accompany the participant to all visits, and is also able to provide information to study investigator/staff;
• Willing and able to complete all assessment and study procedures, including blood and lumbar punctures, and clinical assessments;
• If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline;
• Negative test results for HIV antibody and Tuberculosis (QuantiFERON) at screening;
• No prior BCG exposure either through birth vaccinations (born in North American) or BCG bladder cancer treatment.

You may not qualify if:

• History of chronic infectious disease, such as HIV or untreated or active hepatitis;
• History of tuberculosis, positive interferon-gamma release assay (IGRA, also known as the QuantiFERON-TB test), including a test with a high reactivity to mycobacteria of non-tuberculosis variety;
• Prior BCG vaccination, positive T-spot tuberculosis test or a T-spot test showing significant Mycobacteria exposure;
• A positive SARS-CoV-2 PCR result within 3 months of screening, or known close contact with a confirmed COVID-19 positive person or symptoms highly suspicious for COVID-19 (per CDC guidelines) within 1 month of screening, including fever, cough, shortness of breath, chills, muscle pain, new loss of taste or smell, vomiting or diarrhea, and/or sore throat, based on clinician's judgment;
• History of treatment with metformin within the past one year;
• Treatment with other investigational agents which, at the discretion of the investigator, interfere with safety and/or study outcomes;
• Current treatment with immunosuppressants (calcineurin inhibitors, corticosteroids, or biological or cytotoxic immunosuppressants, or disease or condition likely to require high dose steroid or immunosuppressive therapy);
• Other conditions or treatments associated with increased risk of infections or treatment with immunosuppressive medications for any reason;
• Current treatment with aspirin \> 160 mg/day or chronic, daily NSAIDs;
• Current (as of time of study screening) or chronic use of antibiotics;
• History of keloid formation;
• Living with someone who is immunosuppressed and/or at high risk for infectious diseases (for example, HIV+ or taking immunosuppressive medications for any reason), or in a job (e.g. healthcare) in which the subject works with immunosuppressed populations;
• Other/confounding neurological or psychiatric condition, unstable medical or psychiatric conditions, contraindications to BCG use and lab abnormalities or concurrent medication use posing risk for BCG or study procedures;
• Laboratory abnormalities in B12, Folate, TSH, or other common laboratory parameters that may contribute to cognitive dysfunction per clinician judgment;
• Laboratory abnormalities in CBC, electrolytes, LFTs, BUN, Cr, total serum immunoglobulins, ESR, CRP, or urinalysis posing risk to treatment with BCG per clinician judgment;

Sponsors & Collaborators

• Steven E Arnold, MD: lead

Study Sites (1)

Alzheimer's Clinical and Translational Research Unit

Charlestown, Massachusetts, 02129, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Biological Products; BCG Vaccine

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Complex Mixtures; Tuberculosis Vaccines; Bacterial Vaccines; Vaccines

Results Point of Contact

• Title: Kayla McEachern
• Organization: Mass General

kmceachern2@mgh.harvard.edu

617 643 5265

Study Officials

• Steven Arnold, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: open-label

Study Record Dates

• First Submitted: August 6, 2021
• First Posted: August 13, 2021
• Study Start: March 25, 2022
• Primary Completion: January 15, 2024
• Study Completion: January 15, 2024
• Last Updated: April 13, 2025
• Results First Posted: April 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)