Effect of Andecaliximab on FEV1 in Adults With Cystic Fibrosis

Phase 2

Terminated

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Andecaliximab 300 mg (Part 2)	Andecaliximab	Andecaliximab 300 mg weekly for 8 weeks
Placebo (Part 2)	Placebo	Placebo weekly for 8 weeks
Open-Label Extension	Andecaliximab	(Part 1) Andecaliximab 600 mg weekly for 16 weeks; (Part 2) Andecaliximab 300 mg weekly for 16 weeks
Andecaliximab 600 mg (Part 1)	Andecaliximab	Andecaliximab 600 mg weekly for 8 weeks
Andecaliximab 150 mg (Part 2)	Andecaliximab	Andecaliximab 150 mg + placebo weekly for 8 weeks
Placebo (Part 1)	Placebo	Placebo weekly for 8 weeks
Andecaliximab 150 mg (Part 2)	Placebo	Andecaliximab 150 mg + placebo weekly for 8 weeks

Primary Outcome Measures

Name	Time	Method
Absolute Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8	Baseline; Week 8

Secondary Outcome Measures

Name	Time	Method
Relative Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8	Baseline; Week 8
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