Effect of Andecaliximab on FEV1 in Adults With Cystic Fibrosis

Study Overview
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Brief Summary
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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.

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

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Andecaliximab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |