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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Andecaliximab; Drug: Placebo to match Andecaliximab

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33169
      • Elite Research Institute
    • Miami, Florida, United States, 33136
      • Advanced Pharma Cr, Llc
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
  • New York
    • Buffalo, New York, United States, 14203
      • University at Buffalo CTRC
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Treatment-Emergent Adverse Events		First dose date up to Day 29 plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	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.	First dose date up to Day 29 plus 30 days
Percentage of Participants Who Developed Anti-andecaliximab Antibodies	The presence of anti-andecaliximab antibodies in serum samples was determined using an electrochemiluminescent (ECL) assay that detects antibodies that bind to andecaliximab.	Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter of Andecaliximab: AUClast for Days 1, 15 and 29	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.	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
PK Parameter of Andecaliximab: AUCinf for Day 1	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.	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
PK Parameter of Andecaliximab: %AUCexp for Day 1	%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.	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
PK Parameter of Andecaliximab: Cmax for Days 1, 15 and 29	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.	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
PK Parameter of Andecaliximab: Tmax for Days 1, 15 and 29	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.	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
PK Parameter of Andecaliximab: Clast for Days 1, 15 and 29	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.	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
PK Parameter of Andecaliximab: Tlast for Days 1, 15 and 29	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.	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
PK Parameter of Andecaliximab: λz for Day 1	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.	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
PK Parameter of Andecaliximab: CL for Day 1	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.	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
PK Parameter of Andecaliximab: Vz for Day 1	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.	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
PK Parameter of Andecaliximab: Vss for Day 1	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.	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
PK Parameter of Andecaliximab: t1/2 for Day 1	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.	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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2014
• Primary Completion (Actual): October 27, 2014
• Study Completion (Actual): October 27, 2014

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: March 3, 2014
• First Posted (Estimate): March 4, 2014

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: August 21, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: COPD, chronic obstructive pulmonary disease; Safety, Pharmacokinetics
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: GS-US-368-1212

Drug and device information, study documents

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