Clinical trial NCT02077465: Safety, Tolerability, and Pharmacokinetics of Andecaliximab in Adults With Chronic Obstructive Pulmonary Disease (COPD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD, chronic obstructive pulmonary disease; Safety, Pharmacokinetics
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-03-04
Enrollment: 11
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: First dose date up to Day 29 plus 30 days
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to Day 29 plus 30 days
measure: Percentage of Participants Who Developed Anti-andecaliximab Antibodies
timeFrame: Day 43
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter of Andecaliximab: AUClast for Days 1, 15 and 29
timeFrame: 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
measure: PK Parameter of Andecaliximab: AUCinf for Day 1
timeFrame: 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
measure: PK Parameter of Andecaliximab: %AUCexp for Day 1
timeFrame: 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
measure: PK Parameter of Andecaliximab: Cmax for Days 1, 15 and 29
timeFrame: 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
measure: PK Parameter of Andecaliximab: Tmax for Days 1, 15 and 29
timeFrame: 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
measure: PK Parameter of Andecaliximab: Clast for Days 1, 15 and 29
timeFrame: 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
measure: PK Parameter of Andecaliximab: Tlast for Days 1, 15 and 29
timeFrame: 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
measure: PK Parameter of Andecaliximab: λz for Day 1
timeFrame: 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
measure: PK Parameter of Andecaliximab: CL for Day 1
timeFrame: 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
measure: PK Parameter of Andecaliximab: Vz for Day 1
timeFrame: 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
measure: PK Parameter of Andecaliximab: Vss for Day 1
timeFrame: 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
measure: PK Parameter of Andecaliximab: t1/2 for Day 1
timeFrame: 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
Other outcomes:
Locations:
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
city: Miami
country: United States
facility: Elite Research Institute
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Buffalo
country: United States
facility: University at Buffalo CTRC
state: New York
city: Knoxville
country: United States
facility: Volunteer Research Group
state: Tennessee
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: