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

Phase 1

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: TB006
Drug: Placebo

Registration Number: NCT05074498

Lead Sponsor: TrueBinding, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 154

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 & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1: TB006	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.
Part 1: Placebo	Placebo	Participants will be randomized to receive 5 once-weekly doses of matching placebo.
Part 2: Placebo	Placebo	Participants will be randomized to receive matching placebo. Randomization will be stratified according to severity at Baseline (mild versus moderate Alzheimer's Disease).
Part 2: TB006	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).

Primary Outcome Measures

Name	Time	Method
Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein	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	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	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	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	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)	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	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)	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)	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	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)	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)	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	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	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	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	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	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	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)	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)	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	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	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	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	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	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	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	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	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	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	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	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	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	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)	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.

Secondary Outcome Measures

Name	Time	Method
Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score	Baseline and at Days 36 and 104	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.
Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK	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 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen	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 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes	At Days 36 and 104	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.
Part 2: Change From Baseline Through Day 36 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score	Baseline through Day 36	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 2: Number of Participants With AEs and SAEs	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 2: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C	Baseline and up to Day 104	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.
Part 2: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin	Baseline and up to Day 104	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.
Part 2: Change From Baseline in Hematology Parameter: Hemoglobin	Baseline and up to Day 104	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.
Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score	Baseline and at Days 36 and 104	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.
Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein	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 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium	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 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets	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 2: Change From Baseline in Hematology Parameter: Hematocrit	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 2: Change From Baseline in Urobilinogen	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 2: Change From Baseline in Hematology Parameter: Ery. MCH	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 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes	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 2: Change From Baseline in Urine Specific Gravity	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 2: t1/2 of TB006	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 in Hematology Parameter: Ery. MCV	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 2: Change From Baseline in Urine pH	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 2: Change From Baseline in DBP and SBP	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 2: Change From Baseline in Temperature	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). 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 2: Change From Baseline in ECG Parameters	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 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 2: Number of Participants With Clinically Significant Physical Examination Findings	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 2: Ctrough of TB006	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: Cmax of TB006	Day 1 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 2: Change From Baseline in Respiratory Rate	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). 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 2: Change From Baseline in Heart Rate	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). 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 2: Change From Baseline in ECG Mean Heart Rate	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.
Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS	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 2: Number of Participants With Clinically Significant Neurological Examination Findings	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.