Subcutaneous Pharmacokinetics of Belatacept

Pharmacokinetics, Safety and Immunogenicity of Single Doses of Belatacept Administered Subcutaneously to Healthy Subjects

Pharmacokinetics, Bioavailability, Safety and Immunogenicity of Single Doses of Belatacept Administered Subcutaneously to Healthy Subjects

Study Overview

• Status: Completed
• Conditions: Transplantation
• Intervention / Treatment: Drug: belatacept; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Ppd Development

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women ages 18 to 65 years old
• Subjects must weigh less than or equal to 100 kg

Exclusion Criteria:

• Inability to tolerate injections or IV infusions
• autoimmune disorders
• TB
• herpes
• HCV
• HBV
• HIV
• bacterial or viral infection
• history of cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Belatacept 50 mg Subcutaneous Injection; Belatacept 50 mg subcutaneous (SC) injection	Drug: belatacept; single dose, 116 days
Active Comparator: Belatacept 100 mg Subcutaneous Injection; Belatacept 100 mg SC injection	Drug: belatacept; single dose, 116 days
Active Comparator: Belatacept 125 mg Subcutaneous Injection; Belatacept 125 mg SC injection	Drug: belatacept; single dose, 116 days
Active Comparator: Belatacept 150 mg Subcutaneous Injections; 2 SC injections of 75 mg Belatacept	Drug: belatacept; single dose, 116 days
Active Comparator: Belatacept 200 mg Subcutaneous Injections; 2 SC injections of 100 mg Belatacept	Drug: belatacept; single dose, 116 days
Active Comparator: Belatacept 250 mg Subcutaneous Injections; 2 SC injections of 125 mg Belatacept	Drug: belatacept; single dose, 116 days
Active Comparator: Belatacept 125 mg Intravenous Infusion; 125 mg Belatacept intravenous (IV) injection	Drug: belatacept; single dose, 116 days
Placebo Comparator: Placebo; SC injection of placebo solution	Drug: Placebo; Subcutaneous injection of placebo solution (product ID: 224818-N000- 029)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of Belatacept	Maximum observed serum concentration (Cmax) values were derived from serum concentration versus time data and reported in micrograms per milliliter (ug/mL).	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116
Time of Maximum Observed Serum Concentration (Tmax) of Belatacept	Time of maximum observed serum concentration (Tmax) values were derived from serum concentration versus time data for all participants treated with Belatacept.	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116
Adjusted Geometric Means of Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC(0-T)) for Belatacept	Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUC(0-T)) was derived from serum concentration versus time data. Adjusted geometric means were reported in microgram hours per milliliter (ug*h/mL).	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116
Adjusted Geometric Means of Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) for Belatacept	Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was derived from serum concentration versus time data. Adjusted geometric means were reported in microgram hours per milliliter (ug*h/mL)	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116
Serum Half-life (T-HALF) of Belatacept	Serum half-life (T-HALF) was determined from serum concentration versus time data and was reported in hours.	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116
Apparent Total Body Clearance (CLT/F) of SC Belatacept	Apparent total body clearance (CLT/F) was derived from serum concentration versus time data for all participants who received subcutaneous (SC) Belatacept injections. Units reported in milliliters per hour (mL/h).	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116
Total Body Clearance (CLT) of IV Belatacept	Total body clearance (CLT) was derived from serum concentration versus time data for all participants that were treated with IV Belatacept. Units reported in milliliters per hour (mL/h)	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116
Volume of Distribution at Steady State (VSS) for IV Belatacept	Volume of distribution at steady state (VSS) was derived from serum concentration versus time data for all participants treated with IV Belatacept.	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116
