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Safety, Tolerability, and Pharmacokinetics of Andecaliximab in Adults With Chronic Obstructive Pulmonary Disease (COPD)

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ClinicalTrials.gov Identifier: NCT02077465
Recruitment Status : Completed
First Posted : March 4, 2014
Results First Posted : August 13, 2020
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objective of the study is to assess the safety and tolerability of multiple infusions of andecaliximab (formerly GS-5745) in participants with chronic obstructive pulmonary disease (COPD) as assessed by adverse events (AEs) and laboratory abnormalities.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: Andecaliximab Drug: Placebo to match Andecaliximab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1 Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GS-5745 in Subjects With Chronic Obstructive Pulmonary Disease
Actual Study Start Date : March 11, 2014
Actual Primary Completion Date : October 27, 2014
Actual Study Completion Date : October 27, 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Andecaliximab
Participants will receive andecaliximab every 2 weeks for a total of 3 infusions.
Drug: Andecaliximab
400 mg andecaliximab administered intravenously
Other Name: GS-5745

Placebo Comparator: Placebo to match andecaliximab
Participants will receive placebo to match andecaliximab every 2 weeks for a total of 3 infusions.
Drug: Placebo to match Andecaliximab
Placebo to match andecaliximab administered intravenously




Primary Outcome Measures :
  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: First dose date up to Day 29 plus 30 days ]
  2. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities [ Time Frame: First dose date up to Day 29 plus 30 days ]
    A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline and occurring after the first dose of study drug and within 30 days after last study drug administration. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The most severe graded abnormality from all tests was counted for each participant.

  3. Percentage of Participants Who Developed Anti-andecaliximab Antibodies [ Time Frame: Day 43 ]
    The presence of anti-andecaliximab antibodies in serum samples was determined using an electrochemiluminescent (ECL) assay that detects antibodies that bind to andecaliximab.


Secondary Outcome Measures :
  1. Pharmacokinetic (PK) Parameter of Andecaliximab: AUClast for Days 1, 15 and 29 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes ]
    AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.

  2. PK Parameter of Andecaliximab: AUCinf for Day 1 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes ]
    AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.

  3. PK Parameter of Andecaliximab: %AUCexp for Day 1 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes ]
    %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.

  4. PK Parameter of Andecaliximab: Cmax for Days 1, 15 and 29 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes ]
    Cmax is defined as the maximum observed plasma concentration of drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.

  5. PK Parameter of Andecaliximab: Tmax for Days 1, 15 and 29 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes ]
    Tmax is defined as the time (observed time point) of Cmax. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.

  6. PK Parameter of Andecaliximab: Clast for Days 1, 15 and 29 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes ]
    Clast is defined as the last observable concentration of drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.

  7. PK Parameter of Andecaliximab: Tlast for Days 1, 15 and 29 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes ]
    Tlast is defined as the time (observed time point) of Clast. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.

  8. PK Parameter of Andecaliximab: λz for Day 1 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes ]
    λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.

  9. PK Parameter of Andecaliximab: CL for Day 1 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes ]
    Clearance (CL) is defined as the systemic clearance of the drug following intravenous administration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.

  10. PK Parameter of Andecaliximab: Vz for Day 1 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes ]
    Vz is defined as the volume of distribution of the drug after intravenous administration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.

  11. PK Parameter of Andecaliximab: Vss for Day 1 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes ]
    Vss is defined as the volume of distribution of the drug at steady state after intravenous administration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.

  12. PK Parameter of Andecaliximab: t1/2 for Day 1 [ Time Frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes ]
    t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Weight: ≥ 45 kg to < 120 kg at screening
  • Males or non-pregnant, non-lactating females
  • Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception. Male individuals must refrain from sperm donation for 90 days post last infusion of the study drug
  • Diagnosis of COPD per Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for at least 6 months prior to screening and anticipated to remain on stable therapy for the duration of the study
  • Post-bronchodilator forced expiratory volume in one second (FEV1) ≥ 40% predicted
  • No changes in COPD medications within 30 days prior to randomization
  • Hepatic panel [aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH)] ≤ 2 times the upper limit of the normal range (ULN)
  • Serum creatinine ≤ 2.0
  • Hemoglobin ≥ 8.5 g/dL (both males and females)
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1,500 mm^3)
  • Platelets ≥ 100 x 10^9/L

Key Exclusion Criteria:

  • Clinically significant active infection as judged by the investigator during screening
  • Known history of HIV, hepatitis B or C during screening. Individuals who are hepatitis B surface antigen positive, but who received a successful series of hepatitis B vaccinations and never had the disease remain eligible
  • A positive QuantiFERON-TB GOLD test during screening
  • History of malignancy within the last 5 years except for patients who have been treated locally for non-melanoma skin cancer or cervical carcinoma in situ
  • Any serious cardiac event such as myocardial infarction, unstable or life-threatening arrhythmia, hospitalization for cardiac failure within 6 months prior to randomization or any significant or new electrocardiogram (ECG) finding at Visit 1 as judged by the Investigator
  • A hospitalization for a respiratory event such as, but not limited to, COPD, pneumonia, bronchiolitis, within the previous 6 months prior to randomization
  • Chronic lung disease other than COPD such as: asthma, cystic fibrosis or fibrotic disease, α-1-antitrypsin deficiency, interstitial lung disease, pulmonary thromboembolic disease, or bronchiectasis
  • Chronic use of systemic corticosteroids and/or treatment with systemic corticosteroids for an acute exacerbation of COPD (AECOPD) event, or other medical condition not requiring hospitalization, within 90 days of randomization.
  • Treatment with antibiotics for an AECOPD event, or other medical condition not requiring hospitalization within 90 days of randomization, or any minor medical event not requiring hospitalization within 14 days of randomization.
  • Treatment with any marketed or investigational biologic within 5 half-lives of the molecule or if unknown within 90 days of screening
  • Individuals currently on nonbiologic immune modulator medications such as: azathioprine, cyclosporine, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil, sulfasalazine, tofacitinib, within 90 days of randomization

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02077465


Locations
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United States, Florida
Advanced Pharma CR, LLC
Miami, Florida, United States, 33136
Elite Research Institute
Miami, Florida, United States, 33169
Compass Research, LLC
Orlando, Florida, United States, 32806
United States, New York
University at Buffalo CTRC
Buffalo, New York, United States, 14203
United States, Tennessee
Volunteer Research Group
Knoxville, Tennessee, United States, 37920
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02077465    
Other Study ID Numbers: GS-US-368-1212
First Posted: March 4, 2014    Key Record Dates
Results First Posted: August 13, 2020
Last Update Posted: September 9, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
COPD, chronic obstructive pulmonary disease; Safety, Pharmacokinetics
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs