Alzheimer's Disease
Conditions
Keywords
Alzheimer's disease, Open-label Extension, TB006, TB006AD2102, De Novo
Brief summary
This is an open-label long term extension study for participants with Alzheimer's disease (AD) who have completed Protocol TB006AD2102 (lead-in study) or participants who would have been eligible for the lead-in study but were not enrolled (de novo). The study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TB006. The total study duration for each participant will be up to 113 weeks.
Detailed description
The total study duration for each participant will be up to 113 weeks \[This includes 101 weeks (2 years) of dosing and a 12-week safety follow-up period\]. The number of participants enrolled from the lead-in study will be 100 to 120 and additionally, up to 50 de novo participants, identified by the sponsor, may be included. A total of approximately 150 to 180 participants will be enrolled.
Interventions
DRUGTB006
Clear to slightly opalescent, sterile solution for injection
Sponsors
TrueBinding, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Lead-in study participants are eligible to be included in the study only if they meet the following criteria: * Completed lead-in Protocol TB006AD2102 (Participants from both study drug and placebo groups) or are eligible for the lead-in study but were not enrolled (de novo). * Eligibility must be reconfirmed by the investigator for participants who have a gap of more than 28 days between lead-in Protocol TB006AD2102 completion and enrolment in the current study. These participants will undergo the screening procedures in the current Open-label extension (OLE) protocol, with the exception of imaging. * Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Females must be of non-childbearing potential. * Participants or caregiver has the ability to understand the purpose and risks of the study and provide signed and dated informed consent. Participants whose caregiver signs the informed consent must provide their assent. * Either currently or previously (in pre-AD condition) literate and capable of reading, writing, and communicating effectively with others. * Participants, along with the caregiver, will be compliant with study visits, procedure. De novo participants, identified by the sponsor and referred to a participating site, are eligible to be included in the study only if all of the following criteria apply: * Male and/or female \> 50 years of age at the time of signing the informed consent. * Body weight of ≥ 50 kilograms (kg) and body mass index (BMI) between 18 and 35 kilograms per square meter (kg/m\^2), inclusive. * MMSE score of 24 or less. * Must be ambulatory. * Clinical diagnosis of AD consistent with the following: 1. Probable AD, according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). 2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) - Criteria for Major Neurocognitive Disorder (previously dementia). * Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Females must be of non-childbearing potential. * Participants or caregiver has the ability to understand the purpose and risks of the study and provide signed and dated informed consent. Participants whose caregiver signs the informed consent must provide their assent. * Either currently or previously (in pre-AD condition) literate and capable of reading, writing, and communicating effectively with others.
Exclusion criteria
Lead-in study participants are excluded from the study if any of the following criteria apply: * Development of an intolerable adverse event or an adverse event that was considered an important safety risk in Protocol TB006AD2102 * Any of the following emerging medical or psychiatric
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events and Serious Adverse Events | Up to 61 weeks | Summary for Number of Participants with Adverse Events and Serious Adverse Events |
| Number of Participants With Clinically Significant Clinical Laboratory Parameter Values | Up to 61 weeks | Summary of participants with Clinically Significant Clinical Laboratory Parameter Values |
| Number of Participants With Clinically Significant Vital Sign Values | Up to 61 weeks | Summary of Participants with Clinically Significant Vital Sign Values |
| Number of Participants With Clinically Significant 12-Lead Electrocardiogram Findings | Up to 61 weeks | Summary of Participants with Clinically Significant 12-Lead electrocardiogram Findings |
| Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) | Baseline and up to 61 weeks | The C-SSRS is a suicidal ideation and behavior rating scale with yes/no responses. For each of the 5 items of the C-SSRS related to suicidal ideation intensity, an individual's degree of suicidal ideation is rated on a 0-5 scale with 0: no suicidal behavior and 5: active suicidal ideation. The total score is the sum of the 5 intensity item scores (total score ranges from 0 to 25). Higher scores in the scale indicate greater disease severity. An increase from baseline in the total score of C-SSRS \>=1 is considered as an adverse change. |
| Plasma Concentration of TB006 | Pre-dose, and Weeks 1, 5, 9, 13, 17, 21, 25, 45, 73, 101, 113 and ED/EOS up to Week 61 | Summary of plasma concentration of TB006 |
| Number of Participants With Anti-TB006 Antibodies | Up to 61 weeks | Summary of Participants with Anti-TB006 Antibodies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Dementia Rating Scale-Sum of Boxes (CDR SB) Score | Baseline and up to Week 101 | The CDR scale is a clinician-rated dementia staging system that tracks the progression of cognitive impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care). Each category is scored on a 5-point scale in which None = 0, Questionable = 0.5, Mild = 1, Moderate = 2, and Severe = 3. The global CDR score is established by clinical scoring rules and has values of 0 (no dementia), 0.5, (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is obtained by adding the ratings in each of the 6 categories and ranges from 0 to 18 with higher scores indicative of greater impairment. |
| Change From Baseline in Mini Mental State Examination (MMSE) Score | Baseline and up to Week 101 | Global cognitive functioning is measured by MMSE. MMSE is a neuropsychological test for the evaluation of intellectual efficiency disorders and the presence of cognitive impairment. The total score is between a minimum of 0 (worse cognitive function) and a maximum of 30 points (normal cognitive function). A lower score indicates severe impairment of cognitive abilities and a higher score indicates cognitive normality. |
| Change From Baseline in Neuropsychiatry Inventory (NPI) Score | Baseline and up to Week 101 | The NPI is a condition-specific measure designed to assess 12 behavioral disturbances, namely delusions, hallucinations, depression/dysphoria, anxiety, agitation/aggression, elation/euphoria, disinhibition, irritability/lability, apathy, aberrant motor activity, night-time behavior disturbances, and appetite/eating abnormalities. The frequency is scored from 0 (never) to 4 (very frequently) and severity ranges between 0 (none) to 3 (marked). The domain score is obtained by multiplying frequency and severity scores. The total NPI score is the sum total of all individual domain scores (0-144). A higher score indicates abnormal behaviour. |
| Change From Baseline in EuroQol 5 Dimension 5-Level Quality of Life (EQ 5D 5L QoL) Total Score | Baseline and up to Week 101 | EuroQol 5 is a self-reported description of participant's current health in 5 dimensions i.e., mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Participants to grade their own current level of function in each dimension into one of three degrees of disability (severe, moderate or none). Score ranges between 1 (no problem) and 3 (significant problem). higher scores indicating higher health utility. The total score is the sum total of all individual domain scores (5-15). Higher scores indicates poor quality of life. |
Countries
United States
Contacts
STUDY_DIRECTORAlan K Jacobs, MD
TrueBinding, Inc.
Participant flow
Recruitment details
This study enrolled adult patients who completed the lead-in Protocol TB006AD2102 (patients from both TB006 treatment and placebo groups) or were eligible for the lead-in study but were not enrolled (de novo). A total of 125 patients were screened, of whom 6 (4.8%) patients were screening failures, 119 patients were included in the study. Study Period: Approximately 14 Months Date of First Enrollment: 15 Sep 2022 Date of Last Completed: 17 Nov 2023 Multicenter, 15 sites in the US.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 73.2 years STANDARD_DEVIATION 8.1 |
| Diagnosis of Alzheimers Disease | 119 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 104 Participants |
| Region of Enrollment United States | 119 participants |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 119 |
| other Total, other adverse events | 37 / 119 |
| serious Total, serious adverse events | 9 / 119 |
Outcome results
None listed