A Study to Evaluate the Pharmacokinetics of Abatacept Converted From Drug Substance by Two Different Processes

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03714022
• Collaborator: (none)
• Enrollment: 140
• Locations: 2
• Arms: 2
• Actual Duration (Months): 4.7
• Patients Per Site: 70
• Patients Per Site Per Month: 14.8

Study Details

Study Description

Brief Summary

The main objective of this study is to compare the pharmacokinetics (PK) of the abatacept drug product converted from drug substance by a new drug substance process (Treatment A) relative to the current drug substance process (Treatment B) following a single dose (750 mg) intravenous (IV) infusion in healthy participants.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Abatacept	Phase 1

Detailed Description

Participants will be admitted to the clinical facility the day prior to dosing (Day -1) and will be confined until at least 24 hours post-dose. On Day 1, eligible participants will be randomized in a 1:1 ratio to either Treatment A or Treatment B. The randomization will be stratified by weight categories: >= 60 to < 70 kg, >= 70 to < 80 kg, >= 80 to < 90 kg, and >= 90 to <= 100 kg.

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Parallel-Group, Single-dose, Biocomparability Study of the Pharmacokinetics of the Abatacept (BMS-188667) Drug Product Converted From Drug Substance of a New Abatacept Drug Substance Process Relative to the Current Abatacept Drug Process in Healthy Participants
• Actual Study Start Date: Nov 9, 2018
• Actual Primary Completion Date: Apr 2, 2019
• Actual Study Completion Date: Apr 2, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A Participants will receive abatacept at a single dose of 750 mg as IV infusion on Day 1 converted from drug substance by a new process.	Drug: Abatacept; Participants will receive abatacept at a single dose 750 mg as IV infusion.
Active Comparator: Treatment B Participants will receive abatacept at a single dose 750 mg as IV infusion on Day 1 converted from drug substance by converted from drug substance by the current process.	Drug: Abatacept; Participants will receive abatacept at a single dose 750 mg as IV infusion.

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Serum Concentration (Cmax) [From drug administration to 70 days following drug administration]

   Maximum Observed Serum Concentration

2. Area Under the Curve AUC(INF) [From drug administration to 70 days following drug administration]

   Area under the serum concentration-time curve from time zero extrapolated to infinity

Secondary Outcome Measures

1. Time of Maximum Observed Serum Concentration (Tmax) [From drug administration to 70 days following drug administration]

   Time of maximum observed serum concentration

2. Area Under the Curve AUC(0-T) [From drug administration to 70 days following drug administration]

   Area under the serum concentration-time curve from zero to the last time of the last quantifiable concentration

3. Area Under the Curve AUC(0-28) [From drug administration to 70 days following drug administration]

   Area under the serum concentration-time curve from time zero to 28 days after dosing

4. Total Body Clearance (CLT) [From drug administration to 70 days following drug administration]

   Total body clearance

5. Volume of Distribution at Steady-State (Vss) [From drug administration to 70 days following drug administration]

   Volume of distribution at steady-state

6. Terminal Phase Elimination Half-life (T-HALF) [From drug administration to 70 days following drug administration]

   Terminal phase elimination half-life in serum

7. Number of Participants Experiencing Positive Immunogenicity Response to Abatacept [From Day 1 (Predose) to Day 71 (Study Discharge), assessed at day 1, day 29, day 57 and day 71]

   Positive immunogenicity response to Abatacept was defined if one of the following criteria was met: missing baseline immunogenicity measurement and a positive, post-baseline, laboratory-reported immunogenicity response; a negative laboratory-reported baseline immunogenicity response and a positive, post-baseline, laboratory-reported response; a positive, laboratory-reported, baseline immunogenicity response and a positive, post-baseline, laboratory-reported immunogenicity response with a titer value greater than the baseline titer value.

