Alzheimer's Disease
Conditions
Brief summary
To evaluate the long-term safety, tolerability and potential efficacy, patients who previously participated in V203-AD study (NCT02551809) will be eligible to participate in the extension study and will receive 3 or 5 doses of UB-311 within a 96-week treatment period followed by a 12-week follow-up period.
Interventions
BIOLOGICALUB-311
Intramuscular injection
DRUGPlacebo
Intramuscular injection
Sponsors
United Neuroscience Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Patients who participated in V203-AD trial without major safety concerns; * Stable doses of permitted medications for 3 months before screening; * With a caregiver; * Other inclusion criteria apply
Exclusion criteria
* Clinically significant neurological disease other than Alzheimer's disease * Major psychiatric disorder * Severe systemic disease * Serious adverse reactions to any vaccine * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Adverse Event (AE)/Serious Adverse Event (SAE) [Safety and Tolerability]). | Overall Study Duration/Early Termination, over an average study duration of 326 days | Summary of Treatment Emergent Adverse Events (TEAEs), based on reported adverse events and other safety information including local tolerability at injection site, MRI, vital signs, physical examination, 12-lead ECG and laboratory tests. |
| Change From Baseline and Through to the End of the Study in Anti-Aβ Antibody Titers [The Immunogenicity of UB-311] | Overall Study Duration/Early Termination, over an average study duration of 326 days | For the immunogenicity assessment of the investigational product, UB-311, the level of anti-Aβ antibodies in the serum samples will be measured by a validated enzyme immunoassay manufactured by United Biomedical, Inc. (UBI). The level of anti-Aβ antibodies is assessed at every visit throughout the study period. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline and Through to the End of the Study in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); | Overall Study Duration/Early Termination, over an average study duration of 326 days | The ADAS-Cog 13 contains 13 items, with a total scoring range of 0 - 85 and higher scores indicating greater dysfunction. ADAS-Cog scores were evaluated at V1 and V8/ET. The observed values and change from baseline for ADAS-Cog scores by treatment groups in the extension study are presented |
| Change From Baseline and Through to the End of the Study in Mini-Mental State Exam (MMSE) | Overall Study Duration/Early Termination, over an average study duration of 326 days | The MMSE is a 30-point questionnaire. The total score range is 0 - 30 and lower scores indicating greater impairment. MMSE scores were evaluated at V1 and V8/ET. The observed values and change from baseline for MMSE scores by treatment groups in the extension study are presented |
| Change From Baseline and Through to the End of the Study in Clinical Dementia Rating - Sum of Boxes (CDR-SB) | Overall Study Duration/Early Termination, over an average study duration of 326 days | The CDR-SB includes 6 domains (0 - 3 points/domain), with a total scoring range of 0 - 18 and higher scores indicate greater impartment. CDR-SB scores were evaluated at V1 and V8/ET. The observed values and change from baseline for CDR-SB scores by treatment groups in the extension study are presented |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| M7E1 Treatment Group Arm 1 from V203-AD (M7) received 1 dose of UB-311 and 2 doses of placebo in V203-AD-EXT (E1) | 10 |
| M7E3 Treatment Group Arm 1 from V203-AD (M7) received 3 doses of UB-311 in V203-AD-EXT (E3) | 2 |
| M5E1 Treatment Group Arm 2 from V203-AD (M5) received 1 dose of UB-311 and 2 doses of placebo in V203-AD-EXT (E1) | 7 |
| M5E3 Treatment Group Arm 2 from V203-AD (M5) received 3 doses of UB-311 in V203-AD-EXT (E3) | 5 |
