Clinical trial NCT05074498: Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of TB006 in Participants With Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alzheimer's Disease
Keywords: TB006
pharmacokinetics
pharmacodynamics
immunogenicity
mild to severe Alzheimer's Disease
Lead sponsor: TrueBinding, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-12
Enrollment: 154
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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:

  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

Primary outcomes:
measure: Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 104
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK)
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
timeFrame: Baseline and up to Day 104
measure: 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
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH)
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV)
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Urine Potential of Hydrogen (pH)
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Urine Specific Gravity
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Urobilinogen
timeFrame: Baseline and up to Day 104
measure: Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: Baseline and Up to Day 104
measure: Part 1: Change From Baseline in Respiratory Rate
timeFrame: Baseline and Up to Day 104
measure: Part 1: Change From Baseline in Temperature
timeFrame: Baseline and Up to Day 104
measure: Part 1: Change From Baseline in Heart Rate
timeFrame: Baseline and Up to Day 104
measure: Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate
timeFrame: Baseline and Up to Day 104
measure: Part 1: Change From Baseline in ECG Parameters
timeFrame: Baseline and Up to Day 104
measure: Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Day 104
measure: Part 1: Number of Participants With Clinically Significant Physical Examination Findings
timeFrame: Up to Day 104
measure: Part 1: Number of Participants With Clinically Significant Neurological Examination Findings
timeFrame: Up to Day 104
measure: Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006
timeFrame: Day 1 and Day 29
measure: Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006
timeFrame: At Days 1, 8 and 29
measure: Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006
timeFrame: At Days 1, 8 and 29
measure: Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006
timeFrame: Day 8 and Day 29
measure: Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006
timeFrame: At Day 29
measure: Part 1: Total Clearance (CL) of TB006
timeFrame: At Day 29
measure: Part 1: Volume of Distribution (Vd) of TB006
timeFrame: At Day 29
measure: Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006)
timeFrame: Day 1 (Predose), Day 8 (Predose), Day 36 and Day 104
measure: Part 2: Change From Baseline Through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score
timeFrame: Baseline through Day 104
Secondary outcomes:
measure: Part 2: Change From Baseline Through Day 36 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score
timeFrame: Baseline through Day 36
measure: Part 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes
timeFrame: At Days 36 and 104
measure: Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score
timeFrame: Baseline and at Days 36 and 104
measure: Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score
timeFrame: Baseline and at Days 36 and 104
measure: Part 2: Number of Participants With AEs and SAEs
timeFrame: Up to Day 104
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Hematology Parameter: Ery. MCH
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Hematology Parameter: Ery. MCV
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Urine pH
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Urine Specific Gravity
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in Urobilinogen
timeFrame: Baseline and up to Day 104
measure: Part 2: Change From Baseline in DBP and SBP
timeFrame: Baseline and Up to Day 104
measure: Part 2: Change From Baseline in Respiratory Rate
timeFrame: Baseline and Up to Day 104
measure: Part 2: Change From Baseline in Temperature
timeFrame: Baseline and Up to Day 104
measure: Part 2: Change From Baseline in Heart Rate
timeFrame: Baseline and Up to Day 104
measure: Part 2: Change From Baseline in ECG Parameters
timeFrame: Baseline and Up to Day 104
measure: Part 2: Change From Baseline in ECG Mean Heart Rate
timeFrame: Baseline and Up to Day 104
measure: Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS
timeFrame: Up to Day 104
measure: Part 2: Number of Participants With Clinically Significant Physical Examination Findings
timeFrame: Up to Day 104
measure: Part 2: Number of Participants With Clinically Significant Neurological Examination Findings
timeFrame: Up to Day 104
measure: Part 2: Ctrough of TB006
timeFrame: Day 29
measure: Part 2: t1/2 of TB006
timeFrame: Day 29
measure: Part 2: Cmax of TB006
timeFrame: Day 1 and Day 29
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Clinical Trial Site
state: California
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: Delray Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Lady Lake
country: United States
facility: Clinical Trial Site
state: Florida
city: Maitland
country: United States
facility: Clinical Trial Site #1
state: Florida
city: Maitland
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Stuart
country: United States
facility: Clinical Trial Site
state: Florida
city: West Palm Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Winter Park
country: United States
facility: Clinical Trial Site
state: Florida
city: Winter Park
country: United States
facility: Clinical Trial Site
state: Florida
city: Decatur
country: United States
facility: Clinical Trial Site
state: Georgia
city: Matthews
country: United States
facility: Clinical Trial Site
state: North Carolina
city: DeSoto
country: United States
facility: Clinical Trial Site
state: Texas
city: Fairfax
country: United States
facility: Clinical Trial Site
state: Virginia
Study officials:
affiliation: TrueBinding, Inc.
name: TrueBinding, Inc.
role: STUDY_DIRECTOR
References: