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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00705367
First received: June 24, 2008
Last updated: July 23, 2013
Last verified: July 2013
  Purpose

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)


Condition Intervention Phase
Lupus Nephritis
Drug: Placebo
Drug: Abatacept
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Single Center, Randomized, Placebo-Controlled, Double Blind, Parallel Group Study to Evaluate the Tolerability of a Single Dose of Abatacept 30 mg/kg Via Intravenous Infusion in Chinese SLE Subjects With Lupus Nephritis

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs [ Time Frame: From Day 1 of double-blind period to 1st dose of long-term period ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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. Intensity = mild (grade 1), moderate (grade 2), severe (grade 3), life-threatening/disabling (grade 4).

  • Short-term Period: MeanSystolic and Diastolic Blood Pressure [ Time Frame: Day 1 predose and postdose and Day 2 ] [ Designated as safety issue: Yes ]
    Vital sign measurements are summarized without regard to position (sitting, standing, supine).

  • Short-term Period: Mean Heart Rate [ Time Frame: Day 1 predose and postdose and Day 2 ] [ Designated as safety issue: Yes ]
    Vital signs measurements are summarized without regard to position (sitting, standing, supine).

  • Short-term Period: Mean Respirations Rate [ Time Frame: Day 1 predose and postdose and Day 2 ] [ Designated as safety issue: Yes ]
    Vital sign measurements are summarized without regard to position (sitting, standing, supine).

  • Short-term Period: Mean Temperature [ Time Frame: Day 1 predose and postdose and Day 2 ] [ Designated as safety issue: Yes ]
    Vital sign measurements are summarized without regard to position (sitting, standing, supine).

  • Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities [ Time Frame: Screening and Days 1 and 2 ] [ Designated as safety issue: Yes ]
    Laboratory tests consisted of complete blood count, chemistry, and urinalysis.


Secondary Outcome Measures:
  • Long-term Period: Number of Participants With Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs [ Time Frame: Days 15 to 56 days post last dose of the long-term period ] [ Designated as safety issue: Yes ]
    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.

  • Minimum (Cmin) Plasma Concentration of Abatacept [ Time Frame: Days 15, 29, 85, 169, 253 and 337 ] [ Designated as safety issue: No ]
    Cmin is the minimum, or trough, concentration of a drug observed after its administration and just prior to the administration of a subsequent dose.

  • Maximum (Cmax) Plasma Concentration of Abatacept [ Time Frame: Postdosing Day 1 ] [ Designated as safety issue: No ]
    Cmax is a drug's maximum, or peak, concentration observed after its administration.

  • Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests [ Time Frame: Days 15 to 56 days post last dose of the long-term period ] [ Designated as safety issue: Yes ]
    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

  • Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) [ Time Frame: Days 15 to 56 days post last dose of the long-term period ] [ Designated as safety issue: Yes ]
    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.

  • Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) [ Time Frame: Days 15 to 56 days post last dose of the long-term period ] [ Designated as safety issue: Yes ]
    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:

  • Long-term Period: Number of Participants With Abatacept-specific Antibodies [ Time Frame: Day15 to 56 days post last dose of the long-term period ] [ Designated as safety issue: Yes ]
    Antiabatacept antibodies in human serum were assayed using a validated electrochemiluminescent immunoassay during the period of known analyte stability.


Enrollment: 13
Study Start Date: August 2008
Study Completion Date: July 2011
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Infusion, Intravenous, single dose, Day 1
Active Comparator: Abatacept, 30 mg/kg Drug: Abatacept
Infusion, Intravenous, 30mg/kg, single dose, Day 1
Other Names:
  • Orencia
  • BMS-188667
Abatacept, 10 mg/kg
Open-label long-term extension phase
Drug: Abatacept
Infusion, intravenous, 10 mg/kg, administered on Days 15 and 29 followed by doses every 4 weeks until the end of the study
Other Names:
  • Orencia
  • BMS-188667

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00705367

Locations
China, Shanghai
Local Institution
Shanghai, Shanghai, China, 200001
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00705367     History of Changes
Other Study ID Numbers: IM101-217
Study First Received: June 24, 2008
Results First Received: May 4, 2010
Last Updated: July 23, 2013
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Autoimmune Diseases
Connective Tissue Diseases
Glomerulonephritis
Immune System Diseases
Kidney Diseases
Lupus Erythematosus, Systemic
Urologic Diseases
Abatacept
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014