Trial Outcomes & Findings for A Trial to Evaluate the Effects of BCG in Adults With MCI and Mild-to-Moderate AD (NCT NCT05004688)
NCT ID: NCT05004688
Last Updated: 2025-04-13
Results Overview
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.
COMPLETED
PHASE2
15 participants
Baseline to Day 364
2025-04-13
Participant Flow
Participant milestones
| Measure |
Active BCG Immunization
Active BCG immunization
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Overall Study
STARTED
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15
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Overall Study
COMPLETED
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4
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Overall Study
NOT COMPLETED
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11
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Reasons for withdrawal
| Measure |
Active BCG Immunization
Active BCG immunization
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Overall Study
Protocol Violation
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7
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Overall Study
Physician Decision
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2
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Overall Study
Withdrawal by Subject
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2
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Baseline Characteristics
A Trial to Evaluate the Effects of BCG in Adults With MCI and Mild-to-Moderate AD
Baseline characteristics by cohort
| Measure |
Active BCG Immunization
n=15 Participants
Active BCG immunization
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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5 Participants
n=5 Participants
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Age, Categorical
>=65 years
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10 Participants
n=5 Participants
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Sex: Female, Male
Female
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9 Participants
n=5 Participants
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Sex: Female, Male
Male
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6 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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Race (NIH/OMB)
White
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15 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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CSF Collected
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7 Participants
n=5 Participants
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Blood Collected
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7 Participants
n=5 Participants
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Cognitive testing measured
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7 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline to Day 364Change 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.
Outcome measures
| Measure |
Active BCG Immunization
n=4 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Blood Biomarkers of Pharmacodynamic Response- Cytokines
Plasma IL-2 (pg/ml)
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20.309 picogram/milliliter (pg/ml)
Standard Deviation 19.205
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Blood Biomarkers of Pharmacodynamic Response- Cytokines
Plasma IL-6 (pg/ml)
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2293.879 picogram/milliliter (pg/ml)
Standard Deviation 4308.539
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Blood Biomarkers of Pharmacodynamic Response- Cytokines
Plasma IL-10 (pg/ml)
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366.090 picogram/milliliter (pg/ml)
Standard Deviation 656.157
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Blood Biomarkers of Pharmacodynamic Response- Cytokines
Plasma IFN-g (pg/ml)
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26.672 picogram/milliliter (pg/ml)
Standard Deviation 125.864
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Blood Biomarkers of Pharmacodynamic Response- Cytokines
Plasma IL-1b (pg/ml)
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190.829 picogram/milliliter (pg/ml)
Standard Deviation 181.329
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Blood Biomarkers of Pharmacodynamic Response- Cytokines
Plasma TNF-a (pg/ml)
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53.903 picogram/milliliter (pg/ml)
Standard Deviation 54.002
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PRIMARY outcome
Timeframe: Baseline to Day 84Population: Since this outcome was analyzing the average difference between Day 0 and Day 84, there were more participants enrolled for these times points than when comparing Day 0 to Day 364. 15 participants started the trial, and only 4 completed, thus there were 7 active participants for the Day 84 timepoint.
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.
Outcome measures
| Measure |
Active BCG Immunization
n=7 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IFN-g (pg/ml)
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0.053 picogram/milliliter (pg/ml)
Standard Deviation 13.002
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IL-1b (pg/ml)
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-1.287 picogram/milliliter (pg/ml)
Standard Deviation 15.192
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IL-2 (pg/ml)
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8.103 picogram/milliliter (pg/ml)
Standard Deviation 20.326
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IL-6 (pg/ml)
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21.009 picogram/milliliter (pg/ml)
Standard Deviation 1220.991
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IL-10 (pg/ml)
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-3.057 picogram/milliliter (pg/ml)
Standard Deviation 80.133
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF TNF-a (pg/ml)
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-0.396 picogram/milliliter (pg/ml)
Standard Deviation 11.426
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PRIMARY outcome
Timeframe: Baseline to Day 364Change 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.
