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

• ClinicalTrials.gov Identifier: NCT04920786
• Recruitment Status: Unknown
• First Posted: June 10, 2021
• Last Update Posted: June 10, 2021
• Sponsor: TrueBinding, Inc.
• Information provided by (Responsible Party): TrueBinding, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Drug: TB006; Other: Sterile saline (Placebo)	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• 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.
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Double-blind, Randomized, Single Dose, Sequential Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of TB006 in Healthy Subjects
• Actual Study Start Date: June 1, 2021
• Estimated Primary Completion Date: November 30, 2022
• Estimated Study Completion Date: January 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Anna Cabral; 714-891-0971; annecabral@cnstrial.com

Locations

United States, California

Collaborative Neuroscience Research, LLC (CNS); Recruiting

Long Beach, California, United States, 90806

Contact: Anne Cabral

Contact: David Walling, PhD

Sponsors and Collaborators

TrueBinding, Inc.

Investigators

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

More Information

• Responsible Party: TrueBinding, Inc.
• ClinicalTrials.gov Identifier: NCT04920786
• Other Study ID Numbers: TB006HV1101
• First Posted: June 10, 2021
• Last Update Posted: June 10, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by TrueBinding, Inc.:

Alzheimer Disease

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders