Autoimmune Pulmonary Alveolar Proteinosis
Conditions
Keywords
aPAP
Brief 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.
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.
Interventions
DRUGMolgramostim
Molgramostim 300 µg nebulizer solution
DRUGPlacebo
Matching placebo nebulizer solution
DRUGMolgramostim Open-label
Molgramostim 300 µg nebulizer solution
Sponsors
Savara Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Subject will be randomized 1:1 to treatment with inhaled molgramostim or placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in St. Georges Respiratory Questionnaire (SGRQ) Total Score to Week 24 | From Baseline 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. |
| Change From Baseline in SGRQ Activity Component Score to Week 24 | From Baseline 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 |
| Change From Baseline in Exercise Capacity (EC), Expressed as Peak Metabolic Equivalents (METs) to Week 24 | From Baseline 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. |
| Change From Baseline in SGRQ Total Score to Week 48 | From Baseline 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. |
| Change From Baseline in SGRQ Activity From Baseline to Week 48 | 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 |
| Change From Baseline in EC, Expressed as Peak METs to Week 48 | From Baseline 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. |
| Change From Baseline in Percent (%) Predicted DLCO Adjusted for Hemoglobin Concentration (%DLCOadj) to Week 48 | From Baseline 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. |
| Number of Subjects With Serious and Non-serious Adverse Events | From Baseline until End of Double-blind treatment (Week 48) | Assessment of the safety of molgramostim compared to placebo |
| 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 | From Baseline until End of Double-blind treatment Week-48 | 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). |
| Changes in Forced Vital Capacity (FVC) %Predicted Normal | From Baseline to Weeks 24 and 48 | 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. |
| Changes in Forced Expiratory Volume in One Second (FEV1) % Predicted Normal. | From Baseline to Weeks 24 and 48 | FEV1 is the volume of air expired in 1 second in liters (L). Higher values indicate better respiratory function. |
| Change in QT Interval Corrected by Fridericia (QTcF) | From Baseline to Weeks 4 and 24 | Assessment of the safety of MOL compared to placebo |
| Change From Baseline in Alveolar-arterial Oxygen Difference (A-aDO2) to Week 24 (All Subjects) | From Baseline to Week 24 | A-aDO2 was used as an additional measure of gas exchange. |
Countries
Australia, Belgium, Canada, France, Germany, Greece, Ireland, Italy, Japan, Netherlands, Poland, Portugal, Romania, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Outpatient Medical Clinics 19 May 2021 -16 June 2023
Pre-assignment details
Two screening visits were conducted 6 and 3 weeks prior to the Day 1 baseline visit. At the baseline visit, eligible subjects were centrally randomized through a Randomization and Trial Supply Management system to 48 weeks of double-blind treatment with MOL-OD or PBO. To be randomized patients were required to have a percent predicted DLCO adjusted for hemoglobin (%DLCOadj) of 70% or less and no variation in %DLCOadj of +/-15%.
