Active, not recruitingNCT04544293IMPALA-2Updated Aug 26, 2026Results posted

Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)

A Phase 3 interventional study of Molgramostim and Placebo in Autoimmune Pulmonary Alveolar Proteinosis, sponsored by Savara Inc.. Active, not recruiting at 54 sites in 18 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-26.

Sponsored by Savara Inc. · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 164
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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. 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.

Conditions studied

Autoimmune Pulmonary Alveolar Proteinosis

Keywords

aPAP

In context

Lead sponsor

Savara Inc. is the lead sponsor of 11 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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).
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.
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.
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.

Exclusion criteria

Exclusion Criteria:

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.
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.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 164 participants (actual)

Study arms

Experimental
Molgramostim
Double-blind treatment with molgramostim nebulizer solution 300 µg once daily (Mol OD) for 48 weeks
Drug: Molgramostim
Placebo comparator
Placebo
Double-blind treatment with placebo (PBO) nebulizer solution once daily for 48 weeks
Drug: Placebo
Experimental
Molgramostim Open-label Extension
Open-label treatment with molgramostim nebulizer solution 300 µg once daily (Mol OD) for 96 weeks
Drug: Molgramostim Open-label

Interventions

DrugMolgramostim
Molgramostim 300 µg nebulizer solution
Also known as: Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF)
DrugPlacebo
Matching placebo nebulizer solution
Also known as: Placebo nebulizer
DrugMolgramostim Open-label
Molgramostim 300 µg nebulizer solution
Also known as: Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF)

What researchers measure

Primary outcomes

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).
Time frame: From Baseline to Week 24

Secondary outcomes

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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: From Baseline to Week 24
Number of Subjects With Serious and Non-serious Adverse Events
Assessment of the safety of molgramostim compared to placebo
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
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).
Time frame: 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.
Time frame: 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.
Time frame: From Baseline to Weeks 24 and 48
Change in QT Interval Corrected by Fridericia (QTcF)
Assessment of the safety of MOL compared to placebo
Time frame: From Baseline to Weeks 4 and 24

Results

Posted Aug 7, 2025

Participant flow

Outpatient Medical Clinics 19 May 2021 -16 June 2023

Double-blind

Participant flow — Double-blind
Milestone	Molgramostim	Placebo
Started	81	83
Completed	79	80
Not completed	2	3
Withdrew: Adverse event	2	1
Withdrew: Pregnancy	0	1
Withdrew: Lost to follow-up	0	1

Open-Label Extension

Participant flow — Open-Label Extension
Milestone	Molgramostim	Placebo
Started	79	81
Completed	0	0
Not completed	79	81
Withdrew: Study ongoing	79	81

Outcome measures

PrimaryChange 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).

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · % predicted DLCO adjusted for hemoglobin

Change From Baseline in Percent (%) Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted for Hemoglobin Concentration to Week 24
% predicted DLCO adjusted for hemoglobin	Molgramostim	Placebo
Change From Baseline in Percent (%) Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted for Hemoglobin Concentration to Week 24	9.8 (7.3 to 12.3)	3.8 (1.4 to 6.3)

Statistical analysis

Molgramostim vs Placebo · Mixed Models Analysis · p = 0.0007 · Mean difference (net): 6.0 · 95% CI 2.5 to 9.4Difference from placebo

SecondaryChange From Baseline in Percent (%) Predicted DLCO Adjusted for Hemoglobin Concentration (%DLCOadj) to Week 48

Time frame:: From Baseline to Week 48
Reported as:: Least squares mean · Unit of Measure: % predicted DLCO adjust

Change From Baseline in Percent (%) Predicted DLCO Adjusted for Hemoglobin Concentration (%DLCOadj) to Week 48
Unit of Measure: % predicted DLCO adjust	Molgramostim	Placebo
Change From Baseline in Percent (%) Predicted DLCO Adjusted for Hemoglobin Concentration (%DLCOadj) to Week 48	11.6 (8.7 to 14.5)	4.7 (1.8 to 7.6)

Statistical analysis

Molgramostim vs Placebo · Mixed Models Analysis · p = 0.0008 (Modelled using MMRM adjusted for baseline % predicted DLCOadj, treatment, visit, region, severity stratification and treatment-visit interaction.) · Mean difference (net): 6.9 · 95% CI 2.9 to 10.9Difference from Placebo

SecondaryChange 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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · Change from baseline units on a scale

Change From Baseline in St. Georges Respiratory Questionnaire (SGRQ) Total Score to Week 24
Change from baseline units on a scale	Molgramostim	Placebo
Change From Baseline in St. Georges Respiratory Questionnaire (SGRQ) Total Score to Week 24	-11.5 (-15.01 to -7.98)	-4.9 (-8.28 to -1.52)

