Alzheimer Disease
Conditions
Keywords
Alzheimer Disease
Brief summary
This is a single dose, dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of TB006, a monoclonal antibody that will be studied as a disease modifying treatment for Alzheimer's disease.
Detailed description
The TB006 nonclinical pharmacology program establishes its potential as a therapeutic agent for AD. Overall, the data suggest the potential for beneficial therapeutic effects of TB006 in addressing underlying pathology and ameliorating the course of AD. The preclinical safety profile of TB006 further supports the clinical investigation of TB006. This is a Phase 1 SAD study in healthy adult subjects. The study will evaluate the safety, tolerability, and PK of single doses of TB006, administered as an IV infusion over 1 hour.
Interventions
DRUGTB006
TB006
Sterile saline
Sponsors
TrueBinding, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Six dose groups are planned: 5 dose levels of TB006 in healthy subjects and 1 ethno-bridging group in healthy subjects of Chinese descent.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers, male or female 18-55 at the time of informed consent * In good health as determined by the principal investigator * Body weight of ≥ 50 kg and BMI within the range 18-30 kg/m2 (inclusive). * Chinese subjects are eligible to be included in the study if all of the following criteria apply in addition to the above: Must have been born in China, with 2 Chinese biological parents and 4 Chinese grandparents as confirmed by interview; Must have lived no more than 10 years outside of China; Must not have changed their lifestyle or habits significantly, including diet, since leaving China.
Exclusion criteria
* Any current history of clinically significant disease in the opinion of the investigator or receiving maintenance medications on a daily basis. * Any active or unstable clinically significant medical or psychiatric condition as judged by the investigator. * Smokes cigarettes or uses other nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers), and has done so in the 3 months prior to screening. * Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of \> 20 units for males or \> 16 units for females. One unit is equivalent to 8 glasses of alcohol: a half pint (∼240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects and rate of treatment-emergent adverse events, graded by CTCAE Version 5.0, by dose group and all active treatment vs. placebo | Day1-Day 75 | To measure the incidence of AEs and SAEs, clinical laboratory parameters, and vital signs until Day 75 after dosing. |
| To determine the single-dose PK profile of TB006 in healthy adult subjects | Through day 75 | PK parameters derived by noncompartmental analysis using the TB006 plasma concentration-time data |
| To determine the MTD of single doses of TB006 in healthy adult subjects | Through day 75 | Dose-response relationship of AEs and SAEs, and other safety outcomes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) profile/parameters: Time at which maximum plasma concentration occurs | Through Day 75 | PK: tmax |
| Pharmacokinetic (PK) profile/parameters: terminal elimination phase half life | Through Day 75 | PK: t(1/2) |
| Pharmacokinetic (PK) profile/parameters: total clearance | Through Day 75 | PK: CL |
| Pharmacokinetic (PK) profile/parameters: Area under the plasma concentration versus time curve (AUC) through Day 29 | Through Day 75 | PK:AUC D0-D29 |
| Pharmacokinetic (PK) profile/parameters: Extent of CSF distribution as estimated by TB006 CSF concentrations | Through Day 75 | PK: CSF |
| Safety and tolerability | Through Day 75 | Number of subjects and rate of treatment-emergent adverse events, graded by CTCAE Version 5.0, by dose group and all active treatment vs. placebo in non-Chinese healthy and Chinese healthy subjects |
| Anti-TB006 antibodies | Through Day 75 | Number and rate of subjects who develop anti-TB006 antibodies |
| Pharmacokinetic (PK) profile/parameters: volume of distribution | Through Day 75 | PK: Vd |
| Pharmacokinetic (PK) profile/parameters: Area under the plasma concentration versus time curve (AUC) | Through Day 75 | PK: AUC D0-∞ |
| Pharmacokinetic (PK) profile/parameters: Maximum observed plasma concentration | Through Day 75 | PK: Cmax |
Countries
United States
Outcome results
None listed