Study to Evaluate Safety and Efficacy in Adult Subjects With ITP

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02273960
• Collaborator: (none)
• Enrollment: 46
• Locations: 20
• Arms: 4
• Actual Duration (Months): 38.2
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Immune Thrombocytopenic Purpura	Drug: BMS-986004 75 mg IV; Drug: BMS-986004 225 mg IV; Drug: BMS-986004 675 mg IV; Drug: BMS-986004 1500 mg IV	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label, Adaptive Design, Ascending, Multiple-Dose Study to Evaluate Safety and Efficacy of BMS-986004 in Adult Subjects With Primary Immune Thrombocytopenia (ITP)
• Actual Study Start Date: Nov 17, 2014
• Actual Primary Completion Date: Jan 22, 2018
• Actual Study Completion Date: Jan 22, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term [Day 1 to Day 141 (Short term) and Day 1 to Day 398 (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

2. Number of ECG Abnormalities [Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term)]

   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)

3. Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT) [Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long Term)]

   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.

Secondary Outcome Measures

1. Response Rate (RR) of BMS-986004: Short Term and Long Term [Day 1 to Day 141 (Short term) and Day 1 to Day 398 (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.

2. Maximum Observed Serum Concentration (Cmax) of BMS-986004 [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)]

   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.

3. Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004 [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)]

   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.

4. Trough Observed Serum Concentration (Ctrough) of BMS-986004 [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)]

   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.

5. Total Body Clearance (CLT) of BMS-986004 [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)]

   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.

6. AUC Accumulation Index (AI_AUC) of BMS-986004 [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) = 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ. Of Southern Calif. /Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
3	Emory University	Atlanta	Georgia	United States	30322
4	Columbus Regional Research Institute	Columbus	Georgia	United States	31904
5	Mass General Hospital	Boston	Massachusetts	United States	02114
6	Rutgers- Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
7	Local Institution	Randwick	New South Wales	Australia	2031
8	Local Institution	Brisbane	Queensland	Australia	4102
9	Hamilton Health Sciences/Mc Master Univ Med Ctre	Hamilton	Ontario	Canada	L8S 4K1
10	Local Institution	Tbilisi		Georgia	0112
11	Local Institution	Chisinau		Moldova, Republic of	MD 2025
12	Oddzial Kliniczny Hematologii i Profilaktyki Chorob Nowotworowych	Chorzow		Poland	41-500
13	Specjalistyczny Gabinet Lekarski Prof. dr hab. Krzysztof Giannopoulos	Lublin		Poland	20-601
14	Local Institution	Warszawa		Poland	02-106
15	Local Institution	Saint-Petersburg		Russian Federation	194356
16	Local Institution	Smolensk		Russian Federation
17	Local Institution	London	Greater London	United Kingdom	NW1 2PG
18	Local Institution	Manchester	Greater Manchester	United Kingdom	M13 9WL
19	Local Institution	Glasgow	Lanarkshire	United Kingdom	G4 OSF
20	Local Institution	London		United Kingdom	E1 1BB

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol - Aug 8, 2016
• Statistical Analysis Plan - Jan 14, 2015

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02273960
• Other Study ID Numbers: IM140-103; 2014-001429-33
• First Posted: Oct 24, 2014
• Last Update Posted: Jul 16, 2019
• Last Verified: Jul 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic

Study Results

Participant Flow

Pre-assignment Detail	46 participants were enrolled in the study and 26 participants entered the treatment period. Of the 20 who did not enter the treatment period, 19 did not meet study criteria and 1 experienced an adverse event.

Arm/Group Title	BMS-986004 75mg IV	BMS-986004 225mg IV	BMS-986004 675 mg IV	BM-986004 1500 mg IV
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Period Title: Short Term Period
STARTED	5	6	5	10
COMPLETED	0	0	1	4
NOT COMPLETED	5	6	4	6
Period Title: Short Term Period
STARTED	0	0	1	4
COMPLETED	0	0	1	3
NOT COMPLETED	0	0	0	1

Baseline Characteristics

Arm/Group Title	BMS 75 mg	BMS-986004 225mg IV	BMS 675mg	BMS 1500mg	Total
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg	Total of all reporting groups
Overall Participants	5	6	5	10	26
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.8 (20.58)	43.2 (16.33)	34.2 (16.93)	55.3 (16.09)	48.0 (18.16)
Sex: Female, Male (Count of Participants)
Female	2 40%	2 33.3%	4 80%	4 40%	12 46.2%
Male	3 60%	4 66.7%	1 20%	6 60%	14 53.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 20%	4 66.7%	4 80%	8 80%	17 65.4%
Unknown or Not Reported	4 80%	2 33.3%	1 20%	2 20%	9 34.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 16.7%	0 0%	1 10%	2 7.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	1 10%	1 3.8%
White	4 80%	5 83.3%	5 100%	7 70%	21 80.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 20%	0 0%	0 0%	1 10%	2 7.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Short Term and Long Term
Description	The primary objective to establish safety was measured by the primary endpoints of AEs and SAEs for both Short term and Long term periods
Time Frame	Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term)

