Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (IMPALA)
Autoimmune Pulmonary Alveolar Proteinosis
About this trial
This is an interventional treatment trial for Autoimmune Pulmonary Alveolar Proteinosis
Eligibility Criteria
Inclusion Criteria:
- aPAP diagnosed by computed tomography, or by biopsy, or by Broncho Alveolar Lavage (BAL), and by increased GM-CSF autoantibodies in serum.
- Stable or progressive aPAP during a minimum period of 2 months prior to the Baseline visit.
- Arterial oxygen tension (PaO2) <75 mmHg/<10 kilo Pascal (kPa) at rest, OR desaturation of >4 percentage points on the 6MWT
- An alveolar-arterial oxygen difference [(A-a)DO2] of minimum 25 mmHg/3.33 kPa
- Female or male ≥18 years of age
- Females who have been post-menopausal for >1 year or females of childbearing potential after a confirmed menstrual period using a highly efficient method of contraception (i.e. a method with <1% failure rate such as combined hormonal contraception, progesterone-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence), during and until 30 days after last dose of double-blind trial treatment. Females of childbearing potential must have a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at dosing at Baseline (Visit 2) and must not be lactating
- Males agreeing to use condoms during and until 30 days after last dose of double-blind medication, or males having a female partner who is using adequate contraception as described above
- Willing and able to provide signed informed consent
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures specified in the protocol as judged by the investigator
Exclusion Criteria:
- Diagnosis of hereditary or secondary PAP
- WLL within 1 month of Baseline
- Treatment with GM-CSF within 3 months of Baseline
- Treatment with rituximab within 6 months of Baseline
- Treatment with plasmapheresis within 3 months of Baseline
- Treatment with any investigational medicinal product within 4 weeks of Screening
- Concomitant use of sputum modifying drugs such as carbocysteine or ambroxol
- History of allergic reactions to GM-CSF
- Connective tissue disease, inflammatory bowel disease or other autoimmune disorder requiring treatment associated with significant immunosuppression, e.g. more than 10 mg/day systemic prednisolone
- Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product
- History of, or present, myeloproliferative disease or leukaemia
- Known active infection (viral, bacterial, fungal or mycobacterial)
- Apparent pre-existing concurrent pulmonary fibrosis
- Any other serious medical condition which in the opinion of the investigator would make the participant unsuitable for the trial
Sites / Locations
- UCLA
- University of Florida
- Cincinnati Children's Hospital Medical Center
- Royal Prince Alfred Hospital
- Aarhus University Hospital
- CHU Rennes Hospital Pontchaillou
- Westdeutsches Lungenzentrum am Universitätsklinikum Essen
- Asklepios Fachkliniken München - Gauting
- Thoraxklinik am Universitätsklinikum Heidelberg
- Universitätsklinikum Schleswig-Holstein Zentralklinikum, Lübeck Medizinische Klinik III, Pneumologie
- Attikon University Hospital
- Rabin Medical Center
- IRCCS Policlinico San Matteo
- Niigata University Medical and Dental Hospital
- National Hospital Organization Kinki-Chuo
- Tohoku University Hospital
- Aichi Medical University Hospital
- Kanagawa Cardiovascular and Respiratory Center
- Seoul National University Hospital
- Asan Medical Center, Division of Pulmonary and Critical Care Medicine
- Samsung Medical Center, Division of Pulmonary and Critical Care Medicine
- St. Antonius Hospital
- Hospital de dia de Pneumologia
- Hospital Sao Joao
- City Hospital St. Petersburg
- II. Pulmonary Department National Institut for TB, Lung Diseases and Chest Surgery
- Hospital University de Bellvitge (HUB)
- Centre Hospitalier Universitaire Vaudois
- Yedikule Pulmonary Diseases and Pulmonary Surgery Training and Research Hospital
- Royal Brompton Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Placebo Comparator
Experimental
Double-blind molgramostim once daily
Double-blind molgramostim intermittent
Double-blind placebo
Open-label molgramostim intermittent
Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks
Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles)
Inhalation of placebo nebuliser solution once daily for 24 weeks
Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 or 48 weeks from completion of the double-blind period