Belatacept Pharmacokinetic Trial in Renal Transplantation

NCT00578448 | Completed Phase 2 Results

• 1 other identifier: IM103-047
• Study Type: interventional
• Target: 14
• Locations: 3 countries
• Sites: 5

Brief Summary

The purpose of this study is to assess the pharmacokinetics and safety of belatacept in de novo renal transplant subjects treated with belatacept-based immunosuppressant medication

Conditions

Renal Transplantation

Outcome Measures

Primary Outcomes (7)

• Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population

  Pharmacokinetic (PK) sampling started from pre-dose (0 hour) on Day 84 and ended at 672 hour (h) on Day 112 (between Weeks 12 to 16). The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method and measured as nanograms/milliliter (ng/mL). Less than the lower limit of quantification (LLQ), 3.000 ng/mL concentration value was treated as missing.

  Day 84 to Day 112

• Maximum Observed Serum Concentration (Cmax) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept and Trough Serum Concentration Prior to Dosing (Cmin) - Pharmacokinetic Population

  Cmax, Cmin are measured in micrograms per milliliter (µg/mL). At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. Serum samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations. The Cmax, and the Cmin were recorded directly from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria, which is also referred to as adjusted R-squared. Values below lower limits of quantification (LLQ), 0.003 µg/mL, were set to 0.0015 for computation of summary statistics.

  Day 84 to Day 112

• Time of Maximum Observed Serum Concentration (Tmax) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population

  Tmax measured in hours (h). At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 (h) on Day 112 . The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations.

  Day 84 to Day 112

• Area Under the Concentration Time Curve Within a Dosing Interval (AUC) (TAU) Between Weeks 12 and 16 Following 10 mg/kg IV Belatacept - Pharmacokinetic Population

  At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). The area under the concentration-time curve in one dose interval \[AUC(TAU), where TAU = 4 weeks\] were calculated using the mixed log-linear trapezoidal algorithm in Kinetica. Actual sampling times were used for PK calculations. AUC (TAU) was measured as micrograms multiplied by time(h) per milliliter (µg\*h/mL).

  Day 82 to Day 112

• Total Body Clearance (CLT) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population

  At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations. CLT was calculated by dividing the dose by AUC(TAU) and was adjusted to body weight. CLT was measured as milliliter per time per kg body weight (mL/h/kg).

  Day 84 to Day 112

• Steady-state Volume Distribution (Vss) Following 10mg/kg IV Belatacept Between Weeks 12 and 16 - Pharmacokinetic Population

  At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations. Vss was calculated by dividing the dose by AUC and multiply the mean residence time (MRT). Vss was adjusted to body weight and measured as liter per kilogram body weight (l/kg).

  Day 84 to Day 112

• Serum Half Life (T-HALF) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population

  At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations. T-HALF was calculated as ln2/Lz, where Lz is the absolute value of the slope of the terminal log-linear phase. T-HALF is measured in hours (h).

  Day 84 to Day 112

Secondary Outcomes (4)

• Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population

  Day 1 to Day 1092

• Acute Rejection, Graft Loss, and Death up to 3 Years Post Transplantation in Planned Study and 1 Year Long Term Extension - All Treated Participants

  Day 1 up to 4 years post transplantation

• Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Tryptophan - All Treated Participants

  Baseline to Day 364

• Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Kynurenine - All Treated Participants

  Day 1 to Day 364

Study Arms (2)

A

ACTIVE COMPARATOR

10mg/kg 6 doses (Day 1, 5, week 2, 4, 8 and 12) for 12 weeks

Drug: Belatacept

B

ACTIVE COMPARATOR

5mg/kg 33 doses (every 4 weeks) for 144 weeks

Drug: Belatacept

Interventions

Belatacept DRUG

IV infusion

Also known as: BMS-224818

A; B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipient of a living or deceased donor kidney
• First or second transplant
• Men and women, including women of childbearing potential, 18 years and older

You may not qualify if:

• Panel reactive antibodies ≥ 30%
• Significant infection

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (5)

Western New England Renal & Transplant

Springfield, Massachusetts, 01107, United States

Location

Henry Ford Hospital

Detriot, Michigan, 48202, United States

Location

Local Institution

Capital Federal, Buenos Aires, 1425, Argentina

Location

Local Institution

Aguascalientes, Aguascalientes, 20219, Mexico

Location

Local Institution

Cuernavaca, Morelos, 62448, Mexico

Location

Related Links

• Investigator Inquiry form

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: March 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: September 1, 2012
• Last Updated: January 17, 2014
• Results First Posted: December 17, 2013

Record last verified: 2013-12

Locations

ME (2); US (2); AR (1)