Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of TB006 in Participants With Alzheimer's Disease

A Seamless Phase 1b/2a Double-blind, Randomized, Multiple Dose, Multi-center, Sequential Dose-escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of TB006 in Patients With Mild to Severe Alzheimer's Disease

Part 1 of this study will be conducted to determine the safety, tolerability, and pharmacokinetic (PK) profile of multiple doses of TB006, as well as the maximum tolerated dose of TB006, and to assess the immunogenicity of TB006 (production of anti-TB006 antibody). Part 2 of this study will be conducted to determine the clinical efficacy of TB006 in participants with mild to severe Alzheimer's Disease.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: TB006

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Garden Grove, California, United States, 92845
      • Clinical Trial Site
    • San Diego, California, United States, 92103
      • Clinical Trial Site
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Clinical Trial Site
    • Lady Lake, Florida, United States, 32159
      • Clinical Trial Site
    • Maitland, Florida, United States, 32751
      • Clinical Trial Site
    • Maitland, Florida, United States, 32751
      • Clinical Trial Site #1
    • Miami, Florida, United States, 33126
      • Clinical Trial Site
    • Miami, Florida, United States, 33135
      • Clinical Trial Site
    • Miami, Florida, United States, 33137
      • Clinical Trial Site
    • Miami, Florida, United States, 33165
      • Clinical Trial Site
    • Stuart, Florida, United States, 34997
      • Clinical Trial Site
    • West Palm Beach, Florida, United States, 33407
      • Clinical Trial Site
    • Winter Park, Florida, United States, 32789
      • Clinical Trial Site
    • Winter Park, Florida, United States, 32792
      • Clinical Trial Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Clinical Trial Site
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • Clinical Trial Site
  • Texas
    • DeSoto, Texas, United States, 75115
      • Clinical Trial Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body weight of ≥ 50 kilograms (kg) and body mass index (BMI) between 18 and 35 kg/meters squared (m^2), inclusive
• Mini-Mental State Examination (MMSE) score of 24 or less
• Must be ambulatory

• Clinical diagnosis of Alzheimer's Disease (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)
• Participants or caregiver has the ability to understand the purpose and risks of the study and provide signed and dated informed consent which includes compliance with the requirements and restrictions listed in the inform consent form (ICF) and in this protocol. Participants whose caregiver signs the informed consent must provide their assent.

Exclusion Criteria:

