Trial Outcomes & Findings for Inhaled GM-CSF Therapy of Autoimmune PAP (NCT NCT00901511)
NCT ID: NCT00901511
Last Updated: 2024-07-12
Results Overview
Time (in months) between the scheduled baseline WLL (at Study Month 0) and the first administration of an unscheduled rescue WLL (during the 30-months after Study Month 0)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
18 participants
Primary outcome timeframe
30 months
Results posted on
2024-07-12
Participant Flow
Participant milestones
| Measure |
Control Group
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without GM-CSF administration, followed by GM-CSF administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Inhaled GM-CSF Therapy of Autoimmune PAP
Baseline characteristics by cohort
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
48 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
36 years
STANDARD_DEVIATION 13 • n=7 Participants
|
42 years
STANDARD_DEVIATION 13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 30 monthsTime (in months) between the scheduled baseline WLL (at Study Month 0) and the first administration of an unscheduled rescue WLL (during the 30-months after Study Month 0)
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Time to Rescue WLL
|
18 Months
Interval 6.0 to 27.0
|
30 Months
Interval 30.0 to 30.0
|
SECONDARY outcome
Timeframe: 30 monthsNumber of patients requiring an unscheduled rescue WLL during the 30-months immediately following administration of the scheduled baseline WLL therapy at Study Month 0.
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Number of Patients Requiring a Rescue WLL
|
7 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 30 monthsPrimary Analysis: Between-group difference in mean PaO2 at each study visit after the scheduled baseline WLL was evaluated using repeated measures analysis of variance (ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary analysis: Between-group difference in mean PaO2 at each visit after imputation of missing data by the last observation carried forward method. For both of the primary and secondary analyses, PaO2 is determined from lab values measured for an arterial blood gas procedure.
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)
Pre-WLL ( Month -1)
|
51 mmHg
Standard Deviation 12
|
66 mmHg
Standard Deviation 14
|
|
Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)
Baseline (Month 0)
|
72 mmHg
Standard Deviation 15
|
82 mmHg
Standard Deviation 11
|
|
Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)
1 month
|
70 mmHg
Standard Deviation 14
|
88 mmHg
Standard Deviation 8.4
|
|
Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)
3 months
|
68 mmHg
Standard Deviation 10
|
89 mmHg
Standard Deviation 9.2
|
|
Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)
6 months
|
73 mmHg
Standard Deviation 11
|
92 mmHg
Standard Deviation 14
|
|
Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)
10 months
|
73 mmHg
Standard Deviation 13
|
92 mmHg
Standard Deviation 12
|
|
Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)
18 months
|
71 mmHg
Standard Deviation 14
|
90 mmHg
Standard Deviation 16
|
|
Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)
30 months
|
71 mmHg
Standard Deviation 14
|
82 mmHg
Standard Deviation 14
|
SECONDARY outcome
Timeframe: 30 monthsPrimary Analysis: Between-group difference in mean A-aDO2 at each study visit after the scheduled baseline WLL was evaluated using repeated measures analysis of variance (ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary analysis: Between-group difference in mean A-aDO2 at each visit after imputation of missing data by the last-value carried forward method. For both of the primary and secondary analyses, A-aDO2 is calculated from lab values measured for an arterial blood gas, the ambient atmosphere pressure, and fraction of inspired oxygen at the time of the arterial blood gas procedure.
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)
Pre-WLL (Month -1)
|
55 mmHg
Standard Deviation 11
|
43 mmHg
Standard Deviation 14
|
|
Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)
Baseline (Month 0)
|
33 mmHg
Standard Deviation 15
|
26 mmHg
Standard Deviation 12
|
|
Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)
1 month
|
37 mmHg
Standard Deviation 17
|
20 mmHg
Standard Deviation 7.2
|
|
Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)
3 months
|
37 mmHg
Standard Deviation 12
|
18 mmHg
Standard Deviation 8.1
|
|
Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)
6 months
|
35 mmHg
Standard Deviation 12
|
15 mmHg
Standard Deviation 12
|
|
Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)
10 months
|
34 mmHg
Standard Deviation 13
|
18 mmHg
Standard Deviation 12
|
|
Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)
18 months
|
35 mmHg
Standard Deviation 13
|
18 mmHg
Standard Deviation 13
|
|
Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)
30 months
|
35 mmHg
Standard Deviation 13
|
24 mmHg
Standard Deviation 13
|
SECONDARY outcome
Timeframe: 30 monthsPrimary Analysis: Between-group difference in mean DLCO at each study visit after the scheduled baseline WLL was evaluated using repeated measures analysis of variance (ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary analysis: Between-group difference in mean DLCO at each visit after imputation of missing data by the last observation carried forward method. For both of the primary and secondary analyses, DLCO is determined from pulmonary function tests.
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)
Pre-WLL (Month -1)
|
38 % predicted
Standard Deviation 14
|
46 % predicted
Standard Deviation 16
|
|
Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)
Baseline (Month 0)
|
50 % predicted
Standard Deviation 14
|
55 % predicted
Standard Deviation 14
|
|
Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)
1 Month
|
55 % predicted
Standard Deviation 13
|
68 % predicted
Standard Deviation 15
|
|
Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)
3 months
|
62 % predicted
Standard Deviation 16
|
72 % predicted
Standard Deviation 17
|
|
Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)
6 months
|
58 % predicted
Standard Deviation 20
|
71 % predicted
Standard Deviation 15
|
|
Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)
10 months
|
59 % predicted
Standard Deviation 20
|
70 % predicted
Standard Deviation 15
|
|
Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)
18 months
|
58 % predicted
Standard Deviation 21
|
71 % predicted
Standard Deviation 17
|
|
Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)
30 months
|
59 % predicted
Standard Deviation 21
|
63 % predicted
Standard Deviation 16
|
SECONDARY outcome
Timeframe: 30 monthsPrimary Analysis: Between-group difference in mean VC at each study visit after the scheduled baseline WLL was evaluated using repeated measures analysis of variance (ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary analysis: Between-group difference in mean VC at each visit after imputation of missing data by the last observation carried forward method. For both of the primary and secondary analyses, VC is determined from pulmonary function tests.
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean Vital Capacity (VC)
Pre-WLL (Month -1)
|
60 % predicted
Standard Deviation 16
|
64 % predicted
Standard Deviation 13
|
|
Between-Group Difference in Mean Vital Capacity (VC)
Baseline (Month 0)
|
74 % predicted
Standard Deviation 11
|
76 % predicted
Standard Deviation 17
|
|
Between-Group Difference in Mean Vital Capacity (VC)
1 month
|
75 % predicted
Standard Deviation 17
|
76 % predicted
Standard Deviation 16
|
|
Between-Group Difference in Mean Vital Capacity (VC)
3 months
|
78 % predicted
Standard Deviation 17
|
80 % predicted
Standard Deviation 15
|
|
Between-Group Difference in Mean Vital Capacity (VC)
6 months
|
78 % predicted
Standard Deviation 15
|
84 % predicted
Standard Deviation 20
|
|
Between-Group Difference in Mean Vital Capacity (VC)
10 months
|
78 % predicted
Standard Deviation 14
|
82 % predicted
Standard Deviation 18
|
|
Between-Group Difference in Mean Vital Capacity (VC)
18 months
|
78 % predicted
Standard Deviation 13
|
83 % predicted
Standard Deviation 21
|
|
Between-Group Difference in Mean Vital Capacity (VC)
30 months
|
77 % predicted
Standard Deviation 13
|
79 % predicted
Standard Deviation 17
|
SECONDARY outcome
Timeframe: 30 monthsPrimary Analysis: Between-group difference in median GGO Score at each study visit after the scheduled baseline WLL was evaluated using repeated measures analysis of variance (ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary analysis: Between-group difference in median GGO Score at each visit after imputation of missing data by the last observation carried forward method. For both of the primary and secondary analyses, the degree of severity of lung disease was calculated by determining the number of segments affected. The following scale was used: Grade 1 = 1 segment affected Grade 2 = 2 - 5 segments affected Grade 3 = 6 - 9 segments affected Grade 4 = 10 - 14 segments affected Grade 5 = \> 14 affected segments
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score
Pre-WLL (Month -1)
|
5 score on a scale
Interval 5.0 to 5.0
|
5 score on a scale
Interval 5.0 to 5.0
|
|
Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score
3 months
|
4 score on a scale
Interval 4.0 to 5.0
|
3 score on a scale
Interval 2.0 to 4.0
|
|
Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score
10 months
|
4 score on a scale
Interval 4.0 to 5.0
|
3 score on a scale
Interval 2.0 to 4.0
|
|
Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score
18 months
|
4 score on a scale
Interval 4.0 to 5.0
|
3 score on a scale
Interval 2.0 to 4.0
|
|
Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score
30 months
|
4 score on a scale
Interval 4.0 to 5.0
|
4 score on a scale
Interval 3.0 to 5.0
|
SECONDARY outcome
Timeframe: 30 monthsPrimary Analysis: Between-group difference in median serum CEA levels at each study visit after the scheduled baseline WLL was evaluated using repeated measures analysis of variance (ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary analysis: Between-group difference in serum CEA levels at each visit after imputation of missing data by the last observation carried forward method. For both of the primary and secondary analyses, the serum CEA levels were determined via enzyme linked immunosorbent assay (ELISA).
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels
Pre-WLL (Month -1)
|
18 ng/ml
Interval 10.0 to 41.0
|
6 ng/ml
Interval 4.0 to 12.0
|
|
Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels
Baseline (Month 0)
|
8 ng/ml
Interval 7.0 to 17.0
|
5 ng/ml
Interval 3.0 to 9.0
|
|
Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels
1 month
|
6 ng/ml
Interval 5.0 to 21.0
|
3 ng/ml
Interval 2.0 to 5.0
|
|
Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels
3 months
|
8 ng/ml
Interval 4.0 to 22.0
|
4 ng/ml
Interval 2.0 to 5.0
|
|
Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels
6 months
|
10 ng/ml
Interval 4.0 to 21.0
|
3 ng/ml
Interval 2.0 to 3.0
|
|
Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels
10 months
|
9 ng/ml
Interval 4.0 to 21.0
|
2 ng/ml
Interval 2.0 to 3.0
|
|
Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels
18 months
|
9 ng/ml
Interval 5.0 to 19.0
|
3 ng/ml
Interval 2.0 to 4.0
|
|
Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels
30 months
|
8 ng/ml
Interval 5.0 to 19.0
|
5 ng/ml
Interval 3.0 to 5.0
|
SECONDARY outcome
Timeframe: 30 monthsPrimary Analysis: Between-group difference in median serum KL-6 levels at each study visit after the scheduled baseline WLL was evaluated using repeated measures analysis of variance (ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary analysis: Between-group difference in serum KL-6 levels at each visit after imputation of missing data by the last observation carried forward method. For both of the primary and secondary analyses, the serum KL-6 levels were determined via enzyme linked immunosorbent assay (ELISA).
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels
Pre-WLL (Month -1)
|
9023 U/ml
Interval 6660.0 to 19205.0
|
5758 U/ml
Interval 3247.0 to 7759.0
|
|
Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels
Baseline (Month 0)
|
10556 U/ml
Interval 6501.0 to 18734.0
|
5538 U/ml
Interval 1738.0 to 7287.0
|
|
Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels
1 month
|
8744 U/ml
Interval 6340.0 to 14413.0
|
2401 U/ml
Interval 1348.0 to 14828.0
|
|
Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels
3 months
|
6524 U/ml
Interval 2296.0 to 18562.0
|
2422 U/ml
Interval 718.0 to 11473.0
|
|
Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels
6 months
|
8934 U/ml
Interval 808.0 to 13494.0
|
2117 U/ml
Interval 648.0 to 29300.0
|
|
Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels
10 months
|
8116 U/ml
Interval 712.0 to 14141.0
|
6546 U/ml
Interval 1218.0 to 13697.0
|
|
Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels
18 months
|
7314 U/ml
Interval 1714.0 to 11335.0
|
3114 U/ml
Interval 1330.0 to 5742.0
|
|
Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels
30 months
|
5755 U/ml
Interval 1714.0 to 8257.0
|
1448 U/ml
Interval 666.0 to 8539.0
|
SECONDARY outcome
Timeframe: 30 monthsPrimary Analysis: Between-group difference in mean serum Cyfra21.1 levels at each study visit after the scheduled baseline WLL was evaluated using repeated measures analysis of variance (ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary analysis: Between-group difference in serum Cyfra21.1 levels at each visit after imputation of missing data by the last observation carried forward method. For both of the primary and secondary analyses, the serum Cyfra21.1 levels were determined via enzyme linked immunosorbent assay (ELISA).
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels
Pre-WLL (Month -1)
|
27 ng/ml
Standard Deviation 17
|
13 ng/ml
Standard Deviation 8
|
|
Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels
Baseline (Month 0)
|
10 ng/ml
Standard Deviation 6
|
6 ng/ml
Standard Deviation 2
|
|
Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels
1 month
|
11 ng/ml
Standard Deviation 7
|
5 ng/ml
Standard Deviation 2
|
|
Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels
3 months
|
10 ng/ml
Standard Deviation 5
|
5 ng/ml
Standard Deviation 2
|
|
Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels
6 months
|
9 ng/ml
Standard Deviation 7
|
4 ng/ml
Standard Deviation 2
|
|
Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels
10 months
|
9 ng/ml
Standard Deviation 6
|
4 ng/ml
Standard Deviation 2
|
|
Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels
18 months
|
8 ng/ml
Standard Deviation 7
|
4 ng/ml
Standard Deviation 2
|
|
Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels
30 months
|
8 ng/ml
Standard Deviation 7
|
5 ng/ml
Standard Deviation 2
|
SECONDARY outcome
Timeframe: 30 monthsAnalysis Method: Between-group difference in serum GMAb levels at each visit after imputation of missing data by the last observation carried forward method. The serum GMAb levels were determined via enzyme linked immunosorbent assay (ELISA).
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels
Pre-WLL (Month -1)
|
23 mcg/ml
Interval 11.0 to 47.0
|
32 mcg/ml
Interval 18.0 to 59.0
|
|
Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels
Baseline (Month 0)
|
20 mcg/ml
Interval 9.0 to 27.0
|
28 mcg/ml
Interval 19.0 to 61.0
|
|
Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels
1 month
|
25 mcg/ml
Interval 12.0 to 48.0
|
30 mcg/ml
Interval 17.0 to 59.0
|
|
Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels
3 months
|
27 mcg/ml
Interval 10.0 to 47.0
|
34 mcg/ml
Interval 26.0 to 62.0
|
|
Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels
6 months
|
22 mcg/ml
Interval 10.0 to 54.0
|
36 mcg/ml
Interval 23.0 to 51.0
|
|
Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels
10 months
|
22 mcg/ml
Interval 10.0 to 51.0
|
33 mcg/ml
Interval 21.0 to 41.0
|
|
Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels
18 months
|
19 mcg/ml
Interval 9.0 to 50.0
|
24 mcg/ml
Interval 15.0 to 32.0
|
|
Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels
30 months
|
19 mcg/ml
Interval 9.0 to 50.0
|
12 mcg/ml
Interval 9.0 to 33.0
|
SECONDARY outcome
Timeframe: 30 monthsAnalysis Method: Between-group difference in WBC counts at each visit after imputation of missing data by the last observation carried forward method. The WBC counts were determined via complete blood count.
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean White Blood Cell (WBC) Counts
Pre-WLL (Month -1)
|
7.7 x10^6 cells/ml
Standard Deviation 1.8
|
6.2 x10^6 cells/ml
Standard Deviation 1.2
|
|
Between-Group Difference in Mean White Blood Cell (WBC) Counts
Baseline (Month 0)
|
7.5 x10^6 cells/ml
Standard Deviation 1.7
|
8.7 x10^6 cells/ml
Standard Deviation 2.7
|
|
Between-Group Difference in Mean White Blood Cell (WBC) Counts
1 month
|
6.8 x10^6 cells/ml
Standard Deviation 1.6
|
6.4 x10^6 cells/ml
Standard Deviation 1.6
|
|
Between-Group Difference in Mean White Blood Cell (WBC) Counts
3 months
|
6.8 x10^6 cells/ml
Standard Deviation 1.4
|
5.9 x10^6 cells/ml
Standard Deviation 1.1
|
|
Between-Group Difference in Mean White Blood Cell (WBC) Counts
6 months
|
6.8 x10^6 cells/ml
Standard Deviation 1.6
|
6.2 x10^6 cells/ml
Standard Deviation 1.3
|
|
Between-Group Difference in Mean White Blood Cell (WBC) Counts
10 months
|
67 x10^6 cells/ml
Standard Deviation 1.8
|
6.1 x10^6 cells/ml
Standard Deviation 1.1
|
|
Between-Group Difference in Mean White Blood Cell (WBC) Counts
18 months
|
6.8 x10^6 cells/ml
Standard Deviation 1.6
|
6.5 x10^6 cells/ml
Standard Deviation 10
|
|
Between-Group Difference in Mean White Blood Cell (WBC) Counts
30 months
|
6.8 x10^6 cells/ml
Standard Deviation 1.6
|
6.1 x10^6 cells/ml
Standard Deviation 1.5
|
SECONDARY outcome
Timeframe: 30 monthsAnalysis Method: Between-group difference in platelet counts at each visit after imputation of missing data by the last observation carried forward method. The platelet counts were determined via complete blood count.
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean Platelet Counts
6 months
|
267 x10^6 cells/ml
Standard Deviation 42
|
238 x10^6 cells/ml
Standard Deviation 45
|
|
Between-Group Difference in Mean Platelet Counts
10 months
|
269 x10^6 cells/ml
Standard Deviation 50
|
242 x10^6 cells/ml
Standard Deviation 49
|
|
Between-Group Difference in Mean Platelet Counts
30 months
|
263 x10^6 cells/ml
Standard Deviation 53
|
232 x10^6 cells/ml
Standard Deviation 46
|
|
Between-Group Difference in Mean Platelet Counts
18 months
|
263 x10^6 cells/ml
Standard Deviation 54
|
236 x10^6 cells/ml
Standard Deviation 42
|
|
Between-Group Difference in Mean Platelet Counts
Pre-WLL (Month -1)
|
289 x10^6 cells/ml
Standard Deviation 96
|
236 x10^6 cells/ml
Standard Deviation 56
|
|
Between-Group Difference in Mean Platelet Counts
Baseline (Month 0)
|
290 x10^6 cells/ml
Standard Deviation 111
|
269 x10^6 cells/ml
Standard Deviation 73
|
|
Between-Group Difference in Mean Platelet Counts
1 month
|
266 x10^6 cells/ml
Standard Deviation 57
|
248 x10^6 cells/ml
Standard Deviation 46
|
|
Between-Group Difference in Mean Platelet Counts
3 months
|
280 x10^6 cells/ml
Standard Deviation 83
|
252 x10^6 cells/ml
Standard Deviation 42
|
SECONDARY outcome
Timeframe: 30 monthsPrimary Analysis: Between-group difference in mean SF-36 General Health Score at each study visit after the scheduled baseline WLL was evaluated using repeated measures analysis of variance (ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary analysis: Between-group difference in SF-36 General Health Score at each visit after imputation of missing data by the last observation carried forward method. The SF-36 General Health Score were determined from the RAND 36-Item Health Survey. Scoring the SF-36 questionnaire is a two-step process. First, pre-coded numeric values are recoded per the scoring key. All items are scored on a scale of 0 to 100 so that a high score defines a more favorable health state. Scores represent the percentage of total possible score achieved. In step 2, General Health is determined from the average score for questions 1, 33, 34, 35, and 36.
Outcome measures
| Measure |
Control Group
n=9 Participants
All participants received a scheduled bilateral whole lung lavage (WLL) at baseline (month 0). Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of pulmonary alveolar proteinosis (PAP) lung disease as defined in the protocol.
|
GM-CSF Group
n=9 Participants
All participants received a scheduled bilateral WLL at baseline (month 0). All participants received inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) (Sargramostim, 250 mcg) administered once daily every other week for 12 consecutive weeks, followed by a 4-week washout period without administration, followed by administration on days 1 and 3 of every consecutive 14-day period for 6 months. Unscheduled rescue WLL was administered, as required, to any participant who experienced progression of PAP lung disease as defined in the protocol.
|
|---|---|---|
|
Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score
Pre-WLL (Month -1)
|
44 Score on a scale
Standard Deviation 27
|
39 Score on a scale
Standard Deviation 22
|
|
Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score
1 month
|
77 Score on a scale
Standard Deviation 20
|
85 Score on a scale
Standard Deviation 15
|
|
Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score
3 months
|
79 Score on a scale
Standard Deviation 18
|
93 Score on a scale
Standard Deviation 6.1
|
|
Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score
6 months
|
77 Score on a scale
Standard Deviation 22
|
95 Score on a scale
Standard Deviation 4.3
|
|
Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score
10 months
|
72 Score on a scale
Standard Deviation 26
|
84 Score on a scale
Standard Deviation 15
|
|
Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score
18 months
|
74 Score on a scale
Standard Deviation 26
|
84 Score on a scale
Standard Deviation 18
|
|
Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score
30 months
|
71 Score on a scale
Standard Deviation 28
|
88 Score on a scale
Standard Deviation 8.7
|
Adverse Events
Control Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
GM-CSF Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Francesca Mariani
Fondazione IRCCS Policlinico San Matteo Pavia
Phone: +39 0382 503590
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place