| M0E1 Treatment Group Arm 3 from V203-AD (M0) received 1 dose of UB-311 and 2 doses of placebo in V203-AD-EXT (E1) | 8 |
| M0E3 Treatment Group Arm 3 from V203-AD (M0) received 3 doses of UB-311 in V203-AD-EXT (E3) | 2 |
| Total | 34 |
Baseline characteristics
| Characteristic | M7E1 | M7E3 | M5E1 | M5E3 | M0E1 | M0E3 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 73.2 years STANDARD_DEVIATION 5.81 | 83.0 years STANDARD_DEVIATION 7.07 | 75.4 years STANDARD_DEVIATION 7.74 | 71.6 years STANDARD_DEVIATION 6.8 | 74.9 years STANDARD_DEVIATION 8.31 | 70.5 years STANDARD_DEVIATION 4.95 | 74.2 years STANDARD_DEVIATION 7.06 |
| Mini-Mental State Examination | 17.2 units on a scale STANDARD_DEVIATION 7.05 | 24 units on a scale STANDARD_DEVIATION 4.24 | 18.71 units on a scale STANDARD_DEVIATION 5.74 | 16.4 units on a scale STANDARD_DEVIATION 7.47 | 18.13 units on a scale STANDARD_DEVIATION 5.92 | 20.5 units on a scale STANDARD_DEVIATION 2.12 | 18.21 units on a scale STANDARD_DEVIATION 6.13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 2 Participants | 7 Participants | 5 Participants | 8 Participants | 2 Participants | 34 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 10 Participants | 2 Participants | 7 Participants | 5 Participants | 8 Participants | 2 Participants | 34 Participants |
| Sex: Female, Male Female | 9 Participants | 0 Participants | 4 Participants | 3 Participants | 6 Participants | 2 Participants | 24 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 2 | 0 / 7 | 0 / 5 | 0 / 8 | 0 / 2 |
| other Total, other adverse events | 4 / 10 | 1 / 2 | 2 / 7 | 3 / 5 | 5 / 8 | 1 / 2 |
| serious Total, serious adverse events | 2 / 10 | 0 / 2 | 2 / 7 | 0 / 5 | 1 / 8 | 1 / 2 |
Outcome results
Primary
Change From Baseline and Through to the End of the Study in Anti-Aβ Antibody Titers [The Immunogenicity of UB-311]
For the immunogenicity assessment of the investigational product, UB-311, the level of anti-Aβ antibodies in the serum samples will be measured by a validated enzyme immunoassay manufactured by United Biomedical, Inc. (UBI). The level of anti-Aβ antibodies is assessed at every visit throughout the study period.
Time frame: Overall Study Duration/Early Termination, over an average study duration of 326 days
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| M7E1 | Change From Baseline and Through to the End of the Study in Anti-Aβ Antibody Titers [The Immunogenicity of UB-311] | 0.56 Geometric Mean Ratio in log10 | Standard Deviation 0.72 |
| M7E3 | Change From Baseline and Through to the End of the Study in Anti-Aβ Antibody Titers [The Immunogenicity of UB-311] | 0.11 Geometric Mean Ratio in log10 | Standard Deviation 0.35 |
| M5E1 | Change From Baseline and Through to the End of the Study in Anti-Aβ Antibody Titers [The Immunogenicity of UB-311] | 0.15 Geometric Mean Ratio in log10 | Standard Deviation 0.35 |
| M5E3 | Change From Baseline and Through to the End of the Study in Anti-Aβ Antibody Titers [The Immunogenicity of UB-311] | 0.49 Geometric Mean Ratio in log10 | Standard Deviation 0.32 |
| M0E1 | Change From Baseline and Through to the End of the Study in Anti-Aβ Antibody Titers [The Immunogenicity of UB-311] | 0.10 Geometric Mean Ratio in log10 | Standard Deviation 0.24 |
| M0E3 | Change From Baseline and Through to the End of the Study in Anti-Aβ Antibody Titers [The Immunogenicity of UB-311] | 0.80 Geometric Mean Ratio in log10 | Standard Deviation 0.09 |
Primary
The Incidence of Adverse Event (AE)/Serious Adverse Event (SAE) [Safety and Tolerability]).
Summary of Treatment Emergent Adverse Events (TEAEs), based on reported adverse events and other safety information including local tolerability at injection site, MRI, vital signs, physical examination, 12-lead ECG and laboratory tests.
