Autoimmune Pulmonary Alveolar ProteinosisPhase 3IMPALA-2NCT04544293
Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
A Phase 3 study testing Molgramostim and Molgramostim Open-label in people with Autoimmune Pulmonary Alveolar Proteinosis, run by Savara Inc. at 54 sites in 18 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Pulmonary Alveolar Proteinosis
- What is being tested?
- Molgramostim and Molgramostim Open-label
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 164 participants
- Where
- 54 sitesin 18 countries
- Study dates
- 19 May 2021to 30 May 2027
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be ≥18 years of age, at the time of signing the informed consent (≥20 in Japan).
- A serum anti-GM-CSF autoantibody test result confirming autoimmune PAP.
- History of PAP, based on examination of a lung biopsy, bronchoalveolar lavage (BAL) cytology, or a high-resolution computed tomogram (HRCT) of the chest.
- A diffusing capacity for carbon monoxide of 70% predicted or lower adjusted for hemoglobin (%DLCOadj) at the screening and baseline visits.
- Change in %DLCO adj of <15% points during the screening period.
- Demonstrated functional impairment in the treadmill exercise test (defined as a peak metabolic equivalent (MET) ≤8).
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- 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.
- Resting oxygen saturation (SpO2) >85% during 15 minutes without use of supplemental oxygen at the screening visits.
- Male or female
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- 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.
- 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.
- 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.
- 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.
Who cannot join
- Diagnosis of hereditary or secondary PAP, or a metabolic disorder of surfactant production.
- Whole lung lavage (WLL) performed within 3 months prior to baseline.
- Requirement for WLL at screening or baseline.
- GM-CSF treatment within 6 months prior to baseline.
- Treatment with rituximab within 6 months prior to baseline.
- Treatment with plasmapheresis within 6 weeks prior to baseline.
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- Treatment with any investigational medicinal product within 5 half-lives or 3 months (whichever is longer) prior to baseline.
- Previously randomized in this trial.
- History of allergic reactions to GM-CSF or any of the excipients in the nebulizer solution.
- Inflammatory or autoimmune disease of a severity that necessitates significant (e.g. more than 10 mg/day systemic prednisolone) immunosuppression.
- Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product.
- History of, or present, myeloproliferative disease or leukemia.
- Apparent pre-existing concurrent pulmonary fibrosis.
- Acute or unstable cardiac or pulmonary disease that may be aggravated by exercise.
- Known active infection (viral, bacterial, fungal, or mycobacterial) that may affect the efficacy evaluation in the trial.
- Physical disability or other condition that precludes safe and adequate exercise testing.
- Any other serious medical condition which in the opinion of the Investigator would make the subject unsuitable for the trial.
- 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.
- 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.
Trial locations and contacts
54 sites in 18 countries.
54 sites in 18 countries
United States16 sites
Emory University
Atlanta, Georgia, 30322
University of Maryland Medical Center
Baltimore, Maryland, 21201
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Cleveland Clinic
Cleveland, Ohio, 44195
UT Southwestern Medical Center
Dallas, Texas, 75390
National Jewish Health
Denver, Colorado, 80206
Duke University Medical Center
Durham, North Carolina, 27710
University of Florida Health
Gainesville, Florida, 32610
University Of Arkansas For Medical Services
Little Rock, Arkansas, 72205
UCLA David Geffen School of Medicine
Los Angeles, California, 90095
Loyola University
Maywood, Illinois, 60153
Yale University
New Haven, Connecticut, 06520
University of Pennsylvania Perelman School of Medicine - Pulmonology
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Wake Med Health & Hospital
Raleigh, North Carolina, 27610
Washington University in St. Louis
St Louis, Missouri, 63110
Japan9 sites
Chiba University Hospital - Respiratory Medicine
Chiba, Chiba, 260-8677
Kumamoto University Hospital
Kumamoto, Kumamoto, 860-8556
Kyorin University Hospital