8. Number of Participants Experiencing Adverse Events [From drug administration to 56 days following drug administration]

   Number of participants experiencing different types of Adverse Events (AEs). Peri-infusional AEs: occurring during the 30 minute study drug infusion period Post-infusional AEs: occurring within 24 hours post drug infusion

9. Change From Baseline in Blood Pressure [From baseline (last result before start of study medication) to 70 days after start of study medication]

   Mean Change from Baseline in systolic and diastolic blood pressure values

10. Change From Baseline in Heart Rate [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in heart rate values

11. Change From Baseline in Respiration Rate [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in respiration rate values

12. Change From Baseline in Body Temperature [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in body temperature values

13. Change From Baseline in Electrocardiogram (ECG) Parameters [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in ECG parameters, including PR interval, QRS interval, QT interval, and QTC Fridericia

14. Number of Participants Experiencing Clinically Significant Physical Examination Abnormalities [From the pre-treatment period to 70 days after start of study medication (approximately 100 days)]

    Number of participants experiencing clinically significant physical examination abnormal findings

15. Change From Baseline in Laboratory Test Results - Hematology 1 [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in laboratory test results - Hematology parameters 1

16. Change From Baseline in Laboratory Test Results - Hematology 2 [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in laboratory test results - Hematology parameters 2

17. Change From Baseline in Laboratory Test Results - Hematology 3 [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in laboratory test results - Hematocrit

18. Change From Baseline in Laboratory Test Results - Chemistry 1 [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in laboratory test results - Chemistry parameters 1

19. Change From Baseline in Laboratory Test Results - Chemistry 2 [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in laboratory test results - Chemistry parameters 2

20. Change From Baseline in Laboratory Test Results - Chemistry 3 [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in laboratory test results - Chemistry parameters 3

21. Change From Baseline in Laboratory Test Results -Hematology and Chemistry 4 [From baseline (last result before start of study medication) to 70 days after start of study medication]

    Mean Change from Baseline in laboratory test results - hematology and chemistry parameters 4

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Body weight will be between 60 and 100 kg, inclusive.

• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 24 hours prior to the start of study treatment.

• Women must not be breastfeeding.

• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with abatacept plus 5 half-lives of abatacept (85 days) plus 30 days (duration of ovulatory cycle) for a total of 115 days post-treatment completion.

• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with abatacept plus 5 half-lives of abatacept (85 days) plus the duration of spermatogenesis (90 days) for a total of 175 days after the last dose of study treatment. In addition, male participants must be willing to refrain from sperm donation during this time.

Exclusion Criteria:

• Participants who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Participants who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.

• Participants with a history of herpes zoster.

• Donation of blood to a blood bank or in a clinical study (except a screening visit or follow-up visit) within 4 weeks of study treatment administration (within 2 weeks of study treatment administration for plasma only).

• Blood transfusion within 4 weeks of study treatment administration.

• Recent (within 6 months of study treatment administration) history of smoking or current smokers. This includes participants using electronic cigarettes or nicotine-containing products such as tobacco for chewing, nicotine patches, nicotine lozenges, or nicotine gum.

• History of allergy to abatacept or related compounds.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Qps-Mra, Llc	South Miami	Florida	United States	33143
2	PPD Development, LP	Austin	Texas	United States	78744

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 15, 2018
• Statistical Analysis Plan - Aug 28, 2019

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT03714022
• Other Study ID Numbers: IM101-682
• First Posted: Oct 22, 2018
• Last Update Posted: Jan 7, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Abatacept

Study Results

Participant Flow

Pre-assignment Detail	140 participants were randomized and treated.

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Period Title: Overall Study
STARTED	70	70
COMPLETED	66	67
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)	Total
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process	Total of all reporting groups
Overall Participants	70	70	140
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.4 (9.29)	36.6 (9.37)	36.5 (9.30)
Sex: Female, Male (Count of Participants)
Female	29 41.4%	26 37.1%	55 39.3%
Male	41 58.6%	44 62.9%	85 60.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	40 57.1%	44 62.9%	84 60%
Not Hispanic or Latino	30 42.9%	26 37.1%	56 40%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.4%	1 1.4%	2 1.4%
Asian	1 1.4%	1 1.4%	2 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	22 31.4%	29 41.4%	51 36.4%
White	45 64.3%	39 55.7%	84 60%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.4%	0 0%	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Serum Concentration (Cmax)
Description	Maximum Observed Serum Concentration
Time Frame	From drug administration to 70 days following drug administration

Outcome Measure Data

Analysis Population Description

All treated participants with available concentration-time data

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	69	70
Geometric Mean (Geometric Coefficient of Variation) [ug/mL]	237.0341 (26)	236.2882 (23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A (New Process), Cohort B (Current Process)
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence is concluded if the 90% CIs for the ratios of geometric means are contained within 0.8 to 1.25
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	0.998
	Confidence Interval	(2-Sided) 90%; 0.941 to 1.058
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cohort A vs Cohort B

2. Primary Outcome

Title	Area Under the Curve AUC(INF)
Description	Area under the serum concentration-time curve from time zero extrapolated to infinity
Time Frame	From drug administration to 70 days following drug administration

Outcome Measure Data

Analysis Population Description

All treated participants with available concentration-time data

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	69	70
Geometric Mean (Geometric Coefficient of Variation) [ug*h/mL]	35693.8 (22)	38254.6 (16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A (New Process), Cohort B (Current Process)
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence is concluded if the 90% CIs for the ratios of geometric means are contained within 0.8 to 1.25
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	0.929
	Confidence Interval	(2-Sided) 90%; 0.884 to 0.976
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cohort A vs Cohort B

3. Secondary Outcome

Title	Time of Maximum Observed Serum Concentration (Tmax)
Description	Time of maximum observed serum concentration
Time Frame	From drug administration to 70 days following drug administration

Outcome Measure Data

Analysis Population Description

All treated participants with available concentration-time data

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	69	70
Median (Full Range) [Hours]	1.000	1.000

4. Secondary Outcome

Title	Area Under the Curve AUC(0-T)
Description	Area under the serum concentration-time curve from zero to the last time of the last quantifiable concentration
Time Frame	From drug administration to 70 days following drug administration

Outcome Measure Data

Analysis Population Description

All treated participants with available concentration-time data

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	69	70
Geometric Mean (Geometric Coefficient of Variation) [ug*h/mL]	34473.2 (22)	36671.6 (16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A (New Process), Cohort B (Current Process)
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence is concluded if the 90% CIs for the ratios of geometric means are contained within 0.8 to 1.25
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	0.936
	Confidence Interval	(2-Sided) 90%; 0.891 to 0.983
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cohort A vs Cohort B

5. Secondary Outcome

Title	Area Under the Curve AUC(0-28)
Description	Area under the serum concentration-time curve from time zero to 28 days after dosing
Time Frame	From drug administration to 70 days following drug administration

Outcome Measure Data

Analysis Population Description

All treated participants with available concentration-time data

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	69	70
Geometric Mean (Geometric Coefficient of Variation) [ug*h/mL]	28597.9 (20)	29765.7 (15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A (New Process), Cohort B (Current Process)
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence is concluded if the 90% CIs for the ratios of geometric means are contained within 0.8 to 1.25
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	0.957
	Confidence Interval	(2-Sided) 90%; 0.915 to 1.001
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cohort A vs Cohort B

6. Secondary Outcome

Title	Total Body Clearance (CLT)
Description	Total body clearance
Time Frame	From drug administration to 70 days following drug administration

Outcome Measure Data

Analysis Population Description

All treated participants with available concentration-time data

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	69	70
Geometric Mean (Geometric Coefficient of Variation) [mL/h/Kg]	0.2642 (21)	0.2445 (17)

7. Secondary Outcome

Title	Volume of Distribution at Steady-State (Vss)
Description	Volume of distribution at steady-state
Time Frame	From drug administration to 70 days following drug administration

Outcome Measure Data

Analysis Population Description

All treated participants with available concentration-time data

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	69	70
Geometric Mean (Geometric Coefficient of Variation) [L/Kg]	0.10444 (21)	0.10462 (21)

8. Secondary Outcome

Title	Terminal Phase Elimination Half-life (T-HALF)
Description	Terminal phase elimination half-life in serum
Time Frame	From drug administration to 70 days following drug administration

Outcome Measure Data

Analysis Population Description

All treated participants with available concentration-time data

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	69	70
Mean (Standard Deviation) [Hours]	357.464 (78.6519)	369.425 (76.0162)