Time frame: Overall Study Duration/Early Termination, over an average study duration of 326 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M7E1 | The Incidence of Adverse Event (AE)/Serious Adverse Event (SAE) [Safety and Tolerability]). | 4 Participants |
| M7E3 | The Incidence of Adverse Event (AE)/Serious Adverse Event (SAE) [Safety and Tolerability]). | 1 Participants |
| M5E1 | The Incidence of Adverse Event (AE)/Serious Adverse Event (SAE) [Safety and Tolerability]). | 4 Participants |
| M5E3 | The Incidence of Adverse Event (AE)/Serious Adverse Event (SAE) [Safety and Tolerability]). | 3 Participants |
| M0E1 | The Incidence of Adverse Event (AE)/Serious Adverse Event (SAE) [Safety and Tolerability]). | 5 Participants |
| M0E3 | The Incidence of Adverse Event (AE)/Serious Adverse Event (SAE) [Safety and Tolerability]). | 2 Participants |
Other Pre-specified
Change From Baseline and Through to the End of the Study in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog);
The ADAS-Cog 13 contains 13 items, with a total scoring range of 0 - 85 and higher scores indicating greater dysfunction. ADAS-Cog scores were evaluated at V1 and V8/ET. The observed values and change from baseline for ADAS-Cog scores by treatment groups in the extension study are presented
Time frame: Overall Study Duration/Early Termination, over an average study duration of 326 days
Population: If more than one of 13 items of ADAS-Cog were missing/not available, ADASCog-13 total score was set to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| M7E1 | Change From Baseline and Through to the End of the Study in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); | 2.86 score on a scale | Standard Deviation 4.811 |
| M7E3 | Change From Baseline and Through to the End of the Study in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); | -0.50 score on a scale | Standard Deviation 2.121 |
| M5E1 | Change From Baseline and Through to the End of the Study in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); | 2.50 score on a scale | Standard Deviation 4.324 |
| M5E3 | Change From Baseline and Through to the End of the Study in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); | 5.67 score on a scale | Standard Deviation 3.512 |
| M0E1 | Change From Baseline and Through to the End of the Study in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); | 3.50 score on a scale | Standard Deviation 3.564 |
| M0E3 | Change From Baseline and Through to the End of the Study in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); | 1.00 score on a scale | Standard Deviation 1.414 |
Other Pre-specified
Change From Baseline and Through to the End of the Study in Clinical Dementia Rating - Sum of Boxes (CDR-SB)
The CDR-SB includes 6 domains (0 - 3 points/domain), with a total scoring range of 0 - 18 and higher scores indicate greater impartment. CDR-SB scores were evaluated at V1 and V8/ET. The observed values and change from baseline for CDR-SB scores by treatment groups in the extension study are presented
Time frame: Overall Study Duration/Early Termination, over an average study duration of 326 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| M7E1 | Change From Baseline and Through to the End of the Study in Clinical Dementia Rating - Sum of Boxes (CDR-SB) | 1.50 score on a scale | Standard Deviation 2.483 |
| M7E3 | Change From Baseline and Through to the End of the Study in Clinical Dementia Rating - Sum of Boxes (CDR-SB) | 0.00 score on a scale | Standard Deviation 0 |
| M5E1 | Change From Baseline and Through to the End of the Study in Clinical Dementia Rating - Sum of Boxes (CDR-SB) | 0.64 score on a scale | Standard Deviation 1.345 |
| M5E3 | Change From Baseline and Through to the End of the Study in Clinical Dementia Rating - Sum of Boxes (CDR-SB) | 2.00 score on a scale | Standard Deviation 3.082 |
| M0E1 | Change From Baseline and Through to the End of the Study in Clinical Dementia Rating - Sum of Boxes (CDR-SB) | 3.69 score on a scale | Standard Deviation 4.869 |
| M0E3 | Change From Baseline and Through to the End of the Study in Clinical Dementia Rating - Sum of Boxes (CDR-SB) | 0.75 score on a scale | Standard Deviation 1.061 |
Other Pre-specified
Change From Baseline and Through to the End of the Study in Mini-Mental State Exam (MMSE)
The MMSE is a 30-point questionnaire. The total score range is 0 - 30 and lower scores indicating greater impairment. MMSE scores were evaluated at V1 and V8/ET. The observed values and change from baseline for MMSE scores by treatment groups in the extension study are presented
Time frame: Overall Study Duration/Early Termination, over an average study duration of 326 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| M7E1 | Change From Baseline and Through to the End of the Study in Mini-Mental State Exam (MMSE) | -1.80 score on a scale | Standard Deviation 3.225 |
| M7E3 | Change From Baseline and Through to the End of the Study in Mini-Mental State Exam (MMSE) | -1.50 score on a scale | Standard Deviation 2.121 |
| M5E1 | Change From Baseline and Through to the End of the Study in Mini-Mental State Exam (MMSE) | -0.57 score on a scale | Standard Deviation 1.618 |
| M5E3 | Change From Baseline and Through to the End of the Study in Mini-Mental State Exam (MMSE) | -3.00 score on a scale | Standard Deviation 4.183 |
| M0E1 | Change From Baseline and Through to the End of the Study in Mini-Mental State Exam (MMSE) | -4.38 score on a scale | Standard Deviation 4.868 |
| M0E3 | Change From Baseline and Through to the End of the Study in Mini-Mental State Exam (MMSE) | -2.00 score on a scale | Standard Deviation 2.828 |