Effect of Andecaliximab on FEV1 in Adults With Cystic Fibrosis

A Phase 2b, Dose-Ranging Study of the Effect of GS-5745 on FEV1 in Adult Subjects With Cystic Fibrosis

The primary objective of this study is to evaluate the effect of andecaliximab (GS-5745) on pre-bronchodilator forced expiratory volume in 1 second (FEV1) % predicted in adults with cystic fibrosis (CF) after 8 weeks of treatment.

There will be 2 parts to this study. In Part 1, andecaliximab 600 mg or placebo will be administered for 8 weeks. In Part 2, andecaliximab 300 mg, 150 mg, or placebo will be administered for 8 weeks. Part 2 will be initiated after completion of Part 1.

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: Andecaliximab

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • New Lambton, New South Wales, Australia
• France
  • Montpellier, France
• Germany
  • Berlin, Germany
• Spain
  • Barcelona, Spain
• United Kingdom
  • Liverpool, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Confirmed diagnosis of CF as determined by the 2008 Cystic Fibrosis Foundation Consensus Report criteria
• Must have a body weight of > 40 kg (88.2 lb) at study screening
• Pre-bronchodilator FEV1 ≥ 40% and ≤ 80% of predicted at screening

• Two pre-bronchodilator spirometry measures during screening and baseline must meet the following 2 criteria:

  • The relative difference of FEV1(L), calculated as the absolute value of [(first FEV1 - second FEV1) / first FEV1] x 100 should be < 12% AND
  • The absolute difference in FEV1 should be < 200 ml
• Negative Sputum Investigation/History of any Mycobacterium spp. or Burkholderia spp. per specified protocol-defined time periods
• Clinically stable with no evidence of significant respiratory symptoms that would require administration of IV antibiotics, oxygen supplementation, or hospitalization within 30 days of baseline.
• On stable CF chronic medical regimen for at least 30 days prior to baseline and expected to remain stable through the completion of the study. This includes but is not limited to: chronic azithromycin use, inhaled bronchodilators, inhaled corticosteroids, inhaled dornase alpha, inhaled hypertonic saline, inhaled mannitol, ivacaftor, and/or ivacaftor/lumacaftor.

Key Exclusion Criteria:

• Concurrent use of oral antibiotics (excluding chronic azithromycin use) or IV antibiotics within 30 days of baseline. Prophylactic and chronic doxycycline use is prohibited during the study.
• Hospitalization for a respiratory event within 30 days of baseline
• Current use of systemic immunosuppressive drugs including oral corticosteroids within 30 days of Baseline
• Current requirement for daily continuous oxygen supplementation or requirement (medically necessary) of more than 2 L/minute at night (subject would not meet this exclusion criterion if supplemental oxygen is used for comfort only)
• History of solid organ (including lung) or hematologic transplant, or currently on a transplant waiting list

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Andecaliximab 600 mg (Part 1); Andecaliximab 600 mg weekly for 8 weeks	Drug: Andecaliximab; Administered via subcutaneous injection; Other Names: GS-5745
Placebo Comparator: Placebo (Part 1); Placebo weekly for 8 weeks	Drug: Placebo; Administered via subcutaneous injection
Experimental: Andecaliximab 300 mg (Part 2); Andecaliximab 300 mg weekly for 8 weeks	Drug: Andecaliximab; Administered via subcutaneous injection; Other Names: GS-5745
Experimental: Andecaliximab 150 mg (Part 2); Andecaliximab 150 mg + placebo weekly for 8 weeks	Drug: Placebo; Administered via subcutaneous injection; Drug: Andecaliximab; Administered via subcutaneous injection; Other Names: GS-5745
Placebo Comparator: Placebo (Part 2); Placebo weekly for 8 weeks	Drug: Placebo; Administered via subcutaneous injection
Experimental: Open-Label Extension; (Part 1) Andecaliximab 600 mg weekly for 16 weeks; (Part 2) Andecaliximab 300 mg weekly for 16 weeks	Drug: Andecaliximab; Administered via subcutaneous injection; Other Names: GS-5745

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8	Baseline; Week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Absolute Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8	Baseline; Week 8
Relative Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8	Baseline; Week 8
Relative Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8	Baseline; Week 8

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2016
• Primary Completion (Actual): July 6, 2017
• Study Completion (Actual): July 21, 2017

Study Registration Dates

• First Submitted: April 29, 2016
• First Submitted That Met QC Criteria: April 29, 2016
• First Posted (Estimate): May 3, 2016

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: July 20, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: GS-US-404-1808; 2015-002192-23 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No