Cystic Fibrosis
Conditions
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.
Interventions
DRUGAndecaliximab
Administered via subcutaneous injection
DRUGPlacebo
Administered via subcutaneous injection
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Absolute Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 | Baseline; Week 8 |
Secondary
| 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 |
Countries
Australia, France, Germany, Spain, United Kingdom
Participant flow
Recruitment details
Participants were enrolled at study sites in Australia and Europe. The first participant was screened on 04 November 2016. The last study visit occurred on 21 July 2017. The study was terminated after 6 participants were enrolled in Part 1 of the study. Therefore, Part 2 was not initiated.
Pre-assignment details
26 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Andecaliximab Double-Blind Period: Andecaliximab 600 mg administered via subcutaneous injection weekly for 8 weeks
Open-Label Period: Andecaliximab 600 mg administered via subcutaneous injection weekly for up to 16 weeks | 3 |
| Placebo Double-Blind Period: Placebo administered via subcutaneous injection weekly for 8 doses
Open-Label Period: Andecaliximab 600 mg administered via subcutaneous injection weekly for up to 16 weeks | 3 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open-Label Treatment Period | Study Terminated by Sponsor | 1 | 2 |
| Open-Label Treatment Period | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Andecaliximab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 46.0 years STANDARD_DEVIATION 20.42 | 43.3 years STANDARD_DEVIATION 10.02 | 44.7 years STANDARD_DEVIATION 14.46 |
| Post-bronchodilator FEV1 % predicted | 52.1 percent STANDARD_DEVIATION 5.9 | 64.6 percent STANDARD_DEVIATION 20.58 | 58.3 percent STANDARD_DEVIATION 15.17 |
| Pre-bronchodilator Forced expiratory volume in 1 second (FEV1) % predicted | 49.7 percent STANDARD_DEVIATION 8.7 | 59.1 percent STANDARD_DEVIATION 19.26 | 54.4 percent STANDARD_DEVIATION 14.33 |
| Race/Ethnicity, Customized Not Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment Australia | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment France | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Germany | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Spain | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 4 |
Outcome results
Primary
Absolute Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8
Time frame: Baseline; Week 8
Population: Full Analysis Set: all randomized participants who took at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | Absolute Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 | -2.10 percent | Standard Deviation 4.446 |
| Placebo | Absolute Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 | 2.90 percent | Standard Deviation 3.461 |
Secondary
Absolute Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8
Time frame: Baseline; Week 8
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | Absolute Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 | 1.01 percent | Standard Deviation 4.534 |
| Placebo | Absolute Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 | -1.45 percent | Standard Deviation 1.655 |
Secondary
Relative Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8
Time frame: Baseline; Week 8
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | Relative Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 | 2.28 percent change | Standard Deviation 9.323 |
| Placebo | Relative Change in Post-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 | -1.98 percent change | Standard Deviation 1.749 |
Secondary
Relative Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8
Time frame: Baseline; Week 8
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | Relative Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 | -3.85 percent change | Standard Deviation 9.009 |
| Placebo | Relative Change in Pre-bronchodilator FEV1 Percent Predicted From Baseline to Week 8 | 4.41 percent change | Standard Deviation 4.196 |