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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03714022

Enrollment

140

Registered

2018-10-22

Start date

2018-11-09

Completion date

2019-04-02

Last updated

2021-01-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

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.

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.

Interventions

DRUGAbatacept

Participants will receive abatacept at a single dose 750 mg as IV infusion.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

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.

Design outcomes

Primary

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

Measure	Time frame	Description
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
Total Body Clearance (CLT)	From drug administration to 70 days following drug administration	Total body clearance
Volume of Distribution at Steady-State (Vss)	From drug administration to 70 days following drug administration	Volume of distribution at steady-state
Terminal Phase Elimination Half-life (T-HALF)	From drug administration to 70 days following drug administration	Terminal phase elimination half-life in serum
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: 1. missing baseline immunogenicity measurement and a positive, post-baseline, laboratory-reported immunogenicity response; 2. a negative laboratory-reported baseline immunogenicity response and a positive, post-baseline, laboratory-reported response; 3. 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.
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
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
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
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
Time of Maximum Observed Serum Concentration (Tmax)	From drug administration to 70 days following drug administration	Time of maximum observed serum concentration
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
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
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
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
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
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
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
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
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
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
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

Countries

United States

Participant flow

Pre-assignment details

140 participants were randomized and treated.

Participants by arm

Arm	Count
Cohort A (New Process) Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by a new process	70
Cohort B (Current Process) Participants received a single IV infusion (750 mg) of Abatacept drug product converted from drug substance by the current process	70
Total	140

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Consent withdrawal	0	1
Overall Study	Lost to Follow-up	3	2

Baseline characteristics

Characteristic	Cohort B (Current Process)	Total	Cohort A (New Process)
Age, Continuous	36.6 Years STANDARD_DEVIATION 9.37	36.5 Years STANDARD_DEVIATION 9.3	36.4 Years STANDARD_DEVIATION 9.29
Ethnicity (NIH/OMB) Hispanic or Latino	44 Participants	84 Participants	40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants	56 Participants	30 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) Asian	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) Black or African American	29 Participants	51 Participants	22 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) White	39 Participants	84 Participants	45 Participants
Sex: Female, Male Female	26 Participants	55 Participants	29 Participants
Sex: Female, Male Male	44 Participants	85 Participants	41 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 70	0 / 70
other Total, other adverse events	6 / 70	3 / 70
serious Total, serious adverse events	0 / 70	0 / 70

Outcome results

Primary

Area Under the Curve AUC(INF)

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

Time frame: From drug administration to 70 days following drug administration

Population: All treated participants with available concentration-time data

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort A (New Process)	Area Under the Curve AUC(INF)	35693.8 ug*h/mL	Geometric Coefficient of Variation 22
Cohort B (Current Process)	Area Under the Curve AUC(INF)	38254.6 ug*h/mL	Geometric Coefficient of Variation 16

90% CI: [0.884, 0.976]

Primary

Maximum Observed Serum Concentration (Cmax)

Maximum Observed Serum Concentration

Time frame: From drug administration to 70 days following drug administration

Population: All treated participants with available concentration-time data

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort A (New Process)	Maximum Observed Serum Concentration (Cmax)	237.0341 ug/mL	Geometric Coefficient of Variation 26
Cohort B (Current Process)	Maximum Observed Serum Concentration (Cmax)	236.2882 ug/mL	Geometric Coefficient of Variation 23

90% CI: [0.941, 1.058]

Secondary

Area Under the Curve AUC(0-28)

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

Population: All treated participants with available concentration-time data

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort A (New Process)	Area Under the Curve AUC(0-28)	28597.9 ug*h/mL	Geometric Coefficient of Variation 20
Cohort B (Current Process)	Area Under the Curve AUC(0-28)	29765.7 ug*h/mL	Geometric Coefficient of Variation 15

90% CI: [0.915, 1.001]

Secondary

Area Under the Curve AUC(0-T)

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

Population: All treated participants with available concentration-time data

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort A (New Process)	Area Under the Curve AUC(0-T)	34473.2 ug*h/mL	Geometric Coefficient of Variation 22
Cohort B (Current Process)	Area Under the Curve AUC(0-T)	36671.6 ug*h/mL	Geometric Coefficient of Variation 16

90% CI: [0.891, 0.983]

Secondary

Change From Baseline in Blood Pressure

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