Open-label Safety and PK Study of BION-1301 in Japanese Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
Phase 1, open-label study designed to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic of multiple doses of BION-1301 in Japanese healthy subjects.

Detailed Description
-----------------
This is a Phase 1 study of BION-1301, a first-in-class humanized IgG4 anti-a proliferation-inducing ligand (APRIL) monoclonal antibody. This is a single-center, open-label study designed to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic of a single subcutaneous dose of BION-1301 in Japanese healthy subjects in 3 dose level cohorts. The study will enroll up to 36 Japanese subjects across 3 dose level cohorts.

Official Title
-----------------
BION-1301 - A Phase 1, Open-label, Single Subcutaneous Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Japanese Healthy Subjects

Conditions
-----------------
Healthy Volunteer

Intervention / Treatment
-----------------
* Drug: BION-1301


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: First generation Japanese (confirmed at screening). The definition of first generation is the subject, the subject's biological parents, and the subject's biological grandparents are of exclusively Japanese origin and were born in Japan. Body mass index (BMI) between 18 and 30 kg/m^2, inclusive, at screening with a weight of at least 47 kg. In good health, as determined by medical history, physical examination, vital signs assessment, 12-lead ECG, and clinical laboratory evaluations within normal reference ranges or outside of normal reference ranges considered not clinically relevant by the investigator Female subjects of childbearing potential must have a negative urine or serum pregnancy test, must agree to try to not become pregnant, must agree to consistently use highly effective contraceptive methods, and must agree not to breastfeed or donate ova for a period as defined in the study protocol. Male subjects must agree to use highly effective contraceptive methods and must not donate sperm for a period as defined in the study protocol. Exclusion Criteria: Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee). History of malignancy during the last 3 years; exceptions include adequately treated basal cell carcinoma and squamous cell carcinoma of the skin Confirmed systolic blood pressure >140 or <90 mmHg, diastolic blood pressure >90 or <50 mmHg, and pulse rate >100 or <40 beats per minute at either screening or predose on Day 1. Received a live (attenuated) vaccine(s) within 3 months prior to check-in and/or a vaccine(s) that do not contain live microorganism(s) within 14 days prior to check-in. Have previously completed or withdrawn from this study or any other study investigating BION-1301, and have previously received BION-1301. Positive urine drug screen, alcohol test, or cotinine test at screening or check-in.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single ascending dose study in Japanese healthy subjects
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>A single dose of BION-1301 will be administered subcutaneously on Day 1 at dose level A | Drug: BION-1301<br>* A solution for SC injection administered as a single dose<br>|
| Experimental: Cohort B<br>A single dose of BION-1301 will be administered subcutaneously on Day 1 at dose level B | Drug: BION-1301<br>* A solution for SC injection administered as a single dose<br>|
| Experimental: Cohort C<br>A single dose of BION-1301 will be administered subcutaneously on Day 1 at dose level C | Drug: BION-1301<br>* A solution for SC injection administered as a single dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of BION-1301 | Number of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs); changes from baseline in safety parameters; and number of subjects with injection site reactions | Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics-Cmax | Maximum plasma concentration | Day 85 | 
| Pharmacokinetics-Tmax | Time at which the maximum plasma concentration (Cmax) occurs | Day 85 | 
| Pharmacokinetics-AUC∞ | Area under the plasma concentration-time curve from dosing (time zero) extrapolated to infinity | Day 85 | 
| Pharmacokinetics-AUClast | Area under the plasma concentration-time curve from dosing (time zero) to the time of the last measured concentration | Day 85 | 
| Pharmacokinetics-t1/2 | Time required for the drug concentration to decrease by a factor of one-half in the terminal phase | Day 85 | 
| Pharmacokinetics-CL/F | Serum concentration after single dose will be measured and the apparent oral clearance will be calculated | Day 85 | 
| Pharmacokinetics-Vz/F | Serum concentration after single dose will be measured and the apparent volume of distribution will be calculated | Day 85 | 
| The effect of BION-1301 on pharmacodynamic (PD) parameters | Changes in immunoglobulin levels (IgA, IgG, and IgM) | Day 85 | 
| The levels of anti-drug antibodies | Blood anti-drug antibodies (ADA) and neutralizing antibody (NAb) levels | Day 85 |