Mitaka, Tokyo, 181-8611
Aichi Medical University Hospital
Nagakute, 480-1195
Saitama Red Cross Hospital
Saitama, Saitama, 330-8553
National Hospital Organization Kinki-Chuo Chest medical Center
Sakai, Osaka, 591-8555
Hokkaido University Hospital
Sapporo, Hokkaidô, 060-8648
Tohoku University Hospital - Respiratory Tract Medicine
Sendai, Miyagi, 980-8574
Kanagawa Cardiovascular and Respiratory Center
Yokohama, Kanagawa, 236-0051
South Korea4 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital - Yonsei University Health System - Pulmonary
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Canada3 sites
University of Calgary
Calgary, Alberta, T2N 4N1
St Joseph's Healthcare Hamilton Research
Hamilton, Ontario, L8N 4A6
University Institute of Cardiology and Respirology of Quebec
Québec, Quebec, G1V 4G5
Germany3 sites
Ruhrlandklinik Westdeutsches Lungenzentrum
Essen, North Rhine-Westphalia, 45239
Thoraxklinik Heidelberg gGmbH am Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69126
Asklepios Fachkliniken Muenchen-Gauting
Muenchen-Gauting, Bavaria, 82131
Turkey (Türkiye)3 sites
Health Sciences University Gulhane Training and Research Hospital
Ankara, Ankara, 6010
Ege University Hospital - Department of Pulmonology
Bornova, İzmir, 35100
Yedikule Chest Disease and Surgery Training and Research Hospital
Istanbul, Istanbul, 34020
Australia2 sites
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Westmead Hospital
Westmead, New South Wales, 2145
Belgium2 sites
Hôpital Erasme
Brussels, Brussels Capital, 1070
UZ Leuven - Campus Gasthuisberg - Pneumologie
Leuven, Vlaams Brabant, 3000
France2 sites
Hôpital Louis Pradel
Bron, Auvergne-Rhône-Alpes, 69500
CHU Pontchaillou
Rennes, Brittany Region, 35033
Portugal2 sites
Hospital Pulido Valente
Lisbon, Lisbon District, 1769-001
Hospital São João
Porto, Porto District, 4200-319
Poland1 site
Instytut Gruzlicy i Chorob Pluc
Warsaw, Masovian Voivodeship, 01-138
Romania1 site
Institutul de Pneumoftiziologie "Marius Nasta"
Bucharest, Bucharest, 050159
United Kingdom1 site
Royal Brompton and Harefield NHS Foundation Trust
London, London, SW3 6NP
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Clinical Trial of Once-daily Inhaled Molgramostim Nebulizer Solution in Adult Subjects With Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
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.
Read the detailed description
This is an interventional, randomized, double-blind, 2-arm, parallel groups, placebo-controlled, multi-center, phase 3 trial in adult subjects who are diagnosed with aPAP.
An aPAP diagnosis should be confirmed by a Granulocyte-macrophage colony stimulating factor (GM-CSF) auto-antibody test result, and history of PAP based on either high resolution computed tomography, lung biopsy, or bronchoalveolar lavage cytology, should be available.
The trial consists of a 6-week screening period, a 48-week randomized, double-blind treatment period, a 96-week open-label treatment period, and a conditional 4-week safety follow-up period. The maximum treatment duration will be 145 weeks and the maximum trial duration will be 156 weeks. During the trial, whole lung lavage will be allowed as rescue treatment in case of worsening of aPAP.
- Being tested
- Molgramostim, Placebo, Molgramostim Open-label
- Keywords
- aPAP
- Medical subject headings
- Pulmonary Alveolar Proteinosis, Acquired
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MolgramostimDrug
Also called Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF)
Molgramostim 300 µg nebulizer solution
PlaceboDrug
Also called Placebo nebulizer
Matching placebo nebulizer solution
Molgramostim Open-labelDrug
Also called Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF)
Molgramostim 300 µg nebulizer solution
| Study group | Role | What they receive |
|---|---|---|
| Molgramostim | Experimental | Double-blind treatment with molgramostim nebulizer solution 300 µg once daily (Mol OD) for 48 weeks Receives: Drug: Molgramostim |
| Placebo | Placebo comparator | Double-blind treatment with placebo (PBO) nebulizer solution once daily for 48 weeks Receives: Drug: Placebo |
| Molgramostim Open-label Extension | Experimental | Open-label treatment with molgramostim nebulizer solution 300 µg once daily (Mol OD) for 96 weeks Receives: Drug: Molgramostim Open-label |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Percent (%) Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted for Hemoglobin Concentration 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).
Measured: From Baseline to Week 24
Secondary outcomes (13)
Change From Baseline in Percent (%) Predicted DLCO Adjusted for Hemoglobin Concentration (%DLCOadj) to Week 48
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). Higher values indicate better respiratory gas exchange.
Measured: From Baseline to Week 48
Change From Baseline in St. Georges Respiratory Questionnaire (SGRQ) Total Score to Week 24
The Saint Georges Respiratory Questionnaire (SGRQ) is designed to measure respiratory health impairment. The scale includes questions related to three components: Activity (activities that cause or are limited by breathlessness), Impact (social functioning and psychological disturbances resulting from airway disease), and Symptoms (respiratory symptoms, their frequency and severity). The questionnaire has a recall period of 4 weeks for Symptoms, whereas Activity and Impact components address the subject's current state. SGRQ scored on a 0-100 scale with lower scores indicating better respiratory health.
Measured: From Baseline to Week 24
Change From Baseline in SGRQ Activity Component Score to Week 24
The Saint Georges Respiratory Questionnaire (SGRQ) Activity scale is a subscale of the SGRQ and is designed to measure the effect of respiratory health impairment on daily activity affected by breathlessness. The questionnaire for the Activity components addresses the subject's current state. SGRQ Activity is scored on a 0-100 scale with lower scores indicating better respiratory health activity
Measured: From Baseline to Week 24
Change From Baseline in Exercise Capacity (EC), Expressed as Peak Metabolic Equivalents (METs) to Week 24
As a functional measure of exertional limitations related to dyspnea, EC was assessed by an exercise treadmill test. EC was expressed in peak METs (1 MET=3.5 mL O2/kg/min). The highest treadmill speed and grade achieved was used to calculate peak METs. Higher values indicate better functional capacity.
Measured: From Baseline to Week 24
Change From Baseline in SGRQ Total Score to Week 48
The Saint Georges Respiratory Questionnaire (SGRQ) is designed to measure respiratory health impairment. The scale includes questions related to three components: Activity (activities that cause or are limited by breathlessness), Impact (social functioning and psychological disturbances resulting from airway disease), and Symptoms (respiratory symptoms, their frequency and severity). The questionnaire has a recall period of 4 weeks for Symptoms, whereas Activity and Impact components address the subject's current state. SGRQ scored on a 0-100 scale with lower scores indicating better respiratory health.
Measured: From Baseline to Week 48
Change From Baseline in SGRQ Activity From Baseline to Week 48
The Saint Georges Respiratory Questionnaire (SGRQ) Activity scale is a subscale of the SGRQ and is designed to measure the effect of respiratory health impairment on daily activity affected by breathlessness. The questionnaire for the Activity components addresses the subject's current state. SGRQ Activity is scored on a 0-100 scale with lower scores indicating better respiratory health activity
Measured: From Baseline to Week 48
Change From Baseline in EC, Expressed as Peak METs to Week 48
As a functional measure of exertional limitations related to dyspnea, EC was assessed by an exercise treadmill test. EC was expressed in peak METs (1 MET=3.5 mL O2/kg/min). The highest treadmill speed and grade achieved was used to calculate peak METs. Higher values indicate better functional capacity.
Measured: From Baseline to Week 48
Change From Baseline in Alveolar-arterial Oxygen Difference (A-aDO2) to Week 24 (All Subjects)
A-aDO2 was used as an additional measure of gas exchange.
Measured: From Baseline to Week 24
Number of Subjects With Serious and Non-serious Adverse Events
Assessment of the safety of molgramostim compared to placebo
Measured: From Baseline until End of Double-blind treatment (Week 48)
Number of Subjects With Positive Treatment-boosted Anti Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Antibody Titers During 24 Weeks' Treatment and During 48 Weeks' Treatment
Assess the effect of molgramostim or placebo on antiGM-CSF antibody titers that increased by a dilution factor of 2.(4X increase in titer compared to Baseline).
