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

• ClinicalTrials.gov Identifier: NCT00705367
• Recruitment Status: Completed
• First Posted: June 26, 2008
• Results First Posted: June 3, 2010
• Last Update Posted: July 30, 2013
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Lupus Nephritis	Drug: Placebo; Drug: Abatacept	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Study Start Date: August 2008
• Actual Primary Completion Date: January 2009
• Actual Study Completion Date: July 2011

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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.
2. 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 ]
   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).
3. Short-term Period: MeanSystolic and Diastolic Blood Pressure [ Time Frame: Day 1 predose and postdose and Day 2 ]
   Vital sign measurements are summarized without regard to position (sitting, standing, supine).
4. Short-term Period: Mean Heart Rate [ Time Frame: Day 1 predose and postdose and Day 2 ]
   Vital signs measurements are summarized without regard to position (sitting, standing, supine).
5. Short-term Period: Mean Respirations Rate [ Time Frame: Day 1 predose and postdose and Day 2 ]
   Vital sign measurements are summarized without regard to position (sitting, standing, supine).
6. Short-term Period: Mean Temperature [ Time Frame: Day 1 predose and postdose and Day 2 ]
   Vital sign measurements are summarized without regard to position (sitting, standing, supine).
7. Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities [ Time Frame: Screening and Days 1 and 2 ]
   Laboratory tests consisted of complete blood count, chemistry, and urinalysis.

Secondary Outcome Measures :

1. 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 ]
   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.
2. Minimum (Cmin) Plasma Concentration of Abatacept [ Time Frame: Days 15, 29, 85, 169, 253 and 337 ]
   Cmin is the minimum, or trough, concentration of a drug observed after its administration and just prior to the administration of a subsequent dose.
3. Maximum (Cmax) Plasma Concentration of Abatacept [ Time Frame: Postdosing Day 1 ]
   Cmax is a drug's maximum, or peak, concentration observed after its administration.
4. 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 ]
   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
5. 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 ]
   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.
6. 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 ]
   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:
7. Long-term Period: Number of Participants With Abatacept-specific Antibodies [ Time Frame: Day15 to 56 days post last dose of the long-term period ]
   Antiabatacept antibodies in human serum were assayed using a validated electrochemiluminescent immunoassay during the period of known analyte stability.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Publications:

Liu MF, Wang CR, Lin LC, Wu CR. CTLA-4 gene polymorphism in promoter and exon-1 regions in Chinese patients with systemic lupus erythematosus. Lupus. 2001;10(9):647-9.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00705367
• Other Study ID Numbers: IM101-217
• First Posted: June 26, 2008
• Results First Posted: June 3, 2010
• Last Update Posted: July 30, 2013
• Last Verified: July 2013

Additional relevant MeSH terms:

Nephritis; Lupus Nephritis; Kidney Diseases; Urologic Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Abatacept; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents