Effect of Andecaliximab on FEV1 in Adults With Cystic Fibrosis

• Andecaliximab (Drug), also known as GS-5745: Administered via subcutaneous injection
• Placebo (Drug): Administered via subcutaneous injection

Primary outcomes

• Absolute Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 [Baseline; Week 8]

Secondary outcomes

• 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]

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Absolute Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 (Primary), Mean, percent: Andecaliximab -2.10 +/- 4.446; Placebo 2.90 +/- 3.461
• Absolute Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 (Secondary), Mean, percent: Andecaliximab 1.01 +/- 4.534; Placebo -1.45 +/- 1.655
• Relative Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 (Secondary), Mean, percent change: Andecaliximab -3.85 +/- 9.009; Placebo 4.41 +/- 4.196
• Relative Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 (Secondary), Mean, percent change: Andecaliximab 2.28 +/- 9.323; Placebo -1.98 +/- 1.749

Adverse events

Time frame: Baseline up to the last dose date plus 30 days (maximum exposure: 140 days)

Other adverse events by term

Limitations and caveats: Gilead made a decision to discontinue the development of andecaliximab in cystic fibrosis. This decision was not due to any safety concerns. Because only 6 participants were enrolled, no inferential analyses were performed.

• Study Protocol: Original (PDF, 2016-01-14)
• Study Protocol: Amendment 2 (PDF, 2016-05-25)
• Statistical Analysis Plan (PDF, 2017-09-05)

• Gilead Study Director, Study director, Gilead Sciences

NIH grants: 2015