Statistical analysis

Molgramostim vs Placebo · Mixed Models Analysis · p = 0.0072 · Mean difference (net): -6.59 · 95% CI -11.40 to -1.79

SecondaryChange 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

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · units on a scale

Change From Baseline in SGRQ Activity Component Score to Week 24
units on a scale	Molgramostim	Placebo
Change From Baseline in SGRQ Activity Component Score to Week 24	-13.03 (-17.58 to -8.49)	-5.22 (-9.76 to -0.69)

Statistical analysis

Molgramostim vs Placebo · Mixed Models Analysis · p = 0.0149 · Mean difference (net): -7.81 · 95% CI -14.10 to -1.52

SecondaryChange 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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · Change from baseline in METS

Change From Baseline in Exercise Capacity (EC), Expressed as Peak Metabolic Equivalents (METs) to Week 24
Change from baseline in METS	Molgramostim	Placebo
Change From Baseline in Exercise Capacity (EC), Expressed as Peak Metabolic Equivalents (METs) to Week 24	1.11 (0.76 to 1.46)	0.70 (0.34 to 1.05)

Statistical analysis

Molgramostim vs Placebo · Mixed Models Analysis · p = 0.0845 · Mean difference (final values): 0.41 · 95% CI -0.06 to 0.89

SecondaryChange From Baseline in SGRQ Total Score to Week 48

Time frame:: From Baseline to Week 48
Reported as:: Least squares mean · Change from baseline units on a scale

Change From Baseline in SGRQ Total Score to Week 48
Change from baseline units on a scale	Molgramostim	Placebo
Change From Baseline in SGRQ Total Score to Week 48	-10.72 (-15.01 to -6.44)	-5.85 (-9.96 to -1.74)

Statistical analysis

Molgramostim vs Placebo · Mixed Models Analysis · p = 0.1046 · Mean difference (net): -4.87 · 95% CI -10.76 to 1.01

SecondaryChange From Baseline in SGRQ Activity From Baseline to Week 48

Time frame:: From Baseline to Week 48
Reported as:: Least squares mean · Change from baseline score on a scale

Change From Baseline in SGRQ Activity From Baseline to Week 48
Change from baseline score on a scale	Molgramostim	Placebo
Change From Baseline in SGRQ Activity From Baseline to Week 48	-13.39 (-18.87 to -7.91)	-7.40 (-12.72 to -2.09)

Statistical analysis

Molgramostim vs Placebo · Mixed Models Analysis · p = 0.1216 · Mean difference (net): -5.99 · 95% CI -13.57 to 1.59

SecondaryChange From Baseline in EC, Expressed as Peak METs to Week 48

Time frame:: From Baseline to Week 48
Reported as:: Least squares mean · Change from baseline in METS

Change From Baseline in EC, Expressed as Peak METs to Week 48
Change from baseline in METS	Molgramostim	Placebo
Change From Baseline in EC, Expressed as Peak METs to Week 48	1.13 (0.77 to 1.49)	0.58 (0.22 to 0.93)

Statistical analysis

Molgramostim vs Placebo · Mixed Models Analysis · p = 0.0234 · Mean difference (final values): 0.55 · 95% CI 0.07 to 1.03Change from baseline compared to placebo.

SecondaryChange 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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · mmHg

Change From Baseline in Alveolar-arterial Oxygen Difference (A-aDO2) to Week 24 (All Subjects)
mmHg	Molgramostim	Placebo
Change From Baseline in Alveolar-arterial Oxygen Difference (A-aDO2) to Week 24 (All Subjects)	-7.97 (-11.62 to -4.32)	-3.96 (-7.48 to -0.44)

Statistical analysis

Molgramostim vs Placebo · Mixed Models Analysis · p = 0.1043 · Mean difference (final values): -4.01 · 95% CI -8.84 to 0.83

SecondaryNumber of Subjects With Serious and Non-serious Adverse Events

Assessment of the safety of molgramostim compared to placebo

Time frame:: From Baseline until End of Double-blind treatment (Week 48)
Reported as:: Number · participants

Number of Subjects With Serious and Non-serious Adverse Events
participants	Molgramostim	Placebo
Any TEAE	69	71
Any TESAE	14	20

SecondaryNumber 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).

Time frame:: From Baseline until End of Double-blind treatment Week-48
Reported as:: Count of participants · Participants

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
Participants	Molgramostim	Placebo
Week 24	28	30
Week 48	39	37

SecondaryChanges 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.

Time frame:: From Baseline to Weeks 24 and 48
Reported as:: Mean · % FVC predicted

Changes in Forced Vital Capacity (FVC) %Predicted Normal
% FVC predicted	Molgramostim	Placebo
Week 24	3.2 ± 6.20	0.9 ± 5.74
Week 48	3.2 ± 7.92	-0.1 ± 8.27

SecondaryChanges 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.

