Autoimmune Pulmonary Alveolar Proteinosis
Conditions
Keywords
Whole lung lavage, GM-CSF, Sargramostim, aPAP
Brief summary
This is a prospective, randomized, open-label, long-term, phase 2 study of inhaled granulocyte/macrophage-colony stimulating factor following whole lung lavage therapy in patients with autoimmune pulmonary alveolar proteinosis.
Detailed description
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disorder of progressive surfactant accumulation and resulting hypoxemic respiratory failure caused by disruption of granulocyte/macrophage-colony stimulating factor (GM-CSF) signaling, which alveolar macrophages require to remove pulmonary surfactant. The current therapy of aPAP, whole lung lavage (WLL), is a procedure requiring general anesthesia, endotracheal intubation to isolate each lung, and mechanical ventilation of the untreated lung while the treated lung repeatedly filled with saline and drained while percussing the chest to loosen and emulsify the surfactant and saline to physically remove the excess surfactant. Inhaled GM-CSF is a promising pharmacotherapeutic approach shown in case reports, small series, moderate open-label studies, and two randomized, double-blinded, placebo-controlled trials to be safe and improve the clinical, physiological, radiological, and biochemical disease manifestations in patients with mild-moderate aPAP. In contrast to the present study, prior studies were too short in duration to permit an evaluation on the requirement for WLL, which aPAP patients require a mean of every 15 months. The present study addressed the effects on WLL by studying patients with moderate-severe aPAP and by utilizing a long-term follow up period. The study design included a screening visit (month -3) to establish eligibility, an observation period (-3 to 0 months) to establish the presence of progressive/unremitting aPAP and establish disease severity, a pre-WLL visit (-1 month), a baseline visit (month 0) during which all patients received a scheduled, baseline, bilateral WLL, a 10-month, open-label treatment period, and a 20-month follow-up period. Study visits were scheduled at months -3, -1, 0, 1, 3, 6, 10, 18, and 30 months. Patients were randomized by the statistician to the GM-CSF Group (n=9) or the Control Group (n=9). Investigators were blinded to group assignment until after the participant's baseline visit. Patients randomized to the GM-CSF group (n=9) received inhaled GM-CSF (sargramostim (Leukine®), 250 mcg daily every other week for 12 weeks beginning 1 week after the baseline WLL - termed GM-CSF induction therapy period, followed by a 4-week washout period during which no GM-CSF was administered), and then received inhaled GM-CSF (sargramostim, 250 mcg/day on days 1 and 3 of every 14-day period for 6 months - termed GM-CSF maintenance therapy period). Inhaled GM-CSF (Leukine®) was administered using AKITA2 APIXNEB nebulizer system (Activaero, Vectura GmbH, Germany). Patients randomized to the Control Group (n=9) received no further scheduled treatment. Any patient in either group experiencing with disease progression resulting in respiratory failure (defined as peripheral artery oxygen concentration (PaO2) \<60 mmHg at rest or PaO2 \>60 mmHg at rest AND a peripheral blood oxygen saturation (SpO2) \< 90% OR a decline in SpO2 of 5% or more during exercise), received (unscheduled) rescue WLL and were considered to have failed their assigned intervention (GM-CSF or Control). The primary outcome measure was time, in months, between the scheduled baseline WLL and first administration of unscheduled 'rescue' WLL (termed 'time to rescue WLL'). Key secondary outcome measures included the response in peripheral arterial oxygen concentration (PaO2), alveolar-arterial difference in oxygen concentration (A-aDO2), diffusing capacity of the lungs for carbon monoxide (DLco), vital capacity, ground glass opacification (GGO) of the lungs measured by visual scoring of chest computed tomography (CT) scans, and serum biomarkers of PAP (carcinoembryonic antigen, Krebs von-Lungren antigen, Cyfra-21.1). Other outcome measures included the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), serum GM-CSF autoantibody concentration, the peripheral white blood cell and platelet counts. The occurrence and timing of rescue WLL administration in each group was evaluated using Kaplan-Meyer analysis. The primary end point was analyzed as the difference in median time to rescue WLL between the GM-CSF group and the Control group. Categorical outcomes were compared using Fisher's exact test. Key secondary end points were evaluated using repeated measures analysis of variance (RM-ANOVA) after adjustment for baseline values, gender, age, and the number of patients at risk at each time point. Secondary outcome measures were also evaluated by comparing the between-group mean (or median) values at each visit using Student's t-test (or Mann-Whitney test) after imputation of missing data using a last observation carried forward approach to reduce selection-type bias by comparing the corresponding group means or medians. All reported p values are two-sided and have not been adjusted for multiple testing. P values of less than 0.05 were considered to indicate statistical significance. Analysis of the primary and key secondary outcomes was performed with the use of Stata software version 14.2. Analyses of secondary outcome measures were performed with the use of Prism for Mac OS software, version 9.51. Anticipated results were intended to compare the effects of inhaled GM-CSF following baseline WLL to those of baseline WLL alone in patients with moderate to severe aPAP.