Outcome Measure Data

Analysis Population Description

All participants who had received at least 1 dose of study treatment

Arm/Group Title	BMS 75 mg	BMS 225 mg	BMS-986004 675 mg IV	BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Measure Participants	5	6	5	10
Number of participants with AEs	1 20%	5 83.3%	5 100%	9 90%
Number of participants with SAEs	0 0%	0 0%	1 20%	1 10%

2. Primary Outcome

Title	Number of ECG Abnormalities
Description	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)
Time Frame	Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term)

Outcome Measure Data

Analysis Population Description

All participants who had received at least 1 dose of study treatment

Arm/Group Title	BMS 75 mg	BMS 225 mg	BMS-986004 675 mg IV	BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Measure Participants	5	6	5	10
Screening	1	3	2	3
Day 1	1	2	2	3
Day 71	0	2	0	0
Day 72	1	0	1	1
End of Treatment	1	3	2	1
LTE Day 1	0	0	0	2
LTE Day 71	0	0	0	2
End of LTE	0	0	0	1

3. Primary Outcome

Title	Number of Laboratory Abnormalities of Safety Biomarkers: d-Dimer and Thrombin Anti-Thrombin (TAT)
Description	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.
Time Frame	Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long Term)

Outcome Measure Data

Analysis Population Description

All participants who had received at least 1 dose of study treatment

Arm/Group Title	BMS 75 mg	BMS 225 mg	BMS-986004 675 mg IV	BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Measure Participants	5	6	5	10
# of events: d-Dimer, Normal	56	81	60	106
# of events: d-Dimer, High	12	14	15	17
# of events: TAT Complex, Normal	52	71	46	112
# of events: TAT Complex, High	21	30	31	28

4. Secondary Outcome

Title	Response Rate (RR) of BMS-986004: Short Term and Long Term
Description	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.
Time Frame	Day 1 to Day 141 (Short term) and Day 1 to Day 398 (Long term)

Outcome Measure Data

Analysis Population Description

All participants who had received at least 1 dose of study treatment

Arm/Group Title	BMS 75 mg	BMS 225 mg	BMS-986004 675 mg IV	BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Measure Participants	5	6	5	10
RR during ST	0.2 4%	0.3 5%	0.4 8%	0.4 4%
RR during LTE	0 0%	0 0%

5. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of BMS-986004
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Evaluable PK population defined as participants with adequate PK profiles. The number of analyzed participants in each arm at specified time points represent the actual number of subjects evaluated after intra-participant dose escalation once the participant had completed the response phase of the study.

Arm/Group Title	BMS 75 mg	BMS 225 mg	BMS-986004 675 mg IV	BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Measure Participants	2	6	6	13
Cmax Day 1	19353.5 (6131.32)	59478.8 (10021.04)	177706.3 (37924.30)	296561.9 (119530.86)
Cmax Day 71	62469.8 (27336.64)	186981.0 (22216.82)	373588.9 (89833.77)

6. Secondary Outcome

Title	Area Under the Concentration-time Curve in One Dosing Interval [AUC(TAU)] of BMS-986004
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Evaluable PK Population. The number of analyzed participants in each arm at specified time points represent the actual number of subjects evaluated after intra-participant dose escalation once the participant had completed the response phase of the study.

Arm/Group Title	BMS 75 mg	BMS 225 mg	BMS-986004 675 mg IV	BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Measure Participants	2	6	6	13
AUC(TAU) Day 1	915500 (196460)	3445000 (708290)	11440000 (3041300)	18370000 (7351000)
AUC(TAU) Day 71	4408000 (3313000)	11460000 (2124900)	26500000 (9366800)

7. Secondary Outcome

Title	Trough Observed Serum Concentration (Ctrough) of BMS-986004
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Evaluable PK Population. The number of analyzed participants in each arm at specified time points represent the actual number of subjects evaluated after intra-participant dose escalation once the participant had completed the response phase of the study.

Arm/Group Title	BMS 75 mg	BMS 225 mg	BMS-986004 675 mg IV	BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Measure Participants	5	6	6	14
Ctrough, Day 15	978.0 (1080.82)	2373.0 (1182.00)	7556.4 (1952.53)	15282.5 (9710.77)
Ctrough, Day 29	1011.4 (999.13)	3157.7 (1458.85)	10236.0 (3737.42)	21353.6 (14144.90)
Ctrough, Day 43	1207.0 (852.88)	3527.7 (1576.34)	9416.2 (4410.57)	19105.3 (14980.50)
Ctrough, Day 57	25339.5 (49053.16)	3360.5 (1082.75)	20553.1 (19099.39)
Ctrough, Day 71	3466.0 (3209.75)	8347.7 (3215.32)	25057.3 (18007.59)
Ctrough, Day 85	4018.8 (4099.35)	9075.7 (4268.76)	24308.9 (19213.61)

8. Secondary Outcome

Title	Total Body Clearance (CLT) of BMS-986004
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Evaluable PK Population. The number of analyzed participants in each arm at specified time points represent the actual number of subjects evaluated after intra-participant dose escalation once the participant had completed the response phase of the study.

