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

NCT02077465 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GS-US-368-1212
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD, chronic obstructive pulmonary disease; Safety, Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (12)

• 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: 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

• 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: 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

Study Arms (2)

Andecaliximab

EXPERIMENTAL

Participants will receive andecaliximab every 2 weeks for a total of 3 infusions.

Drug: Andecaliximab

Placebo to match andecaliximab

PLACEBO COMPARATOR

Participants will receive placebo to match andecaliximab every 2 weeks for a total of 3 infusions.

Drug: Placebo to match Andecaliximab

Interventions

Andecaliximab DRUG

400 mg andecaliximab administered intravenously

Also known as: GS-5745

Andecaliximab

Placebo to match Andecaliximab DRUG

Placebo to match andecaliximab administered intravenously

Placebo to match andecaliximab

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (5)

Advanced Pharma CR, LLC

Miami, Florida, 33136, United States

Location

Elite Research Institute

Miami, Florida, 33169, United States

Location

Compass Research, LLC

Orlando, Florida, 32806, United States

Location

University at Buffalo CTRC

Buffalo, New York, 14203, United States

Location

Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

andecaliximab

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2014
• First Posted: March 4, 2014
• Study Start: March 11, 2014
• Primary Completion: October 27, 2014
• Study Completion: October 27, 2014
• Last Updated: September 9, 2020
• Results First Posted: August 13, 2020

Record last verified: 2020-08

Locations

US (5)