Safety, Tolerability, and Pharmacokinetics of Andecaliximab in Adults With Chronic Obstructive Pulmonary Disease (COPD)
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Andecaliximab; Placebo to match Andecaliximab
Intervention description: 400 mg andecaliximab administered intravenously; Placebo to match andecaliximab administered intravenously
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: COPD, chronic obstructive pulmonary disease; Safety, Pharmacokinetics

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.
    

Eligibility 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.