Participants by arm
| Arm | Count |
|---|---|
| Molgramostim Double-blind treatment with molgramostim nebulizer solution 300 µg once daily for 48 weeks
Molgramostim: Molgramostim 300 µg nebulizer solution | 81 |
| Placebo Double-blind treatment with placebo nebulizer solution once daily for 48 weeks
Placebo: Matching placebo nebulizer solution | 83 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind | Adverse Event | 2 | 1 |
| Double-blind | Lost to Follow-up | 0 | 1 |
| Double-blind | Pregnancy | 0 | 1 |
| Open-Label Extension | Study ongoing | 79 | 81 |
Baseline characteristics
| Characteristic | Total | Molgramostim | Placebo |
|---|---|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 12.87 | 50.8 years STANDARD_DEVIATION 13.03 | 48.4 years STANDARD_DEVIATION 12.69 |
| %DLCOadj at Baseline | 55 % | 54.0 % | 55.0 % |
| %DLCOadj at Randomization <=50% | 63 Participants | 31 Participants | 32 Participants |
| %DLCOadj at Randomization >50% | 101 Participants | 50 Participants | 51 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 73 Participants | 36 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) White | 78 Participants | 38 Participants | 40 Participants |
| Region of Enrollment Australia | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Belgium | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Canada | 7 participants | 5 participants | 2 participants |
| Region of Enrollment France | 9 participants | 5 participants | 4 participants |
| Region of Enrollment Germany | 10 participants | 4 participants | 6 participants |
| Region of Enrollment Ireland | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Italy | 9 participants | 4 participants | 5 participants |
| Region of Enrollment Japan | 53 participants | 29 participants | 24 participants |
| Region of Enrollment Poland | 3 participants | 0 participants | 3 participants |
| Region of Enrollment Portugal | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Romania | 6 participants | 4 participants | 2 participants |
| Region of Enrollment South Korea | 16 participants | 6 participants | 10 participants |
| Region of Enrollment Spain | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Turkey | 18 participants | 8 participants | 10 participants |
| Region of Enrollment United Kingdom | 3 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 23 participants | 11 participants | 12 participants |
| Sex: Female, Male Female | 66 Participants | 37 Participants | 29 Participants |
| Sex: Female, Male Male | 98 Participants | 44 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 83 |
| other Total, other adverse events | 69 / 81 | 71 / 83 |
| serious Total, serious adverse events | 14 / 81 | 20 / 83 |
Outcome results
Primary
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
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Molgramostim | Change From Baseline in Percent (%) Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted for Hemoglobin Concentration to Week 24 | 9.8 % predicted DLCO adjusted for hemoglobin |
| Placebo | Change From Baseline in Percent (%) Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted for Hemoglobin Concentration to Week 24 | 3.8 % predicted DLCO adjusted for hemoglobin |
p-value: 0.000795% CI: [2.5, 9.4]Mixed Models Analysis
Secondary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Molgramostim | Change From Baseline in Alveolar-arterial Oxygen Difference (A-aDO2) to Week 24 (All Subjects) | -7.97 mmHg |
| Placebo | Change From Baseline in Alveolar-arterial Oxygen Difference (A-aDO2) to Week 24 (All Subjects) | -3.96 mmHg |
p-value: 0.104395% CI: [-8.84, 0.83]Mixed Models Analysis
Secondary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Molgramostim | Change From Baseline in EC, Expressed as Peak METs to Week 48 | 1.13 Change from baseline in METS |
| Placebo | Change From Baseline in EC, Expressed as Peak METs to Week 48 | 0.58 Change from baseline in METS |
p-value: 0.023495% CI: [0.07, 1.03]Mixed Models Analysis
Secondary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Molgramostim | Change From Baseline in Exercise Capacity (EC), Expressed as Peak Metabolic Equivalents (METs) to Week 24 | 1.11 Change from baseline in METS |
| Placebo | Change From Baseline in Exercise Capacity (EC), Expressed as Peak Metabolic Equivalents (METs) to Week 24 | 0.70 Change from baseline in METS |
p-value: 0.084595% CI: [-0.06, 0.89]Mixed Models Analysis
Secondary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Molgramostim | Change From Baseline in Percent (%) Predicted DLCO Adjusted for Hemoglobin Concentration (%DLCOadj) to Week 48 | 11.6 Unit of Measure: % predicted DLCO adjust |