Outcome measures
| Measure |
Active BCG Immunization
n=4 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IFN-g (pg/ml)
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-14.368 picogram/milliliter (pg/ml)
Standard Deviation 13.773
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IL-1b (pg/ml)
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5.510 picogram/milliliter (pg/ml)
Standard Deviation 10.867
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IL-2 (pg/ml)
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-12.910 picogram/milliliter (pg/ml)
Standard Deviation 22.841
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IL-6 (pg/ml)
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710.455 picogram/milliliter (pg/ml)
Standard Deviation 1827.730
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF IL-10 (pg/ml)
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-95.078 picogram/milliliter (pg/ml)
Standard Deviation 144.162
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CSF Biomarkers of Pharmacodynamic Response- Cytokines
CSF TNF-a (pg/ml)
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0.300 picogram/milliliter (pg/ml)
Standard Deviation 19.083
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PRIMARY outcome
Timeframe: Baseline to Day 364Change 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.
Outcome measures
| Measure |
Active BCG Immunization
n=4 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Blood Biomarkers of AD Pathology-ATN
Plasma pTau217 (pg/ml)
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-1.392 picogram/milliliter (pg/ml)
Standard Deviation 5.382
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Blood Biomarkers of AD Pathology-ATN
Plasma pTau181 (pg/ml)
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0.233 picogram/milliliter (pg/ml)
Standard Deviation 0.362
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Blood Biomarkers of AD Pathology-ATN
Plasma NfL (pg/ml)
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-1.852 picogram/milliliter (pg/ml)
Standard Deviation 5.810
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PRIMARY outcome
Timeframe: Baseline to Day 364Change 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.
Outcome measures
| Measure |
Active BCG Immunization
n=4 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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CSF Biomarkers of AD Pathology-ATN
CSF pTau181 (pg/ml)
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-5.955 picogram/milliliter (pg/ml)
Standard Deviation 10.135
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CSF Biomarkers of AD Pathology-ATN
CSF NfL (pg/ml)
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-55.413 picogram/milliliter (pg/ml)
Standard Deviation 477.315
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CSF Biomarkers of AD Pathology-ATN
CSF tTau (pg/ml)
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-3.595 picogram/milliliter (pg/ml)
Standard Deviation 26.970
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PRIMARY outcome
Timeframe: Baseline to Day 84Population: Since this outcome was analyzing the average difference between Day 0 and Day 84, there were more participants enrolled for these times points than when comparing Day 0 to Day 364. 15 participants started the trial, and only 4 completed, thus there were 7 active participants for the Day 84 timepoint.
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.
Outcome measures
| Measure |
Active BCG Immunization
n=7 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Blood Biomarkers of AD Pathology-ATN
Plasma pTau217 (pg/ml)
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0.916 picogram/milliliter (pg/ml)
Standard Deviation 7.179
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Blood Biomarkers of AD Pathology-ATN
Plasma pTau181 (pg/ml)
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0.004 picogram/milliliter (pg/ml)
Standard Deviation 1.288
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Blood Biomarkers of AD Pathology-ATN
Plasma NfL (pg/ml)
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-1.735 picogram/milliliter (pg/ml)
Standard Deviation 7.881
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PRIMARY outcome
Timeframe: Baseline to Day 84Population: Since this outcome was analyzing the average difference between Day 0 and Day 84, there were more participants enrolled for these times points than when comparing Day 0 to Day 364. 15 participants started the trial, and only 4 completed, thus there were 7 active participants for the Day 84 timepoint.
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.
Outcome measures
| Measure |
Active BCG Immunization
n=7 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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CSF Biomarkers of AD Pathology-ATN
CSF tTau (pg/ml)
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8.727 picogram/milliliter (pg/ml)
Standard Deviation 49.826
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CSF Biomarkers of AD Pathology-ATN
CSF pTau181 (pg/ml)
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-2.414 picogram/milliliter (pg/ml)
Standard Deviation 11.793
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CSF Biomarkers of AD Pathology-ATN
CSF NfL (pg/ml)
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-103.161 picogram/milliliter (pg/ml)
Standard Deviation 317.523
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PRIMARY outcome
Timeframe: Baseline to Day 84Population: Since this outcome was analyzing the average difference between Day 0 and Day 84, there were more participants enrolled for these times points than when comparing Day 0 to Day 364. 15 participants started the trial, and only 4 completed, thus there were 7 active participants for the Day 84 timepoint.
