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

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

Detailed Description
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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.

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

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: TNB-738
* Drug: TNB-738


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female Age 18 - 75 Body mass index (BMI) ranging between 18 and 35 kg/m2, inclusive Female subjects of child-bearing potential must agree to use one of the study-approved effective contraceptive methods for the duration of the study Male subjects must practice true abstinence or agree to use a condom while participating in the study through End of study (EOS) If female, a negative serum pregnancy test at Screening and urinary pregnancy test at Day -1 is required Able to read, understand, and provide signed informed consent Able to communicate adequately with the investigator and to comply with the requirements for the entire study. Exclusion Criteria: Subject has any significant medical condition that would prevent the subject from participating in the study. Subject is pregnant or breastfeeding. Subject is currently receiving treatment with a biologic agent. Subject has a history of anaphylactic reactions to biologic agents. Subject has been dosed with another investigational drug study within 60 days prior to study drug administration. Subject has current or recent (within 4 weeks prior to screening) signs or symptoms of infection that require antibiotic administration. 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. 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. Subject has a positive urine drug test or alcohol breath test at screening. 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. Subject is HIV, HBV, or HCV positive. Subject has received a live virus vaccine within 4 weeks of dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose (SAD -Arm A)<br>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<br>* TNB-738 is an investigation drug. Other: Matching placebo<br>|
| Experimental: Multiple Ascending Dose (MAD- Arm B)<br>An expansion cohort (upto 4 cohorts) will be enrolled after maximum tolerated dose or recommended phase 2 dose is established. | Drug: TNB-738<br>* TNB-738 is an investigation drug. Other: Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD38