Phase I Study in China - Tolerability of a Single Dose of Abatacept 30 mg/kg

Bristol-Myers Squibb13 enrolled

Overview

The purpose of this study is to determine whether abatacept at a dose 30 mg/kg via intravenous infusion is safe and well tolerated in the treatment of lupus nephritis in mainland Chinese subjects with systemic lupus erythematosus (SLE)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Lupus Nephritis

Interventions

PlaceboDRUG

Infusion, Intravenous, single dose, Day 1

AbataceptDRUG

Infusion, Intravenous, 30mg/kg, single dose, Day 1

AbataceptDRUG

Infusion, intravenous, 10 mg/kg, administered on Days 15 and 29 followed by doses every 4 weeks until the end of the study

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Men and women, at least 18 years of age, with a diagnosis of systemic lupus erythematosus (SLE) and with lupus nephritis currently stable for the last 3 months without change in treatment for lupus nephritis * Stable renal disease * No flaring of other organ systems in a minimum of the last 3 months Exclusion Criteria: * Unstable lupus nephritis and serum creatinine \>3 mg/dL * Progressive renal failure, end stage renal disease, or renal transplant requiring continuous dialysis * Severe unstable, refractory, or progressive SLE * History of cancer * Participants at risk for tuberculosis * Autoimmune disease other than SLE as main diagnosis * Human immunodeficiency virus or herpes zoster infection * Hepatitis-B surface antigen-positive or hepatitis C antibody-positive participants

Locations (1)

Local Institution

Shanghai, Shanghai Municipality, China

Outcomes

Primary Outcomes

Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.

Time frame: From Day 1 of double-blind period to 1st dose of long-term period

Short-term Period: Number of Adverse Events (AEs) Related to Study Drug

Time frame: From Day 1 of double-blind period to 1st dose of long-term period

Short-term Period: MeanSystolic and Diastolic Blood Pressure

Vital sign measurements are summarized without regard to position (sitting, standing, supine).

Time frame: Day 1 predose and postdose and Day 2

Short-term Period: Mean Heart Rate

Vital signs measurements are summarized without regard to position (sitting, standing, supine).

Time frame: Day 1 predose and postdose and Day 2

Short-term Period: Mean Respirations Rate

Vital sign measurements are summarized without regard to position (sitting, standing, supine).

Time frame: Day 1 predose and postdose and Day 2

Data from ClinicalTrials.gov

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Secondary Outcomes

Long-term Period: Number of Participants With Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs

AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.

Time frame: Days 15 to 56 days post last dose of the long-term period

Minimum (Cmin) Plasma Concentration of Abatacept

Cmin is the minimum, or trough, concentration of a drug observed after its administration and just prior to the administration of a subsequent dose.

Time frame: Days 15, 29, 85, 169, 253 and 337

Maximum (Cmax) Plasma Concentration of Abatacept

Cmax is a drug's maximum, or peak, concentration observed after its administration.

Time frame: Postdosing Day 1

Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests

preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. hemoglobin (g/dL): \>3g/dL drop from preRX; hematocrit (%): \<0.75\*preRX; erythrocytes (\*10\^6 c/uL): \<0.75\*preRX; platelet count (\*10\^9 c/L): \<0.67\*LLN or \>1.5\*ULN, or \<100,000/mm\^3 or if preRX\<LLN, use \<0.5\*preRX and \<100,000/mm\^3; leukocytes (\*10\^3 c/uL): \<0.75\*LLN, \>1.25\*ULN, \<0.8\*preRX if preRX \<LLN or \>1.2\*preRX if preRX \>ULN; \>ULN if preRX \<LLN, \<LLN if \>ULN preRX; neutrophils+bands (\*10\^3 c/uL): if value \<1.00\*10\^3 c/uL; lymphocytes (\*10\^3 c/uL): if value \<0.750\*10\^3 c/uL or if value \>7.50\*10\^3 c/uL; monocytes (\*10\^3 c/uL): if value \>2000/mm\^3; basophils (\*10\^3 c/uL): if value \>400/mm\^3; eosinophils (\*10\^3 c/uL): if value\> 0.750\*10\^3 c/uL

Time frame: Days 15 to 56 days post last dose of the long-term period

Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued)

preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. Glucose (mg/dL): \<65 or \>220. Glucose, fasting(mg/dL): \<0.8\*LLN or \>1.5\* ULN; if preRX\<LLN, use \<0.8\*preRX or \>ULN; if preRX\>ULN, use \>2.0\*preRX or \<LLN. Protein, total (g/dL): \<0.9\*LLN or \>1.1\*ULN; if preRX\<LLN, use 0.9\*preRX or \>ULN if preRX \>ULN, use 1.1\*preRX or \<LLN. Albumin (g/dL): \<0.9\*LLN, or if preRX\<LLN use \<0.75\*preRX. Uric acid (mg/dL): \>1.5\*ULN; if preRX\>ULN use \>2\*preRX. Protein, urine: if missing preRX, use\>=2; if \>=4; if preRX=0 or 0.5, use \>=2; if preRX=1, use \>=3, or if preRX=2 or 3, use \>= 4. Glucose, urine: if preRX missing, use \>=2; if \>=4, or if preRX=0 or 0.5 use \>=2,or if preRX=1, use \>=3, or if preRX=2 or 3 use \>=4. Blood, urine: if preRX missing, use\>= 2, or if \>=4, or if preRX=0 or 0.5, use \>=2, or if preRX=1, use \>=3; if preRX=2 or 3 use \>=4. WBC, urine (hpf): if missing preRX, use\>= 2, or if \>= 4, or if preRX =0 or 0.5 use \>=2, or if preRX=1 use \>=3, or if preRX=2 or 3 use \>=4.

Time frame: Days 15 to 56 days post last dose of the long-term period

Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued)

ULN=upper limit of normal; preRX=pretreatment: ALP (U/L): \>2\*ULN, or if preRX\>ULN, use \>3\*preRX; AST (U/L): \>3\*ULN, or if preRX\>ULN, use \>4\*preRX; ALT (U/L): \>3X\*ULN, or if preRX\>ULN, use \>4\*preRX; GGT (/L): \>\*ULN, or if preRX\>ULN, use \>3\*preRX; bilirubin (mg/dL): \>2\*ULN, or if preRX\>ULN, use \>4\*preRX; BUN (mg/dL):\>2\*preRX; sodium: \<.95\*LLN, \>1.05\*ULN, \<.95\* preRX if \<LLN preRX, \>1.05\*preRX if \>ULN preRX; \>ULN if \<LLN preRX, \<LLN if \>ULN preRX; potassium: chloride: calcium: phosphorous:

Time frame: Days 15 to 56 days post last dose of the long-term period

Long-term Period: Number of Participants With Abatacept-specific Antibodies

Antiabatacept antibodies in human serum were assayed using a validated electrochemiluminescent immunoassay during the period of known analyte stability.

Time frame: Day15 to 56 days post last dose of the long-term period