NCT02077465已完成1 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 5
- 主要终点
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Andecaliximab
Experimental
Participants will receive andecaliximab every 2 weeks for a total of 3 infusions.
干预措施: Andecaliximab (Drug)
Placebo to match andecaliximab
Placebo Comparator
Participants will receive placebo to match andecaliximab every 2 weeks for a total of 3 infusions.
干预措施: Placebo to match Andecaliximab (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
时间窗: First dose date up to Day 29 plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
时间窗: 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.
Percentage of Participants Who Developed Anti-andecaliximab Antibodies
时间窗: 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.
次要结局
- PK Parameter of Andecaliximab: AUCinf for Day 1(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)
- Pharmacokinetic (PK) Parameter of Andecaliximab: AUClast for Days 1, 15 and 29(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: %AUCexp for Day 1(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(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(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(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(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(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(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(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(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(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)
研究者
研究点 (5)
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