Dr. med. Francesco Bonella
Interstitial and Rare Lung Disease Unit
Autoimmune PAP is a rare autoimmune disease with an estimated prevalence of 0.7 per 100,000 [1,2]. It is caused by accumulation of surfactant lipids and proteins in the alveoli, leading to progressive respiratory insufficiency. Spontaneous remissions are rare. Current therapy is whole lung lavage (WLL) but inhaled recombinant human (rh) granulocyte macrophage-colony stimulating factor (GM-CSF) has been reported as an effective, non-invasive medical therapy in a few uncontrolled studies [3,4,5]. In order to provide clinical evidence of the efficacy and safety of inhaled GM-CSF, our group of European and Japanese researchers and treating physicians designed a randomized, double-blind, placebo-controlled, parallel group, international clinical trial (IMPALA, NCT02702180) .
The objective of the trial is to investigate the efficacy and safety of inhaled GM-CSF (molgramostim nebuliser solution; Molgradex®) in the treatment of patients with autoimmune pulmonary alveolar proteinosis. The product used in the trial is molgramostim nebuliser solution (Molgradex®; Savara Pharmaceuticals), which is a liquid formulation containing 300 mcg/dose of molgramostim (E.coli derived rhGM-CSF) and is administered using a vibrating mesh nebuliser (PARI eFlow®; PARI Pharma, Germany).
Up to 51 patients will be included at approximately 18 sites in Europe, Russia, Israel and Japan. Adult patients with PAP should fulfil the key inclusion criteria of:
Patients are randomised to once daily treatment for 24 weeks with: 1) inhaled rhGM-CSF (300 µg); 2) inhaled rhGM-CSF (300 µg) or placebo administered intermittently (7 days on/7 days off); or 3) inhaled placebo. After the double-blind period, patients enter an open-label follow-up period, where inhaled rhGM-CSF may be given at the intermittent regimen (7 days on/7 days off). WLL will be used as rescue therapy throughout the trial.
The primary endpoint is the change from baseline in (A-a)DO2 after 24-weeks treatment. Secondary endpoints include number of patients needing WLL, time to WLL, change from baseline in pulmonary functions tests, 6MWT, symptom scores, quality of life and HR-CT scoring.
Since the IMPALA trial is the first RCT for the treatment of aPAP, we encourage you to contact the nearest trial site or the trial sponsor if you have a PAP patient that may be eligible. The achievement of an approved drug for this neglected disease is a highly-awaited goal for PAP patients and their treating physicians.