Sequential Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of TB006 in Healthy Subjects

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1 Double-blind, Randomized, Single Dose, Sequential Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of TB006 in Healthy Subjects

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: TB006
* Other: Sterile saline (Placebo)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TB006 70 mg - 5000 mg IV<br>TB006 infused intravenously over 1 hour | Drug: TB006<br>* TB006<br>|
| Placebo Comparator: Placebo<br>0.9% normal saline infused intravenously over 1 hour | Other: Sterile saline (Placebo)<br>* Sterile saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | To measure the incidence of AEs and SAEs, clinical laboratory parameters, and vital signs until Day 75 after dosing. | Day1-Day 75 | 
| To determine the single-dose PK profile of TB006 in healthy adult subjects | PK parameters derived by noncompartmental analysis using the TB006 plasma concentration-time data | Through day 75 | 
| To determine the MTD of single doses of TB006 in healthy adult subjects | Dose-response relationship of AEs and SAEs, and other safety outcomes | Through day 75 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) profile/parameters: Area under the plasma concentration versus time curve (AUC) through Day 29 | PK:AUC D0-D29 | Through Day 75 | 
| Pharmacokinetic (PK) profile/parameters: Area under the plasma concentration versus time curve (AUC) | PK: AUC D0-∞ | Through Day 75 | 
| Pharmacokinetic (PK) profile/parameters: Maximum observed plasma concentration | PK: Cmax | Through Day 75 | 
| Pharmacokinetic (PK) profile/parameters: Time at which maximum plasma concentration occurs | PK: tmax | Through Day 75 | 
| Pharmacokinetic (PK) profile/parameters: terminal elimination phase half life | PK: t(1/2) | Through Day 75 | 
| Pharmacokinetic (PK) profile/parameters: total clearance | PK: CL | Through Day 75 | 
| Pharmacokinetic (PK) profile/parameters: volume of distribution | PK: Vd | Through Day 75 | 
| Pharmacokinetic (PK) profile/parameters: Extent of CSF distribution as estimated by TB006 CSF concentrations | PK: CSF | Through Day 75 | 
| Safety and tolerability | 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 | Through Day 75 | 
| Anti-TB006 antibodies | Number and rate of subjects who develop anti-TB006 antibodies | Through Day 75 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer Disease