Time frame:: From Baseline to Weeks 24 and 48
Reported as:: Mean · %predicted normal

Changes in Forced Expiratory Volume in One Second (FEV1) % Predicted Normal.
%predicted normal	Molgramostim	Placebo
Week 24	1.2 ± 7.08	-0.3 ± 5.35
Week 48	1.4 ± 7.98	-1.4 ± 7.56

SecondaryChange in QT Interval Corrected by Fridericia (QTcF)

Assessment of the safety of MOL compared to placebo

Time frame:: From Baseline to Weeks 4 and 24
Reported as:: Mean · msec

Change in QT Interval Corrected by Fridericia (QTcF)
msec	Molgramostim	Placebo
Week 4	-2.51 ± 10.543	1.59 ± 10.127
Week 24	-1.89 ± 13.190	-0.96 ± 11.534

Adverse events

Collected over Adverse events during double-blind treatment (48 Weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Molgramostim	0/81 (0%)	14/81 (17.3%)	69/81 (85.2%)
Placebo	0/83 (0%)	20/83 (24.1%)	71/83 (85.5%)

Most frequent serious events

Showing 10 of 24

Most frequent serious events
Event	Molgramostim	Placebo
Alveolar proteinosisRespiratory, thoracic and mediastinal disorders	3/81	9/83
HypoxiaRespiratory, thoracic and mediastinal disorders	1/81	3/83
DyspnoeaRespiratory, thoracic and mediastinal disorders	2/81	1/83
COVID-19Infections and infestations	2/81	0/83
PneumoniaRespiratory, thoracic and mediastinal disorders	1/81	1/83
Mycobacterium avium complex infectionInfections and infestations	1/81	0/83
Sudden hearing lossEar and labyrinth disorders	1/81	0/83
Clavicle fractureInjury, poisoning and procedural complications	1/81	0/83
DelusionPsychiatric disorders	1/81	0/83
Uterine polypReproductive system and breast disorders	1/81	0/83

Most frequent other events

Showing 10 of 21

Most frequent other events
Event	Molgramostim	Placebo
CoughRespiratory, thoracic and mediastinal disorders	17/81	18/83
Covid-19Infections and infestations	16/81	8/83
NasopharyngitisInfections and infestations	11/81	7/83
PyrexiaGeneral disorders	11/81	9/83
ArthralgiaMusculoskeletal and connective tissue disorders	9/81	7/83
DiarrheaGastrointestinal disorders	9/81	2/83
HeadacheNervous system disorders	9/81	7/83
Back painMusculoskeletal and connective tissue disorders	7/81	3/83
DizzinessNervous system disorders	7/81	2/83
Non-cardiac chest painGeneral disorders	7/81	5/83

Baseline characteristics

One subject in the placebo group stopped randomized drug but continued in the study to complete all visits and assessments

Age, Continuous
Age, Continuous(years)	Molgramostim	Placebo	Total
Mean	50.8 ± 13.03	48.4 ± 12.69	49.6 ± 12.87

Sex: Female, Male
Sex: Female, Male(Participants)	Molgramostim	Placebo	Total
Female	37	29	66
Male	44	54	98

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Molgramostim	Placebo	Total
American Indian or Alaska Native	0	0	0
Asian	36	37	73
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	3	2	5
White	38	40	78
More than one race	0	0	0
Unknown or Not Reported	4	4	8

Region of Enrollment
Region of Enrollment(participants)	Molgramostim	Placebo	Total
Romania	4	2	6
United States	11	12	23
Japan	29	24	53
United Kingdom	1	2	3
Portugal	0	1	1
Spain	2	0	2
Canada	5	2	7
South Korea	6	10	16
Turkey	8	10	18
Belgium	0	1	1
Ireland	2	0	2
Poland	0	3	3
Italy	4	5	9
Australia	0	1	1
France	5	4	9
Germany	4	6	10

%DLCOadj at Baseline
%DLCOadj at Baseline(%)	Molgramostim	Placebo	Total
Median	54.0 (25 to 72)	55.0 (28 to 71)	55 (25 to 72)

%DLCOadj at Randomization <=50%
%DLCOadj at Randomization <=50%(Participants)	Molgramostim	Placebo	Total
Count of participants	31	32	63

%DLCOadj at Randomization >50%
%DLCOadj at Randomization >50%(Participants)	Molgramostim	Placebo	Total
Count of participants	50	51	101