| Placebo | Change From Baseline in Percent (%) Predicted DLCO Adjusted for Hemoglobin Concentration (%DLCOadj) to Week 48 | 4.7 Unit of Measure: % predicted DLCO adjust |
p-value: 0.000895% CI: [2.9, 10.9]Mixed Models Analysis
Secondary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Molgramostim | Change From Baseline in SGRQ Activity Component Score to Week 24 | -13.03 units on a scale |
| Placebo | Change From Baseline in SGRQ Activity Component Score to Week 24 | -5.22 units on a scale |
p-value: 0.014995% CI: [-14.1, -1.52]Mixed Models Analysis
Secondary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Molgramostim | Change From Baseline in SGRQ Activity From Baseline to Week 48 | -13.39 Change from baseline score on a scale |
| Placebo | Change From Baseline in SGRQ Activity From Baseline to Week 48 | -7.40 Change from baseline score on a scale |
p-value: 0.121695% CI: [-13.57, 1.59]Mixed Models Analysis
Secondary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Molgramostim | Change From Baseline in SGRQ Total Score to Week 48 | -10.72 Change from baseline units on a scale |
| Placebo | Change From Baseline in SGRQ Total Score to Week 48 | -5.85 Change from baseline units on a scale |
p-value: 0.104695% CI: [-10.76, 1.01]Mixed Models Analysis
Secondary
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Molgramostim | Change From Baseline in St. Georges Respiratory Questionnaire (SGRQ) Total Score to Week 24 | -11.5 Change from baseline units on a scale |
| Placebo | Change From Baseline in St. Georges Respiratory Questionnaire (SGRQ) Total Score to Week 24 | -4.9 Change from baseline units on a scale |
p-value: 0.007295% CI: [-11.4, -1.79]Mixed Models Analysis
Secondary
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
Population: Some subjects did not have ECG obtained at some visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Molgramostim | Change in QT Interval Corrected by Fridericia (QTcF) | Week 4 | -2.51 msec | Standard Deviation 10.543 |
| Molgramostim | Change in QT Interval Corrected by Fridericia (QTcF) | Week 24 | -1.89 msec | Standard Deviation 13.19 |
| Placebo | Change in QT Interval Corrected by Fridericia (QTcF) | Week 4 | 1.59 msec | Standard Deviation 10.127 |
| Placebo | Change in QT Interval Corrected by Fridericia (QTcF) | Week 24 | -0.96 msec | Standard Deviation 11.534 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Molgramostim | Changes in Forced Expiratory Volume in One Second (FEV1) % Predicted Normal. | Week 24 | 1.2 %predicted normal | Standard Deviation 7.08 |
| Molgramostim | Changes in Forced Expiratory Volume in One Second (FEV1) % Predicted Normal. | Week 48 | 1.4 %predicted normal | Standard Deviation 7.98 |
| Placebo | Changes in Forced Expiratory Volume in One Second (FEV1) % Predicted Normal. | Week 24 | -0.3 %predicted normal | Standard Deviation 5.35 |
| Placebo | Changes in Forced Expiratory Volume in One Second (FEV1) % Predicted Normal. | Week 48 | -1.4 %predicted normal | Standard Deviation 7.56 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Molgramostim | Changes in Forced Vital Capacity (FVC) %Predicted Normal | Week 24 | 3.2 % FVC predicted | Standard Deviation 6.2 |
| Molgramostim | Changes in Forced Vital Capacity (FVC) %Predicted Normal | Week 48 | 3.2 % FVC predicted | Standard Deviation 7.92 |
| Placebo | Changes in Forced Vital Capacity (FVC) %Predicted Normal | Week 24 | 0.9 % FVC predicted | Standard Deviation 5.74 |
| Placebo | Changes in Forced Vital Capacity (FVC) %Predicted Normal | Week 48 | -0.1 % FVC predicted | Standard Deviation 8.27 |
Secondary
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
Population: One subject in the molgramostim group had missing antiGM-CSF titers.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Molgramostim | 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 | Week 24 | 28 Participants |
| Molgramostim | 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 | Week 48 | 39 Participants |
| Placebo | 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 | Week 24 | 30 Participants |
| Placebo | 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 | Week 48 | 37 Participants |
Secondary
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Molgramostim | Number of Subjects With Serious and Non-serious Adverse Events | Any TEAE | 69 participants |
| Molgramostim | Number of Subjects With Serious and Non-serious Adverse Events | Any TESAE | 14 participants |
| Placebo | Number of Subjects With Serious and Non-serious Adverse Events | Any TEAE | 71 participants |
| Placebo | Number of Subjects With Serious and Non-serious Adverse Events | Any TESAE | 20 participants |