Apparent Volume of Distribution at Steady State (Vss/F) for SC Belatacept	Apparent volume of distribution at steady state (Vss/F) was derived from concentration versus time data for all participants treated with subcutaneous (SC) Belatacept.	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Number of Injection Sites on Subcutaneous Belatacept Absorption	AUC(0-T) and AUC(INF) for Belatacept were derived from serum concentration versus time data to assess the effect of number of injection sites on the subcutaneous absorption of Belatacept. All treatments were dose-normalized to 50mg. Adjusted geometric means reported in microgram hours per milliliter (ug*h/mL). AUC(0-T) = Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration. AUC(INF) = Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time.	Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116
Number of Participants With Vital Sign Abnormalities	Vital signs (body temperature, respiratory rate, seated blood pressure, and heart rate) were recorded at screening. All significant findings were evaluated by the investigator, and all abnormalities were listed.	1 day pre-dose, Days 1, 2, 5, 14, 28, 42, 86 and 116
Number of Participants With Injection Site Reactions	Participants were assessed for erythema, heat, pain, pruritis and swelling at the injection sites and were characterized by the investigator as mild, moderate or severe reactions.	0.5, 2, 6 and 24 hours post-dose, Days 3, 4, 5, 6, 7, 8, 14, 21 and 116
Number of Participants With Physical Examination Abnormalities	All clinically significant deviations from normal physical examinations were reported.	Days 1, 2, 5, 14, 28, 42, 86, 116
Number of Participants With Electrocardiogram (ECG) Abnormalities	Participants underwent a 12-lead ECG assessment at Screening (Day 1) and Study Discharge (Day 116). All investigator-assessed ECG abnormalities were reported.	Days 1 and 116
Number of Participants With Marked Hematology Laboratory Abnormalities	LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose. Lab values that met the following criteria were marked as abnormalities: Hemoglobin (grams per deciliter:g/dL): <0.85*Pre-Rx. Hematocrit (%): <0.85*Pre-Rx. Platelet Count (*10^9 cells per liter:c/L): <0.85*LLN or >1.5*ULN (if Pre-Rx<LLN, use <0.85*Pre-Rx). Leukocytes (*10^3 cells per microliter: c/uL): <0.9*LLN, >1.2*ULN (if Pre-Rx<LLN, use <0.85*Pre-Rx or >ULN, if Pre-Rx>ULN, use >1.15*Pre-Rx or <LLN) Neutrophils+Bands (*10^3 c/uL): <=1.500. Lymphocytes (*10^3 c/uL): <0.750 or >7.500. Monocytes (*10^3 c/uL): >2.000. Basophils (*10^3 c/uL): >0.400. Eosinophils (*10^3 c/uL): >0.750.	Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116
Number of Participants With Marked Serum Chemistry Abnormalities	LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose. Lab values that met the following criteria were marked as abnormalities: Alkaline Phosphatase (units per liter: U/L), Aspartate Aminotransferase (U/L), Alanine Aminotransferase (U/L): >1.25*ULN (if Pre-Rx>ULN, use >1.25*Pre-Rx). Bilirubin (milligrams per deciliter: mg/dL): >1.1*ULN (if Pre-Rx>ULN, use >1.25*Pre-Rx). Blood Urea Nitrogen (mg/dL): >1.1*ULN (if Pre-Rx>ULN, use >1.2*Pre-Rx). Creatinine (mg/dL): >1.33*Pre-Rx. Sodium (milliequivalents per Liter: mEq/L): <0.95*LLN, >1.05*ULN (if Pre-Rx<LLN: <0.95*Pre-Rx, >ULN. If Pre-Rx>ULN: >1.05*Pre-Rx, <LLN). Potassium(mEq/L), Chloride (mEq/L), Calcium(mg/dL): <0.9*LLN, >1.1*ULN (if Pre-Rx<LLN: <0.9*Pre-Rx, >ULN. If Pre-Rx>ULN: >1.1*Pre-Rx, <LLN). Phosphorus (mg/dL): <0.85*LLN, >1.25*ULN (if Pre-Rx<LLN, <0.85*Pre-Rx, >ULN. if Pre-Rx>ULN: >1.25*Pre-Rx, <LLN).	Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116
Number of Participants With Marked Laboratory Abnormalities	LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose. Lab values that met the following criteria were marked as abnormalities: Glucose (mg/dL): <0.8*LLN, >1.5*ULN (if Pre-Rx<LLN: <0.8*Pre-Rx, >ULN. If Pre-Rx>ULN: >2.0*Pre-Rx, <LLN). Protein (grams per deciliter: g/dL): <0.9*LLN, >1.1*ULN (if Pre-Rx<LLN: <0.9*Pre-Rx, >ULN. If Pre-Rx>ULN: >1.1*Pre-Rx, <LLN). Albumin (g/dL): <0.9*LLN (if Pre-Rx<LLN: <0.9*Pre-Rx). Uric Acid (mg.dL): >1.2*ULN (if Pre-Rx>ULN: >1.25*Pre-Rx). Lactate Dehydrogenase (U/L): >1.25*ULN (if Pre-Rx>ULN: >1.5*Pre-Rx)	Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116
Number of Participants With Positive Immunogenicity to Belatacept	The number of participants with positive immunogenicity to Belatacept was reported for each arm. Positive immunogenicity was defined as the presence of a positive antibody response generated against Belatacept.	Days 1, 14, 28, 42, 56, 86, 116

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: November 30, 2007
• First Submitted That Met QC Criteria: December 6, 2007
• First Posted (Estimate): December 7, 2007

Study Record Updates

• Last Update Posted (Estimate): September 22, 2016
• Last Update Submitted That Met QC Criteria: August 16, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: IM103-046