Study to Evaluate the Safety, Tolerability, PK, and PD of BMS-986090 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-986090 in healthy subjects.

Official Title
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Double-Blinded, Randomized, Placebo-Controlled, Single Ascending Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986090 in Healthy Subjects

Conditions
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Healthy Adult Volunteers

Intervention / Treatment
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* Drug: BMS-986090
* Drug: Placebo matching with BMS-986090
* Drug: Keyhole limpet hemocyanin


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Healthy male and female (of not childbearing potential), ages 18-45 years, inclusive BMI 18 to 32 kg/m2, inclusive Exclusion Criteria: - Any significant acute or chronic medical illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel 1: BMS-986090 (0.5 mg) or Placebo<br>BMS-986090 0.5 mg solution single dose subcutaneously once OR Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once | Drug: BMS-986090<br> <br> Drug: Placebo matching with BMS-986090<br> <br> |
| Experimental: Panel 2: BMS-986090 (3 mg) or Placebo<br>BMS-986090 3 mg solution single dose subcutaneously once OR Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once | Drug: BMS-986090<br> <br> Drug: Placebo matching with BMS-986090<br> <br> |
| Experimental: Panel 3: BMS-986090 (10 mg) or Placebo<br>BMS-986090 10 mg solution single dose subcutaneously once OR Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once | Drug: BMS-986090<br> <br> Drug: Placebo matching with BMS-986090<br> <br> |
| Experimental: Panel 4: BMS-986090 (30 mg) or Placebo + KLH (1 mg)<br>BMS-986090 30 mg solution single dose subcutaneously once OR Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once And Keyhole limpet hemocyanin (KLH) 1 mg solution single intramuscular dose once | Drug: BMS-986090<br> <br> Drug: Placebo matching with BMS-986090<br> <br> Drug: Keyhole limpet hemocyanin<br> <br> * Other names: KLH;|
| Experimental: Panel 5: BMS-986090 (100 mg) or Placebo + KLH (1 mg)<br>BMS-986090 100 mg solution single dose subcutaneously once OR Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once And KLH 1 mg solution single intramuscular dose once | Drug: BMS-986090<br> <br> Drug: Placebo matching with BMS-986090<br> <br> Drug: Keyhole limpet hemocyanin<br> <br> * Other names: KLH;|
| Experimental: Panel 6: BMS-986090 (100 mg) or Placebo<br>BMS-986090 100 mg solution single dose intravenously once OR Placebo matching with BMS-986090 0 mg solution single dose intravenously once | Drug: BMS-986090<br> <br> Drug: Placebo matching with BMS-986090<br> <br> |
| Experimental: Panel 7: BMS-986090 (300 mg) or Placebo + KLH (1 mg)<br>BMS-986090 300 mg solution single dose subcutaneously once OR Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once And KLH 1 mg solution single intramuscular dose once | Drug: BMS-986090<br> <br> Drug: Placebo matching with BMS-986090<br> <br> Drug: Keyhole limpet hemocyanin<br> <br> * Other names: KLH;|
| Experimental: Panel 8: BMS-986090 (750 mg) or Placebo<br>BMS-986090 750 mg solution single dose intravenously once OR Placebo matching with BMS-986090 0 mg solution single dose intravenously once | Drug: BMS-986090<br> <br> Drug: Placebo matching with BMS-986090<br> <br> |
| Experimental: Panel 9: BMS-986090 (150 mg) or Placebo<br>BMS-986090 150 mg solution subcutaneously once weekly for 4 weeks OR Placebo matching with BMS-986090 0 mg solution subcutaneously once weekly for 4 weeks | Drug: BMS-986090<br> <br> Drug: Placebo matching with BMS-986090<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of single dose measured by incidence, potential significance and clinical importance of AEs, as determined by medical review of AE reports, vital sign measurements, ECGs and results of physical examination and laboratory tests | AE = Adverse event ECG = Electrocardiogram | Up to Day 85 after single dose of BMS-986090 | 
| Safety and tolerability of multiple dose measured by incidence, potential significance and clinical importance of AEs, as determined by medical review of AE reports, vital sign measurements, ECGs and results of physical examination and laboratory tests |  | Up to Day 106 after multiple dose of BMS-986090 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) of BMS-986090 single dose subcutaneous (SC) and intravenous (IV) |  | Days 1 -85 | 
| Time of maximum observed serum concentration (Tmax) of single dose BMS-986090 SC and IV |  | Days 1 -85 | 
| Area under the serum concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of single dose BMS-986090 SC and IV |  | Days 1 -85 | 
| Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of single dose BMS-986090 SC and IV |  | Days 1 -85 | 
| Terminal serum half-life (T-HALF) of single dose BMS-986090 SC and IV |  | Days 1 -85 | 
| Total body clearance (CLT) of single dose BMS-986090 IV |  | Days 1 -85 | 
| Apparent total body clearance (CLT/F) of single dose BMS-986090 SC |  | Days 1 -85 | 
| Volume of distribution at terminal phase (Vz) of single dose BMS-986090 IV |  | Days 1 -85 | 
| Volume of distribution during steady state (Vss) of single dose BMS-986090 IV |  | Days 1 -85 | 
| Apparent volume of distribution at terminal phase (Vz/F) of single dose BMS-986090 SC |  | Days 1 -85 | 
| Absolute bioavailability (F) of single dose BMS-986090 SC |  | Days 1 -85 | 
| Maximum observed serum concentration (Cmax) of multiple dose BMS-986090 SC |  | Days 1 -106 | 
| Time of maximum observed serum concentration (Tmax) of multiple dose BMS-986090 SC |  | Days 1 -106 | 
| Terminal serum half-life (T-HALF) of multiple dose BMS-986090 SC |  | Days 1 -106 | 
| Area under the serum concentration-time curve in one dosing Interval [AUC(TAU)] of multiple dose BMS-986090 SC |  | Days 1 -106 | 
| Trough observed plasma concentration (Ctrough) of multiple dose BMS-986090 SC |  | Days 1 -106 | 
| Average concentration over a dosing interval (Css-avg) of multiple dose BMS-986090 SC |  | Days 1 -106 | 
| Degree of Fluctuation (DF) of multiple dose BMS-986090 SC |  | Days 1 -106 | 
| AUC accumulation index (AI_AUC); ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose of BMS-986090 SC (multiple dose) |  | Days 1 -106 | 
| Cmax accumulation index (AI_Cmax); ratio of Cmax at steady state to Cmax after the first dose of BMS-986090 SC (multiple dose) |  | Days 1 -106 | 
| Apparent total body clearance (CLT/F) of multiple dose BMS-986090 SC |  | Days 1 -106 | 
| Anti-KLH immunoglobulin G (IgG) and IgM antibody levels of single dose BMS-986090 SC |  | Days 1 -85 | 
| Immunogenicity of BMS-986090 following single SC / IV infusion measured by frequency of subjects with positive anti-drug-antibody (ADA) assessment and frequency of subjects who develop positive ADA following a negative baseline |  | Days 1 -85 | 
| Receptor occupancy (RO) of BMS-986090 following single SC or IV infusion |  | Days 1 -85 |