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

Phase 1CompletedNCT02077465

Gilead Sciences11 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Chronic Obstructive Pulmonary Disease

Interventions

AndecaliximabDRUG

400 mg andecaliximab administered intravenously

Placebo to match AndecaliximabDRUG

Placebo to match andecaliximab administered intravenously

Eligibility

Sex: ALLMin age: 40 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (5)

Advanced Pharma CR, LLC

Miami, Florida, United States

Elite Research Institute

Miami, Florida, United States

Compass Research, LLC

Orlando, Florida, United States

University at Buffalo CTRC

Buffalo, New York, United States

Outcomes

Primary Outcomes

Percentage of Participants Experiencing Treatment-Emergent Adverse Events

Time frame: 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.

Time frame: 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.

Time frame: Day 43

Secondary Outcomes

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.

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

PK Parameter of Andecaliximab: AUCinf for Day 1

Data from ClinicalTrials.gov

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