9. Secondary Outcome

Title	Number of Participants Experiencing Positive Immunogenicity Response to Abatacept
Description	Positive immunogenicity response to Abatacept was defined if one of the following criteria was met: missing baseline immunogenicity measurement and a positive, post-baseline, laboratory-reported immunogenicity response; a negative laboratory-reported baseline immunogenicity response and a positive, post-baseline, laboratory-reported response; a positive, laboratory-reported, baseline immunogenicity response and a positive, post-baseline, laboratory-reported immunogenicity response with a titer value greater than the baseline titer value.
Time Frame	From Day 1 (Predose) to Day 71 (Study Discharge), assessed at day 1, day 29, day 57 and day 71

Outcome Measure Data

Analysis Population Description

All treated participants with available concentration-time data

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	70	70
Count of Participants [Participants]	14 20%	11 15.7%

10. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events
Description	Number of participants experiencing different types of Adverse Events (AEs). Peri-infusional AEs: occurring during the 30 minute study drug infusion period Post-infusional AEs: occurring within 24 hours post drug infusion
Time Frame	From drug administration to 56 days following drug administration

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	70	70
Participants with at least 1 Adverse Event	20 28.6%	18 25.7%
Participants with at least 1 peri-infusional Adverse Event	1 1.4%	2 2.9%
Participants with at least 1 post-infusional Adverse Event	4 5.7%	3 4.3%
Participants with Adverse Event related to study drug	8 11.4%	7 10%
Death	0 0%	0 0%
Serious Adverse Events (SAEs)	0 0%	0 0%
Adverse Events leading to discontinuation	0 0%	0 0%

11. Secondary Outcome

Title	Change From Baseline in Blood Pressure
Description	Mean Change from Baseline in systolic and diastolic blood pressure values
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Systolic Blood Pressure	-0.3 (12.21)	2.0 (10.72)
Diastolic Blood Pressure	-0.8 (7.69)	-0.7 (8.52)

12. Secondary Outcome

Title	Change From Baseline in Heart Rate
Description	Mean Change from Baseline in heart rate values
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Mean (Standard Deviation) [bpm]	1.6 (9.99)	0 (9.34)

13. Secondary Outcome

Title	Change From Baseline in Respiration Rate
Description	Mean Change from Baseline in respiration rate values
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Mean (Standard Deviation) [breath/min]	1.0 (3.27)	0.5 (3.63)

14. Secondary Outcome

Title	Change From Baseline in Body Temperature
Description	Mean Change from Baseline in body temperature values
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Mean (Standard Deviation) [C]	-0.01 (0.486)	-0.06 (0.392)

15. Secondary Outcome

Title	Change From Baseline in Electrocardiogram (ECG) Parameters
Description	Mean Change from Baseline in ECG parameters, including PR interval, QRS interval, QT interval, and QTC Fridericia
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
PR Interval	1.6 (17.66)	-1.8 (10.49)
QRS Interval	1.6 (5.70)	-0.0 (5.45)
QT Interval	-1.1 (22.53)	-2.1 (17.28)
QTC Fridericia	1.4 (13.20)	0.5 (12.70)

16. Secondary Outcome

Title	Number of Participants Experiencing Clinically Significant Physical Examination Abnormalities
Description	Number of participants experiencing clinically significant physical examination abnormal findings
Time Frame	From the pre-treatment period to 70 days after start of study medication (approximately 100 days)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	70	70
Count of Participants [Participants]	0 0%	0 0%

17. Secondary Outcome

Title	Change From Baseline in Laboratory Test Results - Hematology 1
Description	Mean Change from Baseline in laboratory test results - Hematology parameters 1
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Platelet Count	3.9 (30.99)	-1.6 (31.81)
Basophils (absolute)	-0.026 (0.0741)	-0.015 (0.0292)
Eosinophils (absolute)	-0.006 (0.1006)	0.012 (0.012)
Leukocytes	0.09 (1.154)	-0.07 (1.225)
Lymphocytes (absolute)	0.073 (0.5086)	-0.028 (0.3162)
Monocytes (absolute)	-0.045 (0.1163)	-0.033 (0.1453)
Neutrophils (absolute)	0.083 (0.9523)	-0.011 (1.0654)

18. Secondary Outcome

Title	Change From Baseline in Laboratory Test Results - Hematology 2
Description	Mean Change from Baseline in laboratory test results - Hematology parameters 2
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Basophils (relative)	-0.0034 (0.00779)	-0.0023 (0.00462)
Eosinophils (relative)	-0.0008 (0.01712)	0.0024 (0.01372)
Lymphocytes (relative)	0.0107 (0.07609)	0.0019 (0.06250)
Monocytes (relative)	-0.0073 (0.01389)	-0.0041 (0.02072)
Neutrophils (relative)	0.0008 (0.08609)	0.0021 (0.07425)

19. Secondary Outcome

Title	Change From Baseline in Laboratory Test Results - Hematology 3
Description	Mean Change from Baseline in laboratory test results - Hematocrit
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Mean (Standard Deviation) [Proportion of Blood Volume]	-0.0017 (0.01845)	0.0014 (0.01767)

20. Secondary Outcome

Title	Change From Baseline in Laboratory Test Results - Chemistry 1
Description	Mean Change from Baseline in laboratory test results - Chemistry parameters 1
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Alanine Aminotransferase (ALT)	0.6 (9.01)	-1.3 (8.50)
Alkaline Phosphatase (ALP)	-3.0 (7.52)	-0.4 (8.86)
Aspartate Aminotransferase (AST)	1.1 (15.89)	-1.1 (4.11)
Lactate Dehydrogenase (LD)	1.4 (47.60)	-3.2 (18.30)

21. Secondary Outcome

Title	Change From Baseline in Laboratory Test Results - Chemistry 2
Description	Mean Change from Baseline in laboratory test results - Chemistry parameters 2
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Bilirubin, Direct	-0.01 (0.804)	-0.09 (0.759)
Bilirubin, Total	-0.25 (3.467)	-0.54 (3.297)
Creatinine	-2.2 (9.72)	-1.5 (8.58)

22. Secondary Outcome

Title	Change From Baseline in Laboratory Test Results - Chemistry 3
Description	Mean Change from Baseline in laboratory test results - Chemistry parameters 3
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Blood Urea Nitrogen	0.29 (1.264)	0.12 (1.125)
Calcium, Total	-0.027 (0.0809)	-0.012 (0.0787)
Chloride, Serum	0.4 (1.83)	-0.1 (2.01)
Magnesium, Serum	-0.011 (0.0610)	-0.015 (0.0666)
Phosphorus, Inorganic	-0.010 (0.1537)	-0.040 (0.1431)
Potassium, Serum	-0.13 (0.266)	-0.23 (0.311)
Sodium, Serum	-0.1 (2.22)	-0.2 (2.09)
Glucose, Serum	0.04 (0.516)	0.04 (0.383)
Uric Acid	0.006 (0.0425)	0.004 (0.0341)

23. Secondary Outcome

Title	Change From Baseline in Laboratory Test Results -Hematology and Chemistry 4
Description	Mean Change from Baseline in laboratory test results - hematology and chemistry parameters 4
Time Frame	From baseline (last result before start of study medication) to 70 days after start of study medication

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Cohort A (New Process)	Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
Measure Participants	67	67
Hemoglobin (g/L)	-0.6 (6.06)	0.4 (5.57)
Albumin (g/L)	-0.9 (2.53)	-0.3 (2.39)
Protein, Total (g/L)	-1.2 (4.50)	-0.4 (4.32)

Adverse Events

Time Frame	From drug administration to 70 days following drug administration
Arm/Group Title	Cohort A (New Process)		Cohort B (Current Process)
Arm/Group Description	Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process		Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process
All Cause Mortality
	Cohort A (New Process)		Cohort B (Current Process)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/70 (0%)		0/70 (0%)
Serious Adverse Events
	Cohort A (New Process)		Cohort B (Current Process)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/70 (0%)		0/70 (0%)
Other (Not Including Serious) Adverse Events
	Cohort A (New Process)		Cohort B (Current Process)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/70 (8.6%)		3/70 (4.3%)
Infections and infestations
Nasopharyngitis	6/70 (8.6%)		3/70 (4.3%)

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.