A Single and Multiple Dosing Study Targeting Biparatopic Antibody CD38 in Healthy Volunteers

A Phase 1, Double-blind, Single- and Multiple-ascending Dose Escalation Study of TNB-738, a Biparatopic Antibody Targeting CD38 in Healthy Volunteers

This is a Phase 1, Double blind, Single ascending and Multiple ascending dose (SAD and MAD) escalation study in Healthy Volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: TNB-738

Detailed Description

TNB-738 is a fully human bispecific antibody used to inhibit human CD38 enzyme.

The study will consist of 2 arms (A and B). The SAD arm (Arm A) of the study consists of sequential single dose escalation cohorts, whereas the MAD portion (Arm B) of the study consists of sequential dose escalation cohorts receiving study drug once every 4 weeks for 3 doses. In both Arm A and Arm B, subjects will be randomized to receive either TNB-738 or matching placebo.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Q-Pharm Pty Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male or female
2. Age 18 - 75
3. Body mass index (BMI) ranging between 18 and 35 kg/m2, inclusive
4. Female subjects of child-bearing potential must agree to use one of the study-approved effective contraceptive methods for the duration of the study
5. Male subjects must practice true abstinence or agree to use a condom while participating in the study through End of study (EOS)
6. If female, a negative serum pregnancy test at Screening and urinary pregnancy test at Day -1 is required
7. Able to read, understand, and provide signed informed consent
8. Able to communicate adequately with the investigator and to comply with the requirements for the entire study.

Exclusion Criteria:

1. Subject has any significant medical condition that would prevent the subject from participating in the study.
2. Subject is pregnant or breastfeeding.
3. Subject is currently receiving treatment with a biologic agent.
4. Subject has a history of anaphylactic reactions to biologic agents.
5. Subject has been dosed with another investigational drug study within 60 days prior to study drug administration.
6. Subject has current or recent (within 4 weeks prior to screening) signs or symptoms of infection that require antibiotic administration.
7. Subject has evidence of COVID-19 infection and/or subject is deemed at risk for the coronavirus disease in the opinion of the investigator or the subject has participated in another clinical study involving treatment(s), which may increase such risk.
8. Subject has used any prescription (excluding hormonal birth control) drugs within 14 days or illicit drugs within 30 days, or 5 half-lives (whichever is longer), prior to study drug administration.
9. Subject has a positive urine drug test or alcohol breath test at screening.
10. Subject has donated or lost more than 1 unit of blood (500 mL) within 60 days or more than 1 unit of serum within 7 days before the study drug administration.
11. Subject is HIV, HBV, or HCV positive.
12. Subject has received a live virus vaccine within 4 weeks of dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose (SAD -Arm A); Up to 5 cohorts of subjects receiving sequentially ascending dose of TNB-738 or placebo are planned until maximum tolerated dose is reached or recommended phase 2 dose is identified	Drug: TNB-738; TNB-738 is an investigation drug. Other: Matching placebo
Experimental: Multiple Ascending Dose (MAD- Arm B); An expansion cohort (upto 4 cohorts) will be enrolled after maximum tolerated dose or recommended phase 2 dose is established.	Drug: TNB-738; TNB-738 is an investigation drug. Other: Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of TNB-738 by the incidence of treatment emergent adverse events in Single Ascending group. Adverse Events will be graded according to the NCI-CTCAE, version 5.0	13 weeks
Safety and tolerability of TNB-738 by the incidence of treatment emergent adverse events in Multiple Ascending group. Adverse Events will be graded according to the NCI-CTCAE, version 5.0	21 weeks
To investigate the Cmax (maximum Serum concentration) of TNB-738 following Single Ascending Dose.	13 weeks
To investigate the Cmax (Maximum Serum concentration) of TNB-738 following Multiple Ascending Dose	21 weeks
Tmax (time for maximum serum concentration) for Single Ascending Dose	13 weeks
Tmax (time for maximum serum concentration) for Multiple Ascending Dose	21 weeks
Terminal elimination half-life (t1/2) for Single Ascending Dose	13 weeks
Terminal elimination half-life (t1/2) for Multiple Ascending Dose	21 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Anti drug antibodies (ADA) as a measurement of immunogenicity following Single Ascending Dose of TNB-738	13 weeks
Anti drug antibodies (ADA) as a measurement of immunogenicity following Multiple Ascending Dose of TNB-738	21 weeks
To determine CD38 enzyme activity following Single Ascending Dose	13 weeks
To determine CD38 enzyme activity following Multiple Ascending Dose	21 weeks

Collaborators and Investigators

• Sponsor: TeneoFour Inc.
• Collaborators: Novotech (Australia) Pty Limited
• Investigators: Study Director: Ben Buelow, MD, PhD, TeneoFour Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2022
• Primary Completion (Actual): May 4, 2023
• Study Completion (Actual): July 11, 2023

Study Registration Dates

• First Submitted: November 23, 2021
• First Submitted That Met QC Criteria: January 18, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: CD38
• Other Study ID Numbers: TNB-738

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
• product manufactured in and exported from the U.S.: Yes