Measured: From Baseline until End of Double-blind treatment Week-48
Changes in Forced Vital Capacity (FVC) %Predicted Normal
Forced vital capacity is the volume of air that can be expired after a deep breath. Higher volumes indicate better respiratory function. FVC is scored as % of predicted normal expired vital capacity.
Measured: From Baseline to Weeks 24 and 48
Changes in Forced Expiratory Volume in One Second (FEV1) % Predicted Normal.
FEV1 is the volume of air expired in 1 second in liters (L). Higher values indicate better respiratory function.
Measured: From Baseline to Weeks 24 and 48
Change in QT Interval Corrected by Fridericia (QTcF)
Assessment of the safety of MOL compared to placebo
Measured: From Baseline to Weeks 4 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2020
- Study start19 May 2021
- Primary completion30 Nov 2023
- Study completion30 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autoimmune Pulmonary Alveolar ProteinosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subject will be randomized 1:1 to treatment with inhaled molgramostim or placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Savara Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bruce Trapnell, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04544293
- Sponsor's protocol ID
- SAV006-05
- Other IDs
- 2020-001263-85
- Acronym
- IMPALA-2
- Status last verified
- Oct 2026
- First submitted
- 3 Sep 2020
- Last updated
- 3 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Trapnell BC, Inoue Y, Bonella F, Wang T, McCarthy C, Arai T, Akasaka K, Mariani F, Mogulkoc N, Song JW, Baba T, Jouneau S, Numakura T, Ocal N, Mihaltan F, Ataya A, Bendstrup E, Campo I, Carey B, Arena R, Robinson B, Fleming R, Wasfi Y, Pratt R; IMPALA-2 Trial Investigators. Phase 3 Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis. N Engl J Med. 2025 Aug 21;393(8):764-773. doi: 10.1056/NEJMoa2410542.
PubMed 40834301
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Clinical Trial of Once-daily Inhaled Molgramostim Nebulizer Solution in Adult Subjects With Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
- ClinicalTrials.gov ID
- NCT04544293
- Acronym / sponsor ID
- IMPALA-2 / SAV006-05
- Keywords
- aPAP
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Savara Inc.Industry (pharma, biotech, devices)
- Study start
- 19 May 2021 (actual)
- Primary completion
- 30 Nov 2023 (actual)
- Study completion
- 30 May 2027 (estimated)
- First posted
- 10 Sep 2020 (actual)
- Results
- Posted 7 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an interventional, randomized, double-blind, 2-arm, parallel groups, placebo-controlled, multi-center, phase 3 trial in adult subjects who are diagnosed with aPAP.
An aPAP diagnosis should be confirmed by a Granulocyte-macrophage colony stimulating factor (GM-CSF) auto-antibody test result, and history of PAP based on either high resolution computed tomography, lung biopsy, or bronchoalveolar lavage cytology, should be available.
The trial consists of a 6-week screening period, a 48-week randomized, double-blind treatment period, a 96-week open-label treatment period, and a conditional 4-week safety follow-up period. The maximum treatment duration will be 145 weeks and the maximum trial duration will be 156 weeks. During the trial, whole lung lavage will be allowed as rescue treatment in case of worsening of aPAP.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Subject will be randomized 1:1 to treatment with inhaled molgramostim or placebo
| Arm | Type | Receives |
|---|---|---|
| Molgramostim | Experimental | Drug: MolgramostimDouble-blind treatment with molgramostim nebulizer solution 300 µg once daily (Mol OD) for 48 weeks |
| Placebo | Placebo comparator | Drug: PlaceboDouble-blind treatment with placebo (PBO) nebulizer solution once daily for 48 weeks |
| Molgramostim Open-label Extension | Experimental | Drug: Molgramostim Open-labelOpen-label treatment with molgramostim nebulizer solution 300 µg once daily (Mol OD) for 96 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Subject must be ≥18 years of age, at the time of signing the informed consent (≥20 in Japan).
- A serum anti-GM-CSF autoantibody test result confirming autoimmune PAP.
- History of PAP, based on examination of a lung biopsy, bronchoalveolar lavage (BAL) cytology, or a high-resolution computed tomogram (HRCT) of the chest.
- A diffusing capacity for carbon monoxide of 70% predicted or lower adjusted for hemoglobin (%DLCOadj) at the screening and baseline visits.
- Change in %DLCO adj of <15% points during the screening period.
Key exclusion criteria (19 listed)
- Diagnosis of hereditary or secondary PAP, or a metabolic disorder of surfactant production.
- Whole lung lavage (WLL) performed within 3 months prior to baseline.
- Requirement for WLL at screening or baseline.
- GM-CSF treatment within 6 months prior to baseline.
- Treatment with rituximab within 6 months prior to baseline.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MolgramostimAlso: Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF)Molgramostim 300 µg nebulizer solution | Drug | Molgramostim |
| PlaceboAlso: Placebo nebulizerMatching placebo nebulizer solution | Drug | Placebo |
| Molgramostim Open-labelAlso: Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF)Molgramostim 300 µg nebulizer solution | Drug | Molgramostim Open-label Extension |
Primary outcome
Change From Baseline in Percent (%) Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted for Hemoglobin Concentration to Week 24
Time frame: 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).
13 secondary outcomes
Change From Baseline in Percent (%) Predicted DLCO Adjusted for Hemoglobin Concentration (%DLCOadj) to Week 48
Time frame: From Baseline to Week 48
Change From Baseline in St. Georges Respiratory Questionnaire (SGRQ) Total Score to Week 24
Time frame: From Baseline to Week 24
Change From Baseline in SGRQ Activity Component Score to Week 24
Time frame: From Baseline to Week 24
Change From Baseline in Exercise Capacity (EC), Expressed as Peak Metabolic Equivalents (METs) to Week 24
Time frame: From Baseline to Week 24
Change From Baseline in SGRQ Total Score to Week 48
Time frame: From Baseline to Week 48
Change From Baseline in SGRQ Activity From Baseline to Week 48
Time frame: From Baseline to Week 48
Change From Baseline in EC, Expressed as Peak METs to Week 48
Time frame: From Baseline to Week 48
Change From Baseline in Alveolar-arterial Oxygen Difference (A-aDO2) to Week 24 (All Subjects)
Time frame: From Baseline to Week 24
Number of Subjects With Serious and Non-serious Adverse Events
Time frame: From Baseline until End of Double-blind treatment (Week 48)
Number of Subjects With Positive Treatment-boosted Anti Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Antibody Titers During 24 Weeks' Treatment and During 48 Weeks' Treatment
Time frame: From Baseline until End of Double-blind treatment Week-48
Changes in Forced Vital Capacity (FVC) %Predicted Normal
Time frame: From Baseline to Weeks 24 and 48
Changes in Forced Expiratory Volume in One Second (FEV1) % Predicted Normal.
Time frame: From Baseline to Weeks 24 and 48
Change in QT Interval Corrected by Fridericia (QTcF)
Time frame: From Baseline to Weeks 4 and 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40834301Trapnell BC, Inoue Y, Bonella F, Wang T, McCarthy C, Arai T, Akasaka K, Mariani F, Mogulkoc N, Song JW, Baba T, Jouneau S, Numakura T, Ocal N, Mihaltan F, Ataya A, Bendstrup E, Campo I, Carey B, Arena R, Robinson B, Fleming R, Wasfi Y, Pratt R; IMPALA-2 Trial Investigators. Phase 3 Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis. N Engl J Med. 2025 Aug 21;393(8):764-773. doi: 10.1056/NEJMoa2410542.
- Individual participant dataSharing planned: No
Related trials for Autoimmune Pulmonary Alveolar Proteinosis
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Not yet recruitingPhase 2
Local Spraying of GM-CSF Via Bronchoscopy in the Treatment of Autoimmune Pulmonary Alveolar Proteinosis
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce Trapnell, MD principal investigator
Children's Hospital Medical Center, Cincinnati
54 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Molgramostim and Molgramostim Open-label in people with Autoimmune Pulmonary Alveolar Proteinosis, run by Savara Inc. at 54 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 54 sites in United States, Japan, South Korea, Canada, Germany and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Percent (%) Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted for Hemoglobin Concentration to Week 24 (time frame: From Baseline to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04544293, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.