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: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C

时间窗: Baseline and up to Day 104

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.

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

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Urine Specific Gravity

时间窗: Baseline and up to Day 104

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.

Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

时间窗: Up to Day 104

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.

Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH)

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK)

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV)

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Urine Potential of Hydrogen (pH)

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate

时间窗: Baseline and Up to Day 104

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.

Part 1: Change From Baseline in ECG Parameters

时间窗: Baseline and Up to Day 104

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.

Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006

时间窗: Day 1 and Day 29

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.

Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006

时间窗: Day 8 and Day 29

Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Hematology Parameter: Hematocrit

时间窗: Baseline and up to Day 104

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.

Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)

时间窗: Up to Day 104

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.

Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

时间窗: Baseline and Up to Day 104

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.

Part 1: Change From Baseline in Respiratory Rate

时间窗: Baseline and Up to Day 104

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.

Part 1: Total Clearance (CL) of TB006

时间窗: At Day 29

Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

Part 2: Change From Baseline Through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score

时间窗: Baseline through Day 104

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.

Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Temperature

时间窗: Baseline and Up to Day 104

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.

Part 1: Number of Participants With Clinically Significant Physical Examination Findings

时间窗: Up to Day 104

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.

Part 1: Number of Participants With Clinically Significant Neurological Examination Findings

时间窗: Up to Day 104

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.

Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006

时间窗: At Days 1, 8 and 29

Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

Part 1: Volume of Distribution (Vd) of TB006

时间窗: At Day 29

Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

Part 1: Change From Baseline in Urobilinogen

时间窗: Baseline and up to Day 104

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.

Part 1: Change From Baseline in Heart Rate

时间窗: Baseline and Up to Day 104

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.

Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006

时间窗: At Days 1, 8 and 29

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.

Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006

时间窗: At Day 29

Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.

Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006)

时间窗: Day 1 (Predose), Day 8 (Predose), Day 36 and Day 104

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.