• Any medical or neurological condition other than AD that in the opinion of the investigator could be a contributing cause of the participant's dementia (e.g., medication use, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, diffuse Lewy body disease, head trauma)
• History within the past 6 months or evidence of clinically significant psychiatric illness (e.g., major depression, schizophrenia, or bipolar affective disorder)
• Diagnosis of a dementia-related central nervous system (CNS) disease other than AD (e.g., Parkinson's Disease, Huntington's Disease, frontotemporal dementia, multi-infarct dementia, dementia with Lewy bodies, normal pressure hydrocephalus)
• Identification of other known cause of dementia or any other clinically significant contributing co-morbid pathologies at screening magnetic resonance imaging (MRI), in the opinion of the investigator
• Participation in any other drug, biologic, device, or clinical study or treatment with any investigational drug or approved therapy for investigational use within 30 days (or 5 half lives, whichever is longer) prior to screening, and/or participation in any other clinical study involving experimental medications for AD within the 60 days (or 5 half lives, whichever is longer) prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: TB006; Participants will be randomized to 1 of 3 ascending dose groups to receive a total of 5 once-weekly doses of TB006, infused over 1 hour.	Drug: TB006; intravenous infusion
Placebo Comparator: Part 1: Placebo; Participants will be randomized to receive 5 once-weekly doses of matching placebo.	Drug: Placebo; intravenous infusion
Experimental: Part 2: TB006; Participants will receive the highest safe and well-tolerated dose identified in Part 1, infused over 1 hour. Randomization will be stratified according to severity at Baseline (mild versus moderate Alzheimer's Disease).	Drug: TB006; intravenous infusion
Placebo Comparator: Part 2: Placebo; Participants will be randomized to receive matching placebo. Randomization will be stratified according to severity at Baseline (mild versus moderate Alzheimer's Disease).	Drug: Placebo; intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement.	Up to Day 104
Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK)	Blood samples were collected for analysis of following clinical chemistry parameters including ALT, ALP, AST and CK. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein	Blood samples were collected for analysis of following clinical chemistry parameters including albumin and protein. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen	Blood samples were collected for analysis of following clinical chemistry parameters including Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C	Blood samples were collected for analysis of following clinical chemistry parameters including Hemoglobin A1C. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium	Blood samples were collected for analysis of following clinical chemistry parameters including Potassium and Sodium. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin	Blood samples were collected for analysis of following clinical chemistry parameters including Thyrotropin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets	Blood samples were collected for analysis of following hematology parameters including Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH)	Blood samples were collected for analysis of following hematology parameter: Ery. MCH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Hematology Parameter: Hematocrit	Blood samples were collected for analysis of following hematology parameter: Hematocrit. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes	Blood samples were collected for analysis of following hematology parameter: Erythrocytes and Reticulocytes. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV)	Blood samples were collected for analysis of following hematology parameter: Ery. MCV. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Hematology Parameter: Hemoglobin	Blood samples were collected for analysis of following hematology parameter: Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Urine Potential of Hydrogen (pH)	Urine samples were collected for analysis of Urine pH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Urine Specific Gravity	Urine samples were collected for analysis of Urine specific gravity. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Urobilinogen	Urine samples were collected for analysis of Urobilinogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	Vital signs including DBP and SBP was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 1: Change From Baseline in Respiratory Rate	Vital signs including respiratory rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 1: Change From Baseline in Temperature	Vital signs including temperature was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 1: Change From Baseline in Heart Rate	Vital signs including heart rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate	12-lead ECG measurements was obtained using an ECG machine that automatically calculates the heart rate. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value value.	Baseline and Up to Day 104
Part 1: Change From Baseline in ECG Parameters	12-lead ECG measurements was obtained using an ECG machine that automatically calculates the PR interval, QRS duration, QT interval and QT Corrected using Bazett's formula (QTcB). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) were reported. The total score ranges from 0 (no ideation present) to 5 (active suicidal ideation with specific plan and intent); higher scores indicate worse symptoms.	Up to Day 104
Part 1: Number of Participants With Clinically Significant Physical Examination Findings	A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.	Up to Day 104
Part 1: Number of Participants With Clinically Significant Neurological Examination Findings	The neurological examination assessed mental status, motor and sensory skills, hearing and speech, vision, coordination, and balance. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.	Up to Day 104
Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. AUCtau normalized to the actual administered dose is presented. The AUCtau was divided by the actual dose strength to get the normalized area under the concentration-time curve.	Day 1 and Day 29
Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006	Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.	At Days 1, 8 and 29
Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006	Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. Cmax normalized to the actual administered dose is presented. The Cmax was divided by the actual dose strength to get the normalized maximum observed plasma concentration.	At Days 1, 8 and 29
Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006	Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.	Day 8 and Day 29
Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006	Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.	At Day 29
Part 1: Total Clearance (CL) of TB006	Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.	At Day 29
Part 1: Volume of Distribution (Vd) of TB006	Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.	At Day 29
Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006)	Plasma samples were collected at indicated time points for the determination of anti-TB006 antibodies. Plasma samples were screened for antibodies binding to TB006 and the titer of confirmed positive samples has been reported.	Day 1 (Predose), Day 8 (Predose), Day 36 and Day 104
