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Pharmacokinetics, Bioavailability, Safety and Immunogenicity of Single Doses of Belatacept Administered Subcutaneously to Healthy Subjects
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Belatacept 50 mg Subcutaneous Injection | Active Comparator | Belatacept 50 mg subcutaneous (SC) injection |
|
| Belatacept 100 mg Subcutaneous Injection | Active Comparator | Belatacept 100 mg SC injection |
|
| Belatacept 125 mg Subcutaneous Injection | Active Comparator | Belatacept 125 mg SC injection |
|
| Belatacept 150 mg Subcutaneous Injections | Active Comparator | 2 SC injections of 75 mg Belatacept |
|
| Belatacept 200 mg Subcutaneous Injections | Active Comparator | 2 SC injections of 100 mg Belatacept |
|
| Belatacept 250 mg Subcutaneous Injections | Active Comparator | 2 SC injections of 125 mg Belatacept |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| belatacept | Drug | single dose, 116 days |
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ppd Development | Austin | Texas | 78744 | United States |
153 participants were enrolled, with 106 discontinuing prior to study drug administration because they no longer met study criteria or they withdrew consent. 47 participants met all eligibility criteria and received study medication. 1 subject, who received an incomplete dose due to an injection syringe leak, was replaced.
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| ID | Title | Description |
|---|---|---|
| FG000 | Belatacept 50 mg Subcutaneous Injection | Belatacept 50 mg subcutaneous (SC) injection into anterior thigh, 0.4 mL injection volume |
| FG001 | Belatacept 100 mg Subcutaneous Injection | Belatacept 100 mg SC injection into anterior thigh, 0.8 mL injection volume |
| FG002 | Belatacept 125 mg Subcutaneous Injection | Belatacept 125 mg SC injection into anterior thigh, 1.0 mL injection volume |
| FG003 | Belatacept 150 mg Subcutaneous Injections | Participants received 2 SC injections of 75 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. |
| FG004 | Belatacept 200 mg Subcutaneous Injections | Participants received 2 SC injections of 100 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. |
| FG005 | Belatacept 250 mg Subcutaneous Injections | Participants received 2 SC injections of 125 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. |
| FG006 | Belatacept 125 mg Intravenous Infusion | 125 mg Belatacept intravenous (IV) injection |
| FG007 | Placebo | Subcutaneous injection of placebo solution (product ID: 224818-N000- 029) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Belatacept 50 mg Subcutaneous Injection | Belatacept 50 mg subcutaneous (SC) injection into anterior thigh, 0.4 mL injection volume |
| BG001 | Belatacept 100 mg Subcutaneous Injection |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | All participants treated with Belatacept | Posted | Geometric Mean | Geometric Coefficient of Variation | 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 |
|
From Day 1 until 30 days post discontinuation of dosing, up to August 2008 (approximately 8 months)
Study initiated: December 2007
Study completed: August 2008
Participants underwent regularly scheduled investigator assessments and clinical laboratory evaluations as described in the study protocol.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Belatacept 50mg SC | Belatacept 50 mg subcutaneous (SC) injection into anterior thigh, 0.4 mL injection volume |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
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| ID | Term |
|---|---|
| D000069594 | Abatacept |
| ID | Term |
|---|---|
| D018796 | Immunoconjugates |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D012712 | Serum Globulins |
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|
| Belatacept 125 mg Intravenous Infusion | Active Comparator | 125 mg Belatacept intravenous (IV) injection |
|
| Placebo | Placebo Comparator | SC injection of placebo solution |
|
| Placebo | Drug | Subcutaneous injection of placebo solution (product ID: 224818-N000- 029) |
|
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 |
| 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, \ | 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 |
| injection syringe leaked during dosing |
|
| Withdrawal by Subject |
|
Belatacept 100 mg SC injection into anterior thigh, 0.8 mL injection volume
| BG002 | Belatacept 125 mg Subcutaneous Injection | Belatacept 125 mg SC injection into anterior thigh, 1.0 mL injection volume |
| BG003 | Belatacept 150 mg Subcutaneous Injections | Participants received 2 SC injections of 75 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. |
| BG004 | Belatacept 200 mg Subcutaneous Injections | Participants received 2 SC injections of 100 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. |
| BG005 | Belatacept 250 mg Subcutaneous Injections | Participants received 2 SC injections of 125 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. |
| BG006 | Belatacept 125 mg Intravenous Infusion | 125 mg Belatacept intravenous (IV) injection |
| BG007 | Placebo | Subcutaneous injection of placebo solution (product ID: 224818-N000- 029) |
| BG008 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Belatacept 100 mg SC injection into anterior thigh, 0.8 mL injection volume
| OG002 | Belatacept 125 mg Subcutaneous Injection | Belatacept 125 mg SC injection into anterior thigh, 1.0 mL injection volume |
| OG003 | Belatacept 150 mg Subcutaneous Injections | Participants received 2 SC injections of 75 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. |
| OG004 | Belatacept 200 mg Subcutaneous Injections | Participants received 2 SC injections of 100 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. |
| OG005 | Belatacept 250 mg Subcutaneous Injections | Participants received 2 SC injections of 125 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. |
| OG006 | Belatacept 125 mg Intravenous Infusion | 125 mg Belatacept intravenous (IV) injection |
|
|
| Primary | 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. | All participants treated with Belatacept | Posted | Median | Full Range | 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 |
|
|
|
| Primary | 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). | All participants treated with Belatacept | Posted | Geometric Mean | 90% Confidence Interval | 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 |
|
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|
| Primary | 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) | All participants treated with Belatacept | Posted | Geometric Mean | 90% Confidence Interval | 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 |
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| Primary | 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. | All participants treated with Belatacept | Posted | Mean | Standard Deviation | 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 |
|
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|
| Primary | 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). | All participants treated with SC Belatacept | Posted | Geometric Mean | Geometric Coefficient of Variation | 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 |
|
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| Primary | 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) | All participants treated with IV Belatacept | Posted | Geometric Mean | Geometric Coefficient of Variation | 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 |
|
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|
| Primary | 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. | All participants treated with IV Belatacept | Posted | Mean | Standard Deviation | Liters | 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 |
|
|
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| Primary | 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. | All participants treated with SC Belatacept | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | 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 |
|
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| Secondary | 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. | All participants treated with Belatacept | Posted | Geometric Mean | 90% Confidence Interval | 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 |
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| Secondary | 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. | All treated participants | Posted | Number | participants | 1 day pre-dose, Days 1, 2, 5, 14, 28, 42, 86 and 116 |
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| Secondary | 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. | All treated participants | Posted | Number | participants | 0.5, 2, 6 and 24 hours post-dose, Days 3, 4, 5, 6, 7, 8, 14, 21 and 116 |
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| Secondary | Number of Participants With Physical Examination Abnormalities | All clinically significant deviations from normal physical examinations were reported. | All treated participants | Posted | Number | participants | Days 1, 2, 5, 14, 28, 42, 86, 116 |
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| Secondary | 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. | All treated participants | Posted | Number | participants | Days 1 and 116 |
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| Secondary | 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. | All treated participants | Posted | Number | participants | Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116 |
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| Secondary | 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, \ | All treated participants | Posted | Number | participants | Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116 |
|
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| Secondary | 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) | All treated participants | Posted | Number | participants | Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116 |
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|
|
| Secondary | 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. | All participants treated with Belatacept | Posted | Number | participants | Days 1, 14, 28, 42, 56, 86, 116 |
|
|
|
| 0 |
| 5 |
| 2 |
| 5 |
| EG001 | Belatacept 100mg SC | Belatacept 100 mg SC injection into anterior thigh, 0.8 mL injection volume | 0 | 5 | 3 | 5 |
| EG002 | Belatacept 125mg SC | Belatacept 125 mg SC injection into anterior thigh, 1.0 mL injection volume | 0 | 5 | 3 | 5 |
| EG003 | Belatacept 150mg SC | Participants received 2 SC injections of 75 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. | 0 | 6 | 4 | 6 |
| EG004 | Belatacept 200mg SC | Participants received 2 SC injections of 100 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. | 0 | 5 | 2 | 5 |
| EG005 | Belatacept 250mg SC | Participants received 2 SC injections of 125 mg Belatacept each, in the anterior thighs. One injection was given in each thigh, with the second injection immediately following the first injection. | 0 | 5 | 2 | 5 |
| EG006 | Belatacept 125mg IV | 125 mg Belatacept intravenous (IV) injection | 0 | 10 | 7 | 10 |
| EG007 | PLACEBO | Subcutaneous injection of placebo solution (product ID: 224818-N000- 029) | 0 | 6 | 1 | 6 |
| EG008 | All Belatacept | All participants treated with IV or SC Belatacept of any dose | 0 | 41 | 23 | 41 |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Arthropod sting | Injury, poisoning and procedural complications | MedDRA 11.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Injection site inflammation | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Joint sprain | Injury, poisoning and procedural complications | MedDRA 11.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Mass | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Gynaecomastia | Reproductive system and breast disorders | MedDRA 11.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Muscle contractions involuntary | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA 11.0 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
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.
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D005916 | Globulins |
| Ratio of Geometric Means |
| 0.61 |
| 2-Sided |
| 90 |
| 0.48 |
| 0.77 |
Ratio of Geometric Means: 100mg SC over 125mg IV |
| No |
| Superiority or Other |
| Ratio of Geometric Means | 0.78 | 2-Sided | 90 | 0.62 | 0.99 | Ratio of Geometric Means: 125mg SC over 125mg IV | No | Superiority or Other |
| Ratio of Geometric Means | 0.89 | 2-Sided | 90 | 0.71 | 1.13 | Ratio of Geometric Means: 150mg SC over 125mg IV | No | Superiority or Other |
| Ratio of Geometric Means | 0.88 | 2-Sided | 90 | 0.69 | 1.11 | Ratio of Geometric Means: 200mg SC over 125mg IV | No | Superiority or Other |
| Ratio of Geometric Means | 0.73 | 2-Sided | 90 | 0.57 | 0.92 | Ratio of Geometric Means: 250mg SC over 125mg IV | No | Superiority or Other |
| Ratio of Geometric Means |
| 0.61 |
| 2-Sided |
| 90 |
| 0.48 |
| 0.77 |
Ratio of Geometric Means: 100mg SC over 125mg IV |
| No |
| Superiority or Other |
| Ratio of Geometric Means | 0.79 | 2-Sided | 90 | 0.62 | 1.00 | Ratio of Geometric Means: 125mg SC over 125mg IV | No | Superiority or Other |
| Ratio of Geometric Means | 0.90 | 2-Sided | 90 | 0.71 | 1.14 | Ratio of Geometric Means: 150mg SC over 125mg IV | No | Superiority or Other |
| Ratio of Geometric Means | 0.88 | 2-Sided | 90 | 0.69 | 1.12 | Ratio of Geometric Means: 200mg SC over 125mg IV | No | Superiority or Other |
| Ratio of Geometric Means | 0.73 | 2-Sided | 90 | 0.57 | 0.92 | Ratio of Geometric Means: 250mg SC over 125mg IV | No | Superiority or Other |
| Ratio of Geometric Means |
| 0.90 |
| 2-Sided |
| 90 |
| 0.75 |
| 1.07 |
AUC(INF) Ratio of Geometric Means: 1 injection site over 2 injection sites |
| No |
| Superiority or Other |
| moderate reaction |
|
| severe reaction |
|
| Study Discharge (Day 116) |
|
| Hematocrit |
|
| Platelet Count |
|
| Leukocytes |
|
| Neutrophils + Bands (absolute) |
|
| Lymphocytes (absolute) |
|
| Monocytes (absolute) |
|
| Basophils (absolute) |
|
| Eosinophils (absolute) |
|
| Aspartate Aminotransferase |
|
| Alanine Aminotransferase |
|
| Bilirubin |
|
| Blood Urea Nitrogen |
|
| Creatinine |
|
| Sodium, Serum |
|
| Potassium, Serum |
|
| Chloride, Serum |
|
| Calcium, Total |
|
| Phosphorus, Inorganic |
|
| Protein, Total |
|
| Albumin |
|
| Uric Acid |
|
| Lactate Dehydrogenase |
|