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

Phase 1
Completed
Conditions
Alzheimer Disease
Interventions
Other: Sterile saline (Placebo)
Registration Number
NCT04920786
Lead Sponsor
TrueBinding, Inc.
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
PlaceboSterile saline (Placebo)0.9% normal saline infused intravenously over 1 hour
TB006 70 mg - 5000 mg IVTB006TB006 infused intravenously over 1 hour
Primary Outcome Measures
NameTimeMethod
Number of subjects and rate of treatment-emergent adverse events, graded by CTCAE Version 5.0, by dose group and all active treatment vs. placeboDay1-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 subjectsThrough 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 subjectsThrough day 75

Dose-response relationship of AEs and SAEs, and other safety outcomes

Secondary Outcome Measures
NameTimeMethod
Anti-TB006 antibodiesThrough Day 75

Number and rate of subjects who develop anti-TB006 antibodies

Pharmacokinetic (PK) profile/parameters: terminal elimination phase half lifeThrough Day 75

PK: t(1/2)

Pharmacokinetic (PK) profile/parameters: volume of distributionThrough Day 75

PK: Vd

Pharmacokinetic (PK) profile/parameters: Area under the plasma concentration versus time curve (AUC) through Day 29Through Day 75

PK:AUC D0-D29

Pharmacokinetic (PK) profile/parameters: Maximum observed plasma concentrationThrough Day 75

PK: Cmax

Pharmacokinetic (PK) profile/parameters: Area under the plasma concentration versus time curve (AUC)Through Day 75

PK: AUC D0-∞

Pharmacokinetic (PK) profile/parameters: total clearanceThrough Day 75

PK: CL

Pharmacokinetic (PK) profile/parameters: Time at which maximum plasma concentration occursThrough Day 75

PK: tmax

Pharmacokinetic (PK) profile/parameters: Extent of CSF distribution as estimated by TB006 CSF concentrationsThrough Day 75

PK: CSF

Safety and tolerabilityThrough 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

Trial Locations

Locations (1)

Collaborative Neuroscience Research, LLC (CNS)

🇺🇸

Long Beach, California, United States

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