Phase 2 Completed N=25 Randomized Triple-blind Treatment

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

Source: ClinicalTrials.gov NCT05074498 ↗

Enrolled (actual)

Serious AEs

3.9%

Results posted

Nov 2023

Primary outcomePrimary: Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) — 5; 4; 1; 2 Participants

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	5; 4; 1; 2; 1; 0	—
PRIMARY Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK)	-1.7; -5.5; -0.7; 5.4; -0.6; -4.0	—
PRIMARY Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein	-0.14; 0.02; -0.03; -0.04; -0.20; 0.12	—
PRIMARY 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	-0.13; 0.17; -0.02; -0.18; -15.4; -2.7	—
PRIMARY Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C	0.06; -0.02; -0.33; -0.14	—
PRIMARY Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium	0.10; -0.15; 0.07; 0.02; -1.0; 0.8	—
PRIMARY Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin	1.209; -0.343; -0.370; -0.246	—
PRIMARY Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets	-0.023; -0.005; 0.005; 0.006; 0.014; 0.003	—
PRIMARY Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH)	-0.40; -0.05; 1.02; -0.34	—
PRIMARY Part 1: Change From Baseline in Hematology Parameter: Hematocrit	0.69; 1.18; 1.18; 0.32	—
PRIMARY Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes	0.039; 0.012; -0.108; 0.024; -0.011; -0.005	—
PRIMARY Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV)	0.80; 2.45; 5.42; 0.20	—
PRIMARY Part 1: Change From Baseline in Hematology Parameter: Hemoglobin	-0.06; 0.00; 0.08; -0.10	—
PRIMARY Part 1: Change From Baseline in Urine Potential of Hydrogen (pH)	-0.36; 0.40; -0.50; -0.80	—
PRIMARY Part 1: Change From Baseline in Urine Specific Gravity	0.003; 0.003; 0.004; 0.007	—
PRIMARY Part 1: Change From Baseline in Urobilinogen	0.00; -0.16; -0.13; 0.00	—
PRIMARY Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	-2.1; -2.3; -1.0; -7.2; -10.4; 3.5	—
PRIMARY Part 1: Change From Baseline in Respiratory Rate	0.0; -0.7; 0.3; -0.2	—
PRIMARY Part 1: Change From Baseline in Temperature	0.26; -0.37; -0.03; -0.22	—
PRIMARY Part 1: Change From Baseline in Heart Rate	-2.0; 3.3; 4.0; -4.2	—
PRIMARY Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate	-4.8; -0.9; 3.0; -3.4	—
PRIMARY Part 1: Change From Baseline in ECG Parameters	4.8; 0.7; -11.0; 14.9; 0.3; 1.1	—
PRIMARY Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)	0; 0; 0; 0; 0; 0	—
PRIMARY Part 1: Number of Participants With Clinically Significant Physical Examination Findings	—	—
PRIMARY Part 1: Number of Participants With Clinically Significant Neurological Examination Findings	—	—
PRIMARY Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006	39.81; 29.87; 11.93; 125.92; 117.75; 82.95	—
PRIMARY Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006	1.12; 2.01; 2.00; 1.23; 1.60; 2.50	—
PRIMARY Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006	0.36; 0.29; 0.07; 0.58; 0.49; 0.30	—
PRIMARY Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006	25.77; 71.44; 68.62; 76.69; 204.77; 348.20	—
PRIMARY Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006	711.49; 757.59; 739.50	—
PRIMARY Part 1: Total Clearance (CL) of TB006	7.94; 8.49; 12.06	—
PRIMARY Part 1: Volume of Distribution (Vd) of TB006	8151.47; 9282.51; 13617.70	—
PRIMARY Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006)	0; 0; 0; 0; 0; 0	—
PRIMARY Part 2: Change From Baseline Through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score	0.01; 0.35	0.0838
SECONDARY Part 2: Change From Baseline Through Day 36 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score	-0.16; 0.23	—
SECONDARY Part 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes	25.4; 9.7; 22.4; 15.3	—
SECONDARY Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score	1.2; 0.2; 1.0; 0.6	—
SECONDARY Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score	-2.5; -0.8; -3.5; -1.1	—
SECONDARY Part 2: Number of Participants With AEs and SAEs	28; 17; 4; 1	—
SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK	-0.5; -0.4; 1.0; 0.0; -0.4; -0.5	—
SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein	-0.10; -0.01; -0.10; 0.00	—
SECONDARY Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen	-0.09; -0.11; -5.8; 0.3; 0.014; -0.017	—
SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C	-0.06; 0.07	—
SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium	-0.14; -0.13; -0.7; -0.7	—
SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin	-0.118; 0.134	—
SECONDARY Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets	-0.004; -0.002; -0.008; -0.040; -0.26; -0.02	—
SECONDARY Part 2: Change From Baseline in Hematology Parameter: Ery. MCH	0.19; 0.51	—
SECONDARY Part 2: Change From Baseline in Hematology Parameter: Ery. MCV	1.54; 2.04	—
SECONDARY Part 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes	-0.028; 0.024; 0.001; -0.003	—
SECONDARY Part 2: Change From Baseline in Hematology Parameter: Hematocrit	0.41; 1.11	—
SECONDARY Part 2: Change From Baseline in Hematology Parameter: Hemoglobin	0.00; 0.29	—
SECONDARY Part 2: Change From Baseline in Urine pH	-0.13; 0.18	—
SECONDARY Part 2: Change From Baseline in Urine Specific Gravity	0.002; 0.001	—
SECONDARY Part 2: Change From Baseline in Urobilinogen	0.07; 0.05	—
SECONDARY Part 2: Change From Baseline in DBP and SBP	0.8; 0.7; 1.4; 0.0	—
SECONDARY Part 2: Change From Baseline in Respiratory Rate	0.1; 0.2	—
SECONDARY Part 2: Change From Baseline in Temperature	0.01; -0.03	—
SECONDARY Part 2: Change From Baseline in Heart Rate	-4.2; -2.1	—
SECONDARY Part 2: Change From Baseline in ECG Parameters	-1.6; 2.1; -2.2; -1.4; 4.2; 3.9	—
SECONDARY Part 2: Change From Baseline in ECG Mean Heart Rate	-1.8; -1.3	—
SECONDARY Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS	0; 0; 0; 0; 0; 0	—
SECONDARY Part 2: Number of Participants With Clinically Significant Physical Examination Findings	—	—
SECONDARY Part 2: Number of Participants With Clinically Significant Neurological Examination Findings	—	—
SECONDARY Part 2: Ctrough of TB006	395.82	—
SECONDARY Part 2: t1/2 of TB006	756.78	—
SECONDARY Part 2: Cmax of TB006	339.17; 731.55	—

Eligibility Criteria

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:
Probable AD, according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)
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

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Data sourced from ClinicalTrials.gov (NCT05074498). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.