Part 2: Change From Baseline Through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score	The Clinical Dementia Rating was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain was rated on a five-point scale of functioning as follows: 0: no impairment; 0.5: questionable impairment; 1: mild impairment; 2: moderate impairment; and 3: severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes was based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. Baseline was defined as the last available value prior to the subject receiving the first study drug infusion on Day 1. Change from Baseline value was obtained by subtracting Baseline value from post-dose visit value.	Baseline through Day 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Change From Baseline Through Day 36 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score	The Clinical Dementia Rating was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain was rated on a five-point scale of functioning as follows: 0: no impairment; 0.5: questionable impairment; 1: mild impairment; 2: moderate impairment; and 3: severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes was based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. Baseline was defined as the last available value prior to the subject receiving the first study drug infusion on Day 1. Change from Baseline value was obtained by subtracting Baseline value from post-dose visit value.	Baseline through Day 36
Part 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes	The Clinical Dementia Rating is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. A responder was defined as a participant with at least 1 point improvement from Baseline on the Sum of Boxes score. Percentage of responders on the Clinical Dementia Rating Scale - Sum of Boxes has been presented.	At Days 36 and 104
Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score	The MMSE was used to measure cognitive impairment. The MMSE can evaluate overall cognitive function, and is widely used for the assessment of cognitive impairment in dementia participants. The questionnaire consists of 11 items, and each item aims to evaluate different cognitive domains such as orientation, memory, attention, and construction. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from Baseline. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and at Days 36 and 104
Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score	The NPI was a questionnaire that quantified psychiatric symptoms and behavioral disorders in dementia. A total of 12 items (the original NPI-10 consisting of 10 behavioral domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor behavior, The NPI total score was calculated by adding the scores of the domains (each domain scores ranges from 0 to 12). The NPI total score ranges from 0 to 120 with higher scores indicating greater behavioral impairment. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and at Days 36 and 104
Part 2: Number of Participants With AEs and SAEs	An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement.	Up to Day 104
Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK	Blood samples were collected for analysis of following clinical chemistry parameters including ALT, ALP, AST and CK. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein	Blood samples were collected for analysis of following clinical chemistry parameters including albumin and protein. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen	Blood samples were collected for analysis of following clinical chemistry parameters including Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C	Blood samples were collected for analysis of following clinical chemistry parameter including Hemoglobin A1C. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium	Blood samples were collected for analysis of following clinical chemistry parameters including Potassium and Sodium. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin	Blood samples were collected for analysis of following clinical chemistry parameter including Thyrotropin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets	Blood samples were collected for analysis of following hematology parameters including Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Hematology Parameter: Ery. MCH	Blood samples were collected for analysis of following hematology parameter: Ery. MCH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Hematology Parameter: Ery. MCV	Blood samples were collected for analysis of following hematology parameter: Ery. MCV. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes	Blood samples were collected for analysis of following hematology parameter: Erythrocytes and Reticulocytes. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Hematology Parameter: Hematocrit	Blood samples were collected for analysis of following hematology parameter: Hematocrit. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Hematology Parameter: Hemoglobin	Blood samples were collected for analysis of following hematology parameter: Hemoglobin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Urine pH	Urine samples were collected for analysis of Urine pH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Urine Specific Gravity	Urine samples were collected for analysis of Urine specific gravity. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in Urobilinogen	Urine samples were collected for analysis of Urobilinogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.	Baseline and up to Day 104
Part 2: Change From Baseline in DBP and SBP	Vital signs including DBP and SBP was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 2: Change From Baseline in Respiratory Rate	Vital signs including respiratory rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 2: Change From Baseline in Temperature	Vital signs including temperature was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 2: Change From Baseline in Heart Rate	Vital signs including heart rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 2: Change From Baseline in ECG Parameters	12-lead ECG measurements was obtained using an ECG machine that automatically calculates the PR interval, QRS duration, QT interval and QTcB. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 2: Change From Baseline in ECG Mean Heart Rate	12-lead ECG measurements was obtained using an ECG machine that automatically calculates the heart rate. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.	Baseline and Up to Day 104
Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS	The C-SSRS is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) were reported. The total score ranges from 0 (no ideation present) to 5 (active suicidal ideation with specific plan and intent); higher scores indicate worse symptoms.	Up to Day 104
Part 2: Number of Participants With Clinically Significant Physical Examination Findings	A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.	Up to Day 104
Part 2: Number of Participants With Clinically Significant Neurological Examination Findings	The neurological examination assessed mental status, motor and sensory skills, hearing and speech, vision, coordination, and balance. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.	Up to Day 104
Part 2: Ctrough of TB006	Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.	Day 29
Part 2: t1/2 of TB006	Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.	Day 29
Part 2: Cmax of TB006	Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.	Day 1 and Day 29

Collaborators and Investigators

• Sponsor: TrueBinding, Inc.
• Investigators: Study Director: Truebinding, Inc., TrueBinding, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2021
• Primary Completion (Actual): October 13, 2022
• Study Completion (Actual): October 13, 2022

Study Registration Dates

• First Submitted: September 24, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: pharmacokinetics; immunogenicity; pharmacodynamics; TB006; mild to severe Alzheimer's Disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: TB006AD2102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No