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.
Outcome measures
| Measure |
Active BCG Immunization
n=7 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Cognitive Measures (RBANS)
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17.710 score on a scale
Standard Deviation 35.127
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PRIMARY outcome
Timeframe: Baseline to Day 364Change 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.
Outcome measures
| Measure |
Active BCG Immunization
n=4 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Cognitive Measures (RBANS)
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-5.667 score on a scale
Standard Deviation 19.075
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PRIMARY outcome
Timeframe: Baseline to Day 364Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40 ratio) in blood from baseline.
Outcome measures
| Measure |
Active BCG Immunization
n=4 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Amyloid-β42/40 Average Difference in Blood
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-0.001 ratio
Standard Deviation 0.06
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PRIMARY outcome
Timeframe: Baseline to Day 364Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline.
Outcome measures
| Measure |
Active BCG Immunization
n=4 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Amyloid-β42/40 Average Difference in CSF
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0.000 ratio
Standard Deviation 0.002
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PRIMARY outcome
Timeframe: Baseline to Day 84Population: Since this outcome was analyzing the average difference between Day 0 and Day 84, there were more participants enrolled for these times points than when comparing Day 0 to Day 364. 15 participants started the trial, and only 4 completed, thus there were 7 active participants for the Day 84 timepoint.
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in blood from baseline.
Outcome measures
| Measure |
Active BCG Immunization
n=7 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Amyloid-β42/40 Average Difference in Blood - Baseline to Day 84
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0.001 ratio
Standard Deviation 0.005
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PRIMARY outcome
Timeframe: Baseline to Day 84Population: Since this outcome was analyzing the average difference between Day 0 and Day 84, there were more participants enrolled for these times points than when comparing Day 0 to Day 364. 15 participants started the trial, and only 4 completed, thus there were 7 active participants for the Day 84 timepoint.
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline.
Outcome measures
| Measure |
Active BCG Immunization
n=7 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Amyloid-β42/40 Average Difference in CSF - Baseline to Day 84
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-0.001 ratio
Standard Deviation 0.001
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PRIMARY outcome
Timeframe: Baseline to Day 84Population: Since this outcome was analyzing the average difference between Day 0 and Day 84, there were more participants enrolled for these times points than when comparing Day 0 to Day 364. 15 participants started the trial, and only 4 completed, thus there were 7 active participants for the Day 84 timepoint.
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.
Outcome measures
| Measure |
Active BCG Immunization
n=7 Participants
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Blood Biomarkers of Pharmacodynamic Response - Cytokines
Plasma IL-1b (pg/ml)
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-24.320 picograms/mililiter (pg/ml)
Standard Deviation 100.242
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Blood Biomarkers of Pharmacodynamic Response - Cytokines
Plasma IL-2 (pg/ml)
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0.460 picograms/mililiter (pg/ml)
Standard Deviation 48.615
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Blood Biomarkers of Pharmacodynamic Response - Cytokines
Plasma IL-6 (pg/ml)
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-530.279 picograms/mililiter (pg/ml)
Standard Deviation 1926.387
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Blood Biomarkers of Pharmacodynamic Response - Cytokines
Plasma IL-10 (pg/ml)
|
97.486 picograms/mililiter (pg/ml)
Standard Deviation 269.749
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Blood Biomarkers of Pharmacodynamic Response - Cytokines
Plasma TNF-a (pg/ml)
|
12.004 picograms/mililiter (pg/ml)
Standard Deviation 151.302
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Blood Biomarkers of Pharmacodynamic Response - Cytokines
Plasma IFN-g (pg/ml)
|
365.612 picograms/mililiter (pg/ml)
Standard Deviation 926.852
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Adverse Events
Active BCG Immunization
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Active BCG Immunization
n=15 participants at risk
Active BCG immunization
Biological/Vaccine: Bacillus Calmette-Guerin (BCG): 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.
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|---|---|
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Vascular disorders
Elevated Blood Pressure
|
6.7%
1/15 • Number of events 1 • AEs were collected starting at screening through Day 364 Visit for each participant.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place