A Study to Evaluate the Safety and Pharmacokinetics of BX-001N in Healthy Participants

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, single and multiple ascending dose, Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of BX-001N after intravenous administration in approximately 64 healthy participants

Detailed Description
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This study comprises of 2 parts: Part 1- Single Ascending Dose (SAD)- This part will enroll approximately 40 participants across 5 cohorts where each participant will receive a single intravenous (IV) bolus dose in healthy participants. On Day 1, participants in each cohort will receive investigational product (IP) (i.e., BX-001N or Placebo) as a single IV bolus following a minimum 8-hour fast. Part 2 -Multiple Ascending Dose (MAD)- This part will enroll approximately 24 participants across 3 cohorts where each participants will receive intravenous (IV) bolus dose for 7 sequential daily. At the same time each morning from Day 1 to Day 7 (inclusive), participants in each cohort will receive IP (i.e., BX-001N or Placebo) as a single IV bolus following a minimum 8-hour fast.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BX-001N After Intravenous Administration in Healthy Participants

Conditions
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Ischemia-reperfusion Injury

Intervention / Treatment
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* Drug: BX-001N Part 1
* Drug: BX-001N Part 2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 50 years of age In good general health at Screening and/or before the first administration of IP BMI > 18.0 and < 32.0 kg/m2 at Screening Nonsmoker and must not have used any tobacco products within 2 months prior to screening Females must not be pregnant or lactating, and females and males must use acceptable, highly effective double contraception during study and follow-up period Person who can provide written informed consent prior to the commencement of all study procedures Exclusion Criteria: Underlying physical or psychological medical condition to comply with the protocol or complete the study per protocol Genetic disorder with severe and abnormal bilirubin metabolism Blood or plasma donation or significant blood loss prior to the first administration of IP Viral or bacterial infection prior to the first administration of IP Poor venous access Significant scarring or tattoos at the planned site of IP administration History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents History or active cardiovascular, respiratory, kidney, endocrine, blood, digestive, central nervous, urinary and/or musculoskeletal disease History of malignancy prior to Screening Abnormal ECG findings History or presence of a condition associated with significant immunosuppression History of life-threatening infection Infections requiring parenteral antibiotics Vaccination prior to the first administration of IP Exposure to any significantly immune suppressing drug Abnormal vital signs findings Abnormal laboratory findings Positive results for viral testing at Screening Positive result at Screening and Day -1 for toxicology screening panel History of substance abuse or dependency or history of recreational intravenous (IV) drug use Excess of regular alcohol consumption Use of any IP or investigational medical device within 30 days prior to Screening Unable to adhere to the prohibited therapies Unwilling to adhere to the dietary restrictions Unwilling to refrain from strenuous exercise

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BX-001N Part 1<br>Part 1 is SAD with 5 cohorts where each participant will receive single IV bolus following a 8hr fast. | Drug: BX-001N Part 1<br>* Dosage form- IV bolus Dosage- In the five cohorts, each participant receives a single IV bolus administration in one of the five doses based on body weight and followed up for 7 days.<br>|
| Experimental: BX-001N Part 2<br>Part 2 is MAD with 3 cohorts where each participant will receive 7 sequential daily IV bolus doses following a 8hr fast. | Drug: BX-001N Part 2<br>* Dosage form- IV bolus Dosage- In the three cohorts, each participant receives a single IV bolus administration for 7 sequential days in one of the three doses based on body weight and followed up for 14 days.<br>|
| Placebo Comparator: Placebo<br>Matching doses of placebo | Drug: Placebo<br>* Participants will receive matching placebo across Part 1 and 2 of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Treatment emergent Adverse events (TEAEs) | TEAE will be collected to assess participants' safety after BX-001N treatment | SAD-Screening to Day 7; MAD- Screening to Day 14 | 
| Number of participants with clinical laboratory abnormalities |  | SAD-Screening to Day 7; MAD- Screening to Day 14 | 
| Number of participants with changes in the 12-lead electrocardiogram (ECG) |  | SAD-Screening to Day 7; MAD- Screening to Day 14 | 
| Number of incidences of injection site reactions |  | SAD-Day 1 to Day 2; MAD- Day 1 to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Cmax (maximum Concentration) of BX-001N with 5 different doses of SAD and 3 different doses of MAD | SAD's samples of PK are collected at total 12 time points from pre-dose and up to Day 3 after dosing. MAD's samples of PK are collected at total 26 time points from pre-dose and up to Day 8 after dosing. | SAD- Day 1 to Day 3; MAD- Day 1 to Day 8 | 
| Changes in Tmax (Time of maximum Concentration) of BX-001N with 5 different doses of SAD and 3 different doses of MAD | SAD's samples of PK are collected at total 12 time points from pre-dose and up to Day 3 after dosing. MAD's samples of PK are collected at total 26 time points from pre-dose and up to Day 8 after dosing | SAD- Day 1 to Day 3; MAD- Day 1 to Day 8 | 
| Changes in AUC (area under curve) of BX-001N with 5 different doses of SAD and 3 different doses of MAD | SAD's samples of PK are collected at total 12 time points from pre-dose and up to Day 3 after dosing. MAD's samples of PK are collected at total 26 time points from pre-dose and up to Day 8 after dosing. | SAD- Day 1 to Day 3; MAD- Day 1 to Day 8 | 
| Change in Immunogenicity- Incidence of Anti-drug antibody (ADA) by polyethylene glycol (PEG) | Up to 3 samples will be collected in total and additional samples if positive results | SAD-Day 1 to Day 7; MAD- Day 1 to Day 14 | 
| Change in Immunogenicity- Titers of Anti-drug antibody (ADA) by polyethylene glycol (PEG) | Up to 3 samples will be collected in total and additional samples if positive results | SAD-Day 1 to Day 7; MAD- Day 1 to Day 14 | 
| Change in Immunogenicity- Duration of Anti-drug antibody (ADA) by polyethylene glycol (PEG) | Up to 3 samples will be collected in total and additional samples if positive results | SAD-Day 1 to Day 7; MAD- Day 1 to Day 14 |