Study to Evaluate Safety and Efficacy in Adult Subjects With ITP

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of BMS-986004 when administered in subjects with ITP.

Official Title
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Open Label, Adaptive Design, Ascending, Multiple-Dose Study to Evaluate Safety and Efficacy of BMS-986004 in Adult Subjects With Primary Immune Thrombocytopenia (ITP)

Conditions
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Immune Thrombocytopenic Purpura

Intervention / Treatment
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* Drug: BMS-986004 75 mg IV
* Drug: BMS-986004 225 mg IV
* Drug: BMS-986004 675 mg IV
* Drug: BMS-986004 1500 mg IV


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: ≥18 years old, diagnosed with persistent or chronic ITP Exclusion Criteria: Secondary immune thrombocytopenia Drug induced thrombocytopenia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: BMS-986004<br>BMS-986004 solution intravenously (IV) as specified | Drug: BMS-986004 75 mg IV<br>* BMS-986004 (75 mg) infusion (50 ml) administered in 120 minutes<br>|
| Experimental: Arm B: BMS-986004<br>BMS-986004 solution intravenously as specified | Drug: BMS-986004 225 mg IV<br>* BMS-986004 (225 mg) infusion (100 ml) administered in 120 minutes<br>|
| Experimental: Arm C: BMS-986004<br>BMS-986004 solution intravenously as specified | Drug: BMS-986004 675 mg IV<br>* BMS-986004 (675 mg) infusion (100 ml) administered in 120 minutes<br>|
| Experimental: Arm D: BMS-986004<br>BMS-986004 solution intravenously as specified | Drug: BMS-986004 1500 mg IV<br>* BMS-986004 (1500 mg) infusion (100 ml) administered in 120 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term | The primary objective to establish safety was measured by the primary endpoints of AEs and SAEs for both Short term and Long term periods | Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term) | 
| Number of ECG Abnormalities | The primary objective to establish safety was measured by investigator identified Electrocardiogram Abnormalities for both Short term and Long term periods. ECG parameters included heart rate, PR interval, QRS interval, and QTcF interval (QT interval corrected for heart rate) | Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term) | 
| Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) | D-dimer and thrombin antithrombin (TAT) in plasma were quantified as measures of thromboembolism risk. D-dimer was evaluated by Enzyme linked immune sorbent assay (ELISA) method (D-dimer reference range 0-0.63 micrograms/milliliters fibrinogen equivalent units [mcg/ml FEU]). TAT reference range 0-4.1 ng/ml. | Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long Term) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (RR) of BMS-986004: Short Term and Long Term | Overall Response Rate (ORR) was defined as the proportion of participants who achieved a complete response (CR) or response (R). CR was defined as platelet count ≥ 100,000/mm3 and absence of bleeding. R was defined as platelet count ≥ 30,000/mm3 and at least 2-fold increase from the baseline count and absence of bleeding. | Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term) | 
| Maximum Observed Serum Concentration (Cmax) of BMS-986004 | Pharmacokinetic parameter (Cmax) of BMS-986004, derived from serum concentration versus time. who have adequate PK profiles. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) | 
| Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 | Pharmacokinetics of BMS-986004 were derived from serum concentration versus time data. AUC(TAU) = Area under the concentration-time curve in one dosing interval. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) | 
| Trough Observed Serum Concentration (Ctrough) of BMS-986004 | Pharmacokinetics of BMS-986004 were derived from serum concentration versus time data. Ctrough = Trough observed serum concentration. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) | 
| Total Body Clearance (CLT) of BMS-986004 | Pharmacokinetics of BMS-986004 were derived from serum concentration versus time data. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) | 
| AUC Accumulation Index (AI_AUC) of BMS-986004 | AUC accumulation index (AI_AUC) = ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose of BMS-986004. On study Day 57, non-responders in each treatment group other than the 1500 mg group were dose escalated to the starting dose of the next higher treatment group. | Day 1 (0 hour [h], 2h, 24h, 72h, 168h), Day 15 (0h), Day 29 (0h), Day 43 (0h, 168h), Day 57 (0h, 2h), Day 71 (0h, 2h, 24h, 96h, 168h), Day 85 (0h, 336h, 672h, 1008h, 1344h) |