A Study to Evaluate the Pharmacokinetics of Abatacept Converted From Drug Substance by Two Different Processes

A Randomized, Open-Label, Parallel-Group, Single-dose, Biocomparability Study of the Pharmacokinetics of the Abatacept (BMS-188667) Drug Product Converted From Drug Substance of a New Abatacept Drug Substance Process Relative to the Current Abatacept Drug Process in Healthy Participants

The main objective of this study is to compare the pharmacokinetics (PK) of the abatacept drug product converted from drug substance by a new drug substance process (Treatment A) relative to the current drug substance process (Treatment B) following a single dose (750 mg) intravenous (IV) infusion in healthy participants.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Abatacept

Detailed Description

Participants will be admitted to the clinical facility the day prior to dosing (Day -1) and will be confined until at least 24 hours post-dose. On Day 1, eligible participants will be randomized in a 1:1 ratio to either Treatment A or Treatment B. The randomization will be stratified by weight categories: >= 60 to < 70 kg, >= 70 to < 80 kg, >= 80 to < 90 kg, and >= 90 to <= 100 kg.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body weight will be between 60 and 100 kg, inclusive.
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 24 hours prior to the start of study treatment.
• Women must not be breastfeeding.
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with abatacept plus 5 half-lives of abatacept (85 days) plus 30 days (duration of ovulatory cycle) for a total of 115 days post-treatment completion.
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with abatacept plus 5 half-lives of abatacept (85 days) plus the duration of spermatogenesis (90 days) for a total of 175 days after the last dose of study treatment. In addition, male participants must be willing to refrain from sperm donation during this time.

Exclusion Criteria:

• Participants who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Participants who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.
• Participants with a history of herpes zoster.
• Donation of blood to a blood bank or in a clinical study (except a screening visit or follow-up visit) within 4 weeks of study treatment administration (within 2 weeks of study treatment administration for plasma only).
• Blood transfusion within 4 weeks of study treatment administration.
• Recent (within 6 months of study treatment administration) history of smoking or current smokers. This includes participants using electronic cigarettes or nicotine-containing products such as tobacco for chewing, nicotine patches, nicotine lozenges, or nicotine gum.
• History of allergy to abatacept or related compounds.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment A; Participants will receive abatacept at a single dose of 750 mg as IV infusion on Day 1 converted from drug substance by a new process.	Drug: Abatacept; Participants will receive abatacept at a single dose 750 mg as IV infusion.
ACTIVE_COMPARATOR: Treatment B; Participants will receive abatacept at a single dose 750 mg as IV infusion on Day 1 converted from drug substance by converted from drug substance by the current process.	Drug: Abatacept; Participants will receive abatacept at a single dose 750 mg as IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax)	Maximum Observed Serum Concentration	From drug administration to 70 days following drug administration
Area Under the Curve AUC(INF)	Area under the serum concentration-time curve from time zero extrapolated to infinity	From drug administration to 70 days following drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of Maximum Observed Serum Concentration (Tmax)	Time of maximum observed serum concentration	From drug administration to 70 days following drug administration
Area Under the Curve AUC(0-T)	Area under the serum concentration-time curve from zero to the last time of the last quantifiable concentration	From drug administration to 70 days following drug administration
Area Under the Curve AUC(0-28)	Area under the serum concentration-time curve from time zero to 28 days after dosing	From drug administration to 70 days following drug administration
Total Body Clearance (CLT)	Total body clearance	From drug administration to 70 days following drug administration
Volume of Distribution at Steady-State (Vss)	Volume of distribution at steady-state	From drug administration to 70 days following drug administration
Terminal Phase Elimination Half-life (T-HALF)	Terminal phase elimination half-life in serum	From drug administration to 70 days following drug administration
Number of Participants Experiencing Positive Immunogenicity Response to Abatacept	Positive immunogenicity response to Abatacept was defined if one of the following criteria was met: missing baseline immunogenicity measurement and a positive, post-baseline, laboratory-reported immunogenicity response;; a negative laboratory-reported baseline immunogenicity response and a positive, post-baseline, laboratory-reported response;; a positive, laboratory-reported, baseline immunogenicity response and a positive, post-baseline, laboratory-reported immunogenicity response with a titer value greater than the baseline titer value.	From Day 1 (Predose) to Day 71 (Study Discharge), assessed at day 1, day 29, day 57 and day 71
Number of Participants Experiencing Adverse Events	Number of participants experiencing different types of Adverse Events (AEs). Peri-infusional AEs: occurring during the 30 minute study drug infusion period Post-infusional AEs: occurring within 24 hours post drug infusion	From drug administration to 56 days following drug administration
Change From Baseline in Blood Pressure	Mean Change from Baseline in systolic and diastolic blood pressure values	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Heart Rate	Mean Change from Baseline in heart rate values	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Respiration Rate	Mean Change from Baseline in respiration rate values	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Body Temperature	Mean Change from Baseline in body temperature values	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Electrocardiogram (ECG) Parameters	Mean Change from Baseline in ECG parameters, including PR interval, QRS interval, QT interval, and QTC Fridericia	From baseline (last result before start of study medication) to 70 days after start of study medication
Number of Participants Experiencing Clinically Significant Physical Examination Abnormalities	Number of participants experiencing clinically significant physical examination abnormal findings	From the pre-treatment period to 70 days after start of study medication (approximately 100 days)
Change From Baseline in Laboratory Test Results - Hematology 1	Mean Change from Baseline in laboratory test results - Hematology parameters 1	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Laboratory Test Results - Hematology 2	Mean Change from Baseline in laboratory test results - Hematology parameters 2	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Laboratory Test Results - Hematology 3	Mean Change from Baseline in laboratory test results - Hematocrit	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Laboratory Test Results - Chemistry 1	Mean Change from Baseline in laboratory test results - Chemistry parameters 1	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Laboratory Test Results - Chemistry 2	Mean Change from Baseline in laboratory test results - Chemistry parameters 2	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Laboratory Test Results - Chemistry 3	Mean Change from Baseline in laboratory test results - Chemistry parameters 3	From baseline (last result before start of study medication) to 70 days after start of study medication
Change From Baseline in Laboratory Test Results -Hematology and Chemistry 4	Mean Change from Baseline in laboratory test results - hematology and chemistry parameters 4	From baseline (last result before start of study medication) to 70 days after start of study medication

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 9, 2018
• Primary Completion (ACTUAL): April 2, 2019
• Study Completion (ACTUAL): April 2, 2019

Study Registration Dates

• First Submitted: October 18, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (ACTUAL): October 22, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 7, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: IM101-682

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No