Pharmacokinetics, Safety and Tolerability of Single-dose Belatacept in Adolescent Kidney Transplant Recipients

NCT01791491 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IM103-1442011-005257-31
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to evaluate how well adolescent kidney transplant patients tolerate a single dose of belatacept they receive at least 6 months after transplant surgery, and how their body handles the drug.

Conditions

Kidney Transplant

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Serum Concentration (Cmax) of Belatacept

  Cmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Cmax was measured in micrograms per milliliter.

  Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

• Time of Maximum Observed Plasma Concentration (Tmax) of Belatacept

  Tmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Tmax was measured in hours (h).

  Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

• Half-Life of Elimination (T-Half) of Belatacept

  T-HALF was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). T-HALF was measured in hours (h).

  Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

• Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC (0-T)) and Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Belatacept

  AUC (0 - T) and AUC (0 - INF) were derived from serum concentration versus time data and measured in microgram hours per milliliter (µg\*h/mL). Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL).

  Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

• Total Body Clearance (CLT) of Belatacept

  CLT was the volume of abatacept cleared by the system, normalized by baseline body weight. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). CLT was measured in milliliters per hours per kilogram of body weight (mL/h/kg).

  Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

• Volume of Distribution at Steady-state (Vss) of Belatacept

  Vss was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Vss was measured in liters per kg body weight (L/kg).

  Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Secondary Outcomes (3)

• Number of Participants With Death, Serious Adverse Events (SAEs), and Treatment-related Adverse Event (AE)

  Date of First Dose to 24 weeks post the last dose; approximately 26 weeks

• Number of Participants With Positive Belatacept-induced Immunogenicity Response

  Baseline/Day 1, Days 15, 29, and 57

• Percentage of CD86 Receptor Occupancy

  0.5 hours post dose on Day 1, Day 29 and Day 57

Study Arms (1)

Belatacept

EXPERIMENTAL

Drug: Belatacept

Interventions

Belatacept DRUG

Single intravenous infusion of belatacept, 7.5 mg/kg

Also known as: BMS-224818

Belatacept

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male and Female subjects,12-17 years old
• Receiving CNI-based maintenance immunosuppression since the time of renal transplantation in accordance with local standard of care
• Stable renal function, in the opinion of the investigator, with a cGFR\>45 mL/min/1.73m2 at the time of enrollment (per updated Schwartz Formula)
• Adolescent Recipients of a renal allograft from a living donor or a deceased donor at least 6 months prior to enrollment
• Subject must be receiving a calcineurin inhibitor (CNI)-based \[cyclosporine (CsA) \[any formulation\] or Tacrolimus (TAC)\] immunosuppressive regimen
• Subject must be receiving adjunctive background maintenance immunosuppression with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS)/mycophenolic acid (MPA)
• Subjects may be receiving maintenance corticosteroids in accordance with the local standard of care
• Negative Interferon Gamma Release Assay (IGRA) such as QuantiFERON-TB Gold test or T-Spot-TB
• FOCBP must have negative serum or urine pregnancy test within 24 hrs prior to start of study medication
• Subject must have stable estimated glomerular filtration rate (GFR) ≥45 mL/min/1.73m2 (updated Schwartz formula)

You may not qualify if:

• Epstein-Barr virus (EBV) serostatus negative or unknown at time of transplant and screening
• History of any treated or biopsy proven acute rejection (BPAR) within 3 months prior to enrollment
• Subjects who have experienced more than 1 episode of acute rejection (AR) of the current allograft or any antibody-mediated AR
• Subjects with any active infection \[including, but not limited to, positive cytomegalovirus (CMV) or BK viral (BKV) loads, BKV associated nephropathy (BKVAN), CMV retinitis, CMV colitis, etc.\]
• Urine albumin:creatinine ratio \> 56.5 mg/mmol (\> 0.5 mg albumin / mg creatinine) on a random voided urine specimen

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (8)

University Of Alabama At Birmingham

Birmingham, Alabama, 35233, United States

Location

Childrens Hospital Of La

Los Angeles, California, 90027, United States

Location

University Of California Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Childrens National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Boston Childrens Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Interventions

Abatacept

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2013
• First Posted: February 15, 2013
• Study Start: May 9, 2013
• Primary Completion: December 6, 2016
• Study Completion: December 6, 2016
• Last Updated: July 24, 2017
• Results First Posted: June 26, 2017

Record last verified: 2017-06

Locations

US (8)