Table 2.
Inhaled rhu GM-CSF phase 2-3 clinical studies in aPAP.
| Study | Study design | rhu GM-CSF treatment | Results |
|---|---|---|---|
| Trapnell et al. (38) 2020 |
Prospective, randomized trial (N=138) | Molgramostim 300 μg inhaled daily, continuous or intermittently (every other week) x 24 weeks or placebo | Continuous molgramostim vs placebo: • Primary endpoint: Δ P(A-a)O2 from baseline: −12.8 mmHg vs −6.6 mmHg (p=0.03) o Δ in % predicted DLCO: 12.0 vs 4.2 o Δ SGRQ total score: -12.4 points vs -5.1 points |
| Tazawa et al. (39) 2019 |
Prospective, phase 2, randomized trial (N=64) | Sargramostim 125 μg inhaled twice daily x 7 days, every other week x 24 weeks or placebo | Sargramostim vs placebo: • Primary endpoint: Δ P(A-a)O2 from baseline: −4.50 mm Hg vs 0.17 mm Hg (p=0.02) • Δ in % predicted DLCO: 4.70 vs 0.37 • Δ CT density values: –22.4 HUs vs –2.5 HUs |
| Campo et al. (40, 41) 2016 |
Prospective, phase 2, randomized trial (N=18) | WLL followed by inhaled sargramostim 250 μg inhaled daily every other week x 12 weeks, then 250 μg daily x 2 consecutive days every 2 weeks x 6 months or WLL alone | Sargramostim + WLL, improvement at 30 months vs WLL alone • Significant improvement reported in sargramostim + WLL arm: (all (p<0.001): o Increased DLCO%: 15.7 o Increased FVC%: 11.8 o Increased TLC%: 10 o Increased FEV1%: 9.6 o Improved PaO2: 13.7 mmHg o Improved P(A-a)O2: -13.5 mmHg |
| Tazawa et al. (42) 2014 |
Prospective, phase 2, observational trial (N=35) | Long-term (30 month) follow up of Tazawa et al., 2010 study | Free from additional treatment vs additional treatment • Mean % predicted VC: 85.9 vs 71.6 (p=0.0045) • Mean % predicted FVC: 85.3 vs 71.4 (p=0.0064) • 23/35 patients did not require additional treatments • Median time to additional treatments (n=12): 50.5 weeks |
| Tazawa et al. (43) 2010 |
Prospective, phase 2, crossover, self-controlled, open-label trial (N=50) | • Observation period x 12 weeks • Sargramostim High dose period: 125 μg inhaled twice daily on days 1–8, no therapy on days 9–14 x six 2-week cycles (induction therapy) • Sargramostim Low dose period: 125 μg inhaled daily on days 1–4, no therapy on days 5–14 x six 2-week cycles (maintenance therapy) |
Before vs after sargramostim therapy (observation vs high-dose induction + low-dose maintenance): • Primary endpoint: Δ P(A-a)O2 from baseline: -12.3 mmHg (p<0.0001) • Mean % predicted DLCO: 53.7 vs 61.4 (p=0.0008) • 6-min walk test: 393 meters vs 444 meters (p=0.0046) |
DLCO, diffusing capacity of the lungs for carbon monoxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; CT, computed tomography; HUs, Hounsfield units; PaO2, partial pressure of oxygen; P(A-a) O2, alveolar arterial oxygen gradient; SGRQ, ST. George’s Respiratory Questionnaire; TLC, total lung capacity; VC, vital capacity; WLL, whole lung lavage.