Study locations

54 sites

University Of Arkansas For Medical Services
Little Rock, Arkansas 72205, United States
UCLA David Geffen School of Medicine
Los Angeles, California 90095, United States
National Jewish Health
Denver, Colorado 80206, United States
Yale University
New Haven, Connecticut 06520, United States
University of Florida Health
Gainesville, Florida 32610, United States
Emory University
Atlanta, Georgia 30322, United States
Loyola University
Maywood, Illinois 60153, United States
University of Maryland Medical Center
Baltimore, Maryland 21201, United States
Washington University in St. Louis
St Louis, Missouri 63110, United States
Duke University Medical Center
Durham, North Carolina 27710, United States
Wake Med Health & Hospital
Raleigh, North Carolina 27610, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229-3039, United States
Cleveland Clinic
Cleveland, Ohio 44195, United States
University of Pennsylvania Perelman School of Medicine - Pulmonology
Philadelphia, Pennsylvania 19104, United States
University of Pittsburgh
Pittsburgh, Pennsylvania 15213, United States
UT Southwestern Medical Center
Dallas, Texas 75390, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales 2050, Australia
Westmead Hospital
Westmead, New South Wales 2145, Australia
Hôpital Erasme
Brussels, Brussels Capital 1070, Belgium
UZ Leuven - Campus Gasthuisberg - Pneumologie
Leuven, Vlaams Brabant 3000, Belgium
University of Calgary
Calgary, Alberta T2N 4N1, Canada
St Joseph's Healthcare Hamilton Research
Hamilton, Ontario L8N 4A6, Canada
University Institute of Cardiology and Respirology of Quebec
Québec, Quebec G1V 4G5, Canada
Hôpital Louis Pradel
Bron, Auvergne-Rhône-Alpes 69500, France
CHU Pontchaillou
Rennes, Brittany Region 35033, France
Thoraxklinik Heidelberg gGmbH am Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg 69126, Germany
Asklepios Fachkliniken Muenchen-Gauting
Muenchen-Gauting, Bavaria 82131, Germany
Ruhrlandklinik Westdeutsches Lungenzentrum
Essen, North Rhine-Westphalia 45239, Germany
Attikon University Hospital
Athens, 12462, Greece
St. Vincent's University Hospital
Dublin, DO4 T6F4, Ireland
Fondazione IRCCS Policlinico San Matteo
Pavia, Lombardy 27100, Italy
Chiba University Hospital - Respiratory Medicine
Chiba, Chiba 260-8677, Japan
Hokkaido University Hospital
Sapporo, Hokkaidô 060-8648, Japan
Kanagawa Cardiovascular and Respiratory Center
Yokohama, Kanagawa 236-0051, Japan
Kumamoto University Hospital
Kumamoto, Kumamoto 860-8556, Japan
Tohoku University Hospital - Respiratory Tract Medicine
Sendai, Miyagi 980-8574, Japan
National Hospital Organization Kinki-Chuo Chest medical Center
Sakai, Osaka 591-8555, Japan
Saitama Red Cross Hospital
Saitama, Saitama 330-8553, Japan
Kyorin University Hospital
Mitaka, Tokyo 181-8611, Japan
Aichi Medical University Hospital
Nagakute, 480-1195, Japan
St Antonius Hospital
Nieuwegein, Utrecht 3435CM, Netherlands
Instytut Gruzlicy i Chorob Pluc
Warsaw, Masovian Voivodeship 01-138, Poland
Hospital Pulido Valente
Lisbon, Lisbon District 1769-001, Portugal
Hospital São João
Porto, Porto District 4200-319, Portugal
Institutul de Pneumoftiziologie "Marius Nasta"
Bucharest, Bucharest 050159, Romania
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital - Yonsei University Health System - Pulmonary
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Hospital Universitario de Bellvitge
Barcelona, Catalonia 08907, Spain
Health Sciences University Gulhane Training and Research Hospital
Ankara, Ankara 6010, Turkey (Türkiye)
Yedikule Chest Disease and Surgery Training and Research Hospital
Istanbul, Istanbul 34020, Turkey (Türkiye)
Ege University Hospital - Department of Pulmonology
Bornova, İzmir 35100, Turkey (Türkiye)
Royal Brompton and Harefield NHS Foundation Trust
London, London SW3 6NP, United Kingdom

References and documents

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 documents

Study protocol · Oct 9, 2024
Statistical analysis plan · Apr 24, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 26, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04544293
Lead sponsor: Savara Inc.
Responsible party: Sponsor
First posted: Sep 10, 2020
Start date: May 19, 2021
Primary completion: Nov 30, 2023
Completion: May 30, 2027 (estimated)
Results posted: Aug 7, 2025
Last update: Aug 26, 2026

Study contacts

Bruce Trapnell, MD

principal investigator · Children's Hospital Medical Center, Cincinnati

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

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Study summary

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References and documents

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Follow this study

Discussion

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