Sequential Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of TB006 in Healthy Subjects (TB006SAD)

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: TB006; Other: Sterile saline (Placebo)

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research, LLC (CNS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: TrueBinding, Inc.
• Investigators: Study Director: George Haig, PharmD, TrueBinding, Inc.; Principal Investigator: David Walling, MD, Collaborative Neuroscience Research

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): May 3, 2022
• Study Completion (Actual): May 3, 2022

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: TB006HV1101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No