Trial Outcomes & Findings for Pharmacokinetics, Safety and Tolerability of Single-dose Belatacept in Adolescent Kidney Transplant Recipients (NCT NCT01791491)

NCT ID: NCT01791491

Last Updated: 2017-07-24

Results Overview

Cmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Cmax was measured in micrograms per milliliter.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 16 participants
• Primary outcome timeframe: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
• Results posted on: 2017-07-24

Participant Flow

16 participants were enrolled and 9 were treated. Reasons for non-treatment: 1 withdrew consent and 6 no longer met study criteria.

Participant milestones

Measure	Belatacept A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics, Safety and Tolerability of Single-dose Belatacept in Adolescent Kidney Transplant Recipients

Baseline characteristics by cohort

Measure	Belatacept n=9 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Age, Continuous	15.1 years STANDARD_DEVIATION 1.17 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Population: Pharmacokinetic (PK) analysis set: all participants who received one dose of belatacept and who had at least 1 blood sample drawn for PK determination.

Cmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Cmax was measured in micrograms per milliliter.

Outcome measures

Measure	Belatacept n=9 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Maximum Observed Serum Concentration (Cmax) of Belatacept	151 micrograms per milliliter Geometric Coefficient of Variation 20

PRIMARY outcome

Timeframe: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Population: Pharmacokinetic (PK) analysis set: all participants who received one dose of belatacept and who had at least 1 blood sample drawn for PK determination.

Tmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Tmax was measured in hours (h).

Outcome measures

Measure	Belatacept n=9 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Time of Maximum Observed Plasma Concentration (Tmax) of Belatacept	0.733 hours Interval 0.45 to 2.05

PRIMARY outcome

Timeframe: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Population: Pharmacokinetic (PK) analysis set: all participants who received one dose of belataceptand who had at least 1 blood sample drawn for PK determination.

T-HALF was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). T-HALF was measured in hours (h).

Outcome measures

Measure	Belatacept n=9 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Half-Life of Elimination (T-Half) of Belatacept	173 hours Standard Deviation 46.8

PRIMARY outcome

Timeframe: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Population: Pharmacokinetic (PK) analysis set: all participants who received one dose of belatacept and who had at least 1 blood sample drawn for PK determination.

AUC (0 - T) and AUC (0 - INF) were derived from serum concentration versus time data and measured in microgram hours per milliliter (µg*h/mL). Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL).

Outcome measures

Measure	Belatacept n=9 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC (0-T)) and Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Belatacept AUC (0-T)	15145 microgram hours per milliliter Geometric Coefficient of Variation 25
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC (0-T)) and Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Belatacept AUC(INF)	15407 microgram hours per milliliter Geometric Coefficient of Variation 25

PRIMARY outcome

Timeframe: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Population: Pharmacokinetic (PK) analysis set: all participants who received one dose of belatacept and who had at least 1 blood sample drawn for PK determination.

CLT was the volume of abatacept cleared by the system, normalized by baseline body weight. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). CLT was measured in milliliters per hours per kilogram of body weight (mL/h/kg).

Outcome measures

Measure	Belatacept n=9 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Total Body Clearance (CLT) of Belatacept	0.483 milliliters per hours per kilogram Geometric Coefficient of Variation 27

PRIMARY outcome

Timeframe: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Population: Pharmacokinetic (PK) analysis set: all participants who received one dose of belatacept and who had at least 1 blood sample drawn for PK determination.

Vss was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Vss was measured in liters per kg body weight (L/kg).

Outcome measures

Measure	Belatacept n=9 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Volume of Distribution at Steady-state (Vss) of Belatacept	0.088 Liters per kilogram Geometric Coefficient of Variation 30

SECONDARY outcome

Timeframe: Date of First Dose to 24 weeks post the last dose; approximately 26 weeks

Population: All treated participants who received at least one dose of belatacept.

Death was a fatal event leading to permanent cessations of all vital functions of the body. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Treatment related=having certain, probable, possible, or missing relationship to study drug.

Outcome measures

Measure	Belatacept n=9 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Number of Participants With Death, Serious Adverse Events (SAEs), and Treatment-related Adverse Event (AE) Death	0 participants
Number of Participants With Death, Serious Adverse Events (SAEs), and Treatment-related Adverse Event (AE) SAEs	4 participants
Number of Participants With Death, Serious Adverse Events (SAEs), and Treatment-related Adverse Event (AE) Treatment-related AEs	0 participants

SECONDARY outcome

Timeframe: Baseline/Day 1, Days 15, 29, and 57

Population: All treated participants who received at least one dose of belatacept.

Serum samples were analyzed for anti-belatacept antibodies using a validated homogenous bridging assay. The assay followed a tiered approach consistent with health authority guidance: tier 1 for screening ADA responses, tier 2 for confirming drug specificity of the ADA-positive responses, and tier 3 for titer. A neutralizing antibody assay was used to test those samples positive to the LEA29Y portion of the molecule in tier 2 and for which drug concentrations are =>1 μg/mL. Lack of immunogenicity was defined as the absence of a positive response.

Outcome measures

Measure	Belatacept n=9 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Number of Participants With Positive Belatacept-induced Immunogenicity Response	0 participants

SECONDARY outcome

Timeframe: 0.5 hours post dose on Day 1, Day 29 and Day 57

Population: Pharmacodynamic analysis set: all participants who received one dose of belatacept and who had at least 1 pharmacodynamic result (CD86 RO) reported after that dose.

Blood samples collected following the single dose belatacept infusion were assessed for CD86 receptor occupancy (CD86 RO).

Outcome measures

Measure	Belatacept n=7 Participants A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Percentage of CD86 Receptor Occupancy 0.5 Hour	94.70 percent Standard Deviation 4.035
Percentage of CD86 Receptor Occupancy Day 29	77.99 percent Standard Deviation 10.983
Percentage of CD86 Receptor Occupancy Day 57	51.45 percent Standard Deviation 43.285

Adverse Events

Belatacept

Serious events: 4 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Belatacept n=9 participants at risk A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Infections and infestations Gastroenteritis	22.2% 2/9 • Number of events 2 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
Investigations Blood creatinine increased	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
Renal and urinary disorders Acute kidney injury	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
Infections and infestations Pyelonephritis	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
Infections and infestations Pyelonephritis acute	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
Infections and infestations Urinary tract infection	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)

Other adverse events

Measure	Belatacept n=9 participants at risk A single dose of 7.5 mg/kg Belatacept was given intravenously on study Day 1 over approximately 30 minutes.
Nervous system disorders Headache	22.2% 2/9 • Number of events 3 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
Gastrointestinal disorders Abdominal pain upper	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
Gastrointestinal disorders Vomiting	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
Infections and infestations Urinary tract infection	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
General disorders Asthenia	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)
Infections and infestations Gastroenteritis	11.1% 1/9 • Number of events 1 • SAEs were reported from the date of first dose to 24 weeks post the last dose (approximately 26 weeks); AEs were reported for the on study period from the date of first dose up to 56 days post last dose (approximately 10 weeks)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER