160 subjects with autoimmune pulmonary alveolar proteinosis (aPAP) will be randomized to receive once daily treatment with inhaled molgramostim (MOL) or placebo (PBO) for 48 weeks. Subjects completing the 48-week placebo-controlled period will receive open-label treatment with once daily inhaled molgramostim for 96 weeks.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Subject must be ≥18 years of age, at the time of signing the informed consent (≥20 in Japan).
2. A serum anti-GM-CSF autoantibody test result confirming autoimmune PAP.
3. History of PAP, based on examination of a lung biopsy, bronchoalveolar lavage (BAL) cytology, or a high-resolution computed tomogram (HRCT) of the chest.
4. A diffusing capacity for carbon monoxide of 70% predicted or lower adjusted for hemoglobin (%DLCOadj) at the screening and baseline visits.
5. Change in %DLCO adj of \<15% points during the screening period.
6. Demonstrated functional impairment in the treadmill exercise test (defined as a peak metabolic equivalent (MET) ≤8).
7. Willing and able to come off supplemental oxygen use prior to and during the treadmill exercise test, the DLCO assessment, and the arterial blood gas sampling.
8. Resting oxygen saturation (SpO2) \>85% during 15 minutes without use of supplemental oxygen at the screening visits.
9. Male or female
10. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
1. Male subjects: Males agreeing to use condoms during and until 30 days after last dose of trial treatment, or males having a female partner who is using adequate contraception as described below.
2. Female subjects: 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, vasectomized partner, sexual abstinence\*), during and until 30 days after last dose of trial treatment. Females of childbearing potential must have a negative serum pregnancy test at the screening visits, and a negative urine pregnancy test at Baseline visit (Visit 3) and must not be lactating.
11. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
12. 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:
1. Diagnosis of hereditary or secondary PAP, or a metabolic disorder of surfactant production.
2. Whole lung lavage (WLL) performed within 3 months prior to baseline.
3. Requirement for WLL at screening or baseline.
4. GM-CSF treatment within 6 months prior to baseline.
5. Treatment with rituximab within 6 months prior to baseline.
6. Treatment with plasmapheresis within 6 weeks prior to baseline.
7. Treatment with any investigational medicinal product within 5 half-lives or 3 months (whichever is longer) prior to baseline.
8. Previously randomized in this trial.
9. History of allergic reactions to GM-CSF or any of the excipients in the nebulizer solution.
10. Inflammatory or autoimmune disease of a severity that necessitates significant (e.g. more than 10 mg/day systemic prednisolone) immunosuppression.
11. Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product.
12. History of, or present, myeloproliferative disease or leukemia.
13. Apparent pre-existing concurrent pulmonary fibrosis.
14. Acute or unstable cardiac or pulmonary disease that may be aggravated by exercise.
15. Known active infection (viral, bacterial, fungal, or mycobacterial) that may affect the efficacy evaluation in the trial.
16. Physical disability or other condition that precludes safe and adequate exercise testing.
17. Any other serious medical condition which in the opinion of the Investigator would make the subject unsuitable for the trial.
18. Pregnant, planning to become pregnant during the trial, or breastfeeding woman. For France only: including as further defined by French Health Code L-1121-5.
19. For France only: Any subject considered to be "vulnerable" on account of, e.g., mental or physical disability, socio-economic situation, or subjects deprived of their liberty. For France only: including as further defined by French Health Code L1121-8-1.
Primary outcome measure(s)
Change From Baseline in Percent (%) Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted for Hemoglobin Concentration to Week 24 — From Baseline to Week 24 As a measure of pulmonary gas transfer, a standardized lung function test, DLCO, was conducted. The single-breath DLCO test was performed in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines for DLCO testing. Results reported as % predicted DLCO adjusted for hemoglobin concentration (%predicted DLCOadj).
Trial sites (54)
Facility
City
Region
Status
University Of Arkansas For Medical Services
Little Rock
Arkansas
UCLA David Geffen School of Medicine
Los Angeles
California
National Jewish Health
Denver
Colorado
Yale University
New Haven
Connecticut
University of Florida Health
Gainesville
Florida
Emory University
Atlanta
Georgia
Loyola University
Maywood
Illinois
University of Maryland Medical Center
Baltimore
Maryland
Washington University in St. Louis
St Louis
Missouri
Duke University Medical Center
Durham
North Carolina
Wake Med Health & Hospital
Raleigh
North Carolina
Cincinnati Children's Hospital Medical Center
Cincinnati
Ohio
Cleveland Clinic
Cleveland
Ohio
University of Pennsylvania Perelman School of Medicine - Pulmonology
Philadelphia
Pennsylvania
University of Pittsburgh
Pittsburgh
Pennsylvania
UT Southwestern Medical Center
Dallas
Texas
Royal Prince Alfred Hospital
Camperdown
New South Wales
Westmead Hospital
Westmead
New South Wales
Hôpital Erasme
Brussels
Brussels Capital
UZ Leuven - Campus Gasthuisberg - Pneumologie
Leuven
Vlaams Brabant
University of Calgary
Calgary
Alberta
St Joseph's Healthcare Hamilton Research
Hamilton
Ontario
University Institute of Cardiology and Respirology of Quebec
Québec
Quebec
Hôpital Louis Pradel
Bron
Auvergne-Rhône-Alpes
CHU Pontchaillou
Rennes
Brittany Region
Thoraxklinik Heidelberg gGmbH am Universitätsklinikum Heidelberg
Heidelberg
Baden-Wurttemberg
Asklepios Fachkliniken Muenchen-Gauting
Muenchen-Gauting
Bavaria
Ruhrlandklinik Westdeutsches Lungenzentrum
Essen
North Rhine-Westphalia
Attikon University Hospital
Athens
Greece
St. Vincent's University Hospital
Dublin
Ireland
Fondazione IRCCS Policlinico San Matteo
Pavia
Lombardy
Chiba University Hospital - Respiratory Medicine
Chiba
Chiba
Hokkaido University Hospital
Sapporo
Hokkaidô
Kanagawa Cardiovascular and Respiratory Center
Yokohama
Kanagawa
Kumamoto University Hospital
Kumamoto
Kumamoto
Tohoku University Hospital - Respiratory Tract Medicine
Sendai
Miyagi
National Hospital Organization Kinki-Chuo Chest medical Center
Sakai
Osaka
Saitama Red Cross Hospital
Saitama
Saitama
Kyorin University Hospital
Mitaka
Tokyo
Aichi Medical University Hospital
Nagakute
Japan
+ 14 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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