Arm/Group Title	BMS 75 mg	BMS 225 mg	BMS-986004 675 mg IV	BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Measure Participants	2	6	6	13
CLT Day 1	0.0789 (0.01514)	0.0618 (0.01617)	0.0561 (0.01395)	0.0860 (0.03037)
CLT Day 71	0.0716 (0.04106)	0.0611 (0.01449)	0.0628 (0.02061)

9. Secondary Outcome

Title	AUC Accumulation Index (AI_AUC) of BMS-986004
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Evaluable PK Population. Only participants with adequate PK profiles were included in the summary statistics; "0" participants analyzed indicates "no data were available for that cohort for this Summary Statistic"

Arm/Group Title	BMS 75 mg	BMS 225 mg	BMS-986004 675 mg IV	BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg	BMS-986004 dose level 225 mg	BMS-986004 dose level 675 mg	BMS-986004 dose level 1500 mg
Measure Participants	0	0	0	12
Mean (Standard Deviation) [Ratio]	1.7996 (0.597881)

Adverse Events

Time Frame	All SAEs were collected that occurred during 21 day screening period, a 12 week treatment period (6 weeks of response Phase and 6 weeks of remission phase) and a 1 month follow up period. The collection of nonserious AE information began at initiation of study drug and up to follow up.
Arm/Group Title	BMS-986004 75mg IV		BMS-986004 225mg IV		BMS 675mg		BMS 1500mg
Arm/Group Description	BMS-986004 dose level 75 mg		BMS-986004 dose level 225 mg		BMS-986004 dose level 675 mg		BMS-986004 dose level 1500 mg
All Cause Mortality
	BMS-986004 75mg IV		BMS-986004 225mg IV		BMS 675mg		BMS 1500mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Serious Adverse Events
	BMS-986004 75mg IV		BMS-986004 225mg IV		BMS 675mg		BMS 1500mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)		2/5 (40%)		1/10 (10%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Nervous system disorders
Haemorrhage intracranial	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	BMS-986004 75mg IV		BMS-986004 225mg IV		BMS 675mg		BMS 1500mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		5/6 (83.3%)		5/5 (100%)		9/10 (90%)
Blood and lymphatic system disorders
Anaemia	0/5 (0%)		1/6 (16.7%)		2/5 (40%)		1/10 (10%)
Microcytic anaemia	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Cardiac disorders
Tachycardia	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Gastrointestinal disorders
Abdominal pain	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Diarrhoea	0/5 (0%)		0/6 (0%)		1/5 (20%)		1/10 (10%)
Faeces discoloured	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Gingival bleeding	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Haemorrhoidal haemorrhage	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Mouth haemorrhage	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Mouth ulceration	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Nausea	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Stomatitis	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
General disorders
Fatigue	0/5 (0%)		0/6 (0%)		0/5 (0%)		4/10 (40%)
Feeling cold	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Infusion site bruising	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Injection site reaction	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Peripheral swelling	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Pyrexia	1/5 (20%)		0/6 (0%)		0/5 (0%)		0/10 (0%)
Immune system disorders
Allergy to animal	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Infections and infestations
Gastroenteritis	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Lower respiratory tract infection	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Periodontitis	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Pharyngitis	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Phlebitis infective	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Respiratory tract infection viral	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Upper respiratory tract infection	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Urinary tract infection	1/5 (20%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Viral upper respiratory tract infection	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Injury, poisoning and procedural complications
Fall	0/5 (0%)		0/6 (0%)		0/5 (0%)		2/10 (20%)
Investigations
Alanine aminotransferase increased	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Aspartate aminotransferase increased	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Blood creatine phosphokinase increased	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Heart sounds abnormal	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Platelet count decreased	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Platelet count increased	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Weight decreased	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Metabolism and nutrition disorders
Hyperglycaemia	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Hypokalaemia	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Hypophosphataemia	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Steroid diabetes	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		1/10 (10%)
Arthritis	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		1/10 (10%)
Back pain	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Muscular weakness	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		1/10 (10%)
Musculoskeletal pain	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Osteoporosis	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Pain in extremity	0/5 (0%)		0/6 (0%)		1/5 (20%)		2/10 (20%)
Nervous system disorders
Dizziness	1/5 (20%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Headache	1/5 (20%)		1/6 (16.7%)		1/5 (20%)		0/10 (0%)
Migraine	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Psychiatric disorders
Neurosis	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Stress	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Renal and urinary disorders
Micturition urgency	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	0/5 (0%)		0/6 (0%)		1/5 (20%)		1/10 (10%)
Dyspnoea	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Nasal congestion	0/5 (0%)		3/6 (50%)		0/5 (0%)		0/10 (0%)
Oropharyngeal pain	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Pharyngeal haemorrhage	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Productive cough	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Petechiae	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Purpura	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/10 (0%)
Urticaria	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/10 (0%)
Social circumstances
Exercise lack of	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Vascular disorders
Flushing	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)
Peripheral coldness	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/10 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.