Interventions
PROCEDUREBaseline WLL
Scheduled bilateral WLL
DRUGSargramostim
Inhaled GM-CSF
PROCEDURERescue WLL
Unscheduled bilateral WLL
Sponsors
Agenzia Italiana del Farmaco
Fondazione IRCCS Policlinico San Matteo di Pavia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female of male 18 years of age or older * Diagnosis of autoimmune PAP * Able and willing to provide written informed consent * Eligible for whole lung lavage determined as the presence of persistent or progressive respiratory failure (PaO2 at rest \< 60 mm Hg) or desaturation \< 90% or \> 5 percentage points during standard exercise
Exclusion criteria
* Diagnosis with secondary PAP, congenital PAP, or hereditary PAP * Contraindication to whole lung lavage * Contraindication to administration of inhaled GM-CSF * Chronic lung disease associated with already existing respiratory failure, such as emphysema or pulmonary fibrosis, chronic heart failure, ischemic heart disease, active pulmonary embolism, progressive cancer, and other severe metabolic conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Rescue WLL | 30 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 30 months | Primary 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. |
| Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 30 months | Primary 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. |
| Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 30 months | Primary 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. |
| Between-Group Difference in Mean Vital Capacity (VC) | 30 months | Primary 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. |
| Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | 30 months | Primary 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 |
| Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 30 months | Primary 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). |
| Number of Patients Requiring a Rescue WLL | 30 months | Number of patients requiring an unscheduled rescue WLL during the 30-months immediately following administration of the scheduled baseline WLL therapy at Study Month 0. |
| Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 30 months | Primary 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). |
| Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 30 months | Analysis 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). |
| Between-Group Difference in Mean White Blood Cell (WBC) Counts | 30 months | Analysis 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. |
| Between-Group Difference in Mean Platelet Counts | 30 months | Analysis 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. |
| Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score | 30 months | Primary 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. |
| Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 30 months | Primary 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). |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| 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 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. | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | Control Group | GM-CSF Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 18 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 9.2 | 36 years STANDARD_DEVIATION 13 | 42 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 9 Participants | 17 Participants |
| Region of Enrollment Italy | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 0 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 |
Outcome results
Primary
Time to Rescue WLL
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)
Time frame: 30 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Group | Time to Rescue WLL | 18 Months |
| GM-CSF Group | Time to Rescue WLL | 30 Months |
p-value: 0.0078Wilcoxon (Mann-Whitney)
Secondary
Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score
Primary 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.
Time frame: 30 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | 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 |
| Control Group | 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 |
| Control Group | 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 |
| Control Group | 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 |
| Control Group | 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 |
| Control Group | 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 |
| Control Group | 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 |
| GM-CSF Group | Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score | 30 months | 88 Score on a scale | Standard Deviation 8.7 |
| GM-CSF Group | Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score | Pre-WLL (Month -1) | 39 Score on a scale | Standard Deviation 22 |
| GM-CSF Group | Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score | 1 month | 85 Score on a scale | Standard Deviation 15 |
| GM-CSF Group | Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score | 3 months | 93 Score on a scale | Standard Deviation 6.1 |
| GM-CSF Group | Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score | 6 months | 95 Score on a scale | Standard Deviation 4.3 |
| GM-CSF Group | Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score | 10 months | 84 Score on a scale | Standard Deviation 15 |
| GM-CSF Group | Between-Group Difference in Mean 36-Item Short Form Survey (SF-36) General Health Score | 18 months | 84 Score on a scale | Standard Deviation 18 |
Comparison: Primary analysisp-value: 0.14995% CI: [-1.88, 11.33]Repeated measures ANOVA
Comparison: The secondary analysis includes evaluation of the difference in mean SF-36 General Health Score between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.726395% CI: [-30.04, 21.43]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in SF-36 General Health Score between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.329895% CI: [-9.24, 25.91]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in SF-36 General Health Score between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.047895% CI: [-0.15, 27.62]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean SF-36 General Health Score between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.028195% CI: [2.16, 33.39]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean SF-36 General Health Score between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.263495% CI: [-9.67, 33]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean SF-36 General Health Score between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.354895% CI: [-12.24, 32.24]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean SF-36 General Health Score between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.104395% CI: [-3.85, 37.18]t-test, 2 sided
Secondary
Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)
Primary 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.
Time frame: 30 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | Pre-WLL (Month -1) | 55 mmHg | Standard Deviation 11 |
| Control Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 6 months | 35 mmHg | Standard Deviation 12 |
| Control Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 1 month | 37 mmHg | Standard Deviation 17 |
| Control Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 10 months | 34 mmHg | Standard Deviation 13 |
| Control Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | Baseline (Month 0) | 33 mmHg | Standard Deviation 15 |
| Control Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 18 months | 35 mmHg | Standard Deviation 13 |
| Control Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 3 months | 37 mmHg | Standard Deviation 12 |
| Control Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 30 months | 35 mmHg | Standard Deviation 13 |
| GM-CSF Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 3 months | 18 mmHg | Standard Deviation 8.1 |
| GM-CSF Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | Pre-WLL (Month -1) | 43 mmHg | Standard Deviation 14 |
| GM-CSF Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | Baseline (Month 0) | 26 mmHg | Standard Deviation 12 |
| GM-CSF Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 1 month | 20 mmHg | Standard Deviation 7.2 |
| GM-CSF Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 30 months | 24 mmHg | Standard Deviation 13 |
| GM-CSF Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 6 months | 15 mmHg | Standard Deviation 12 |
| GM-CSF Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 10 months | 18 mmHg | Standard Deviation 12 |
| GM-CSF Group | Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2) | 18 months | 18 mmHg | Standard Deviation 13 |
Comparison: The secondary analysis includes evaluation of the difference in mean A-aDO2 between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.015295% CI: [-28.23, -3.48]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean A-aDO2 between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.015495% CI: [-30.31, -3.71]t-test, 2 sided
Comparison: Primary analysisp-value: <0.000195% CI: [-14.8, -5.4]Repeated measures ANOVA
Comparison: The secondary analysis includes evaluation of the difference in mean A-aDO2 between groups at the pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.054595% CI: [-25.19, 0.27]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean A-aDO2 between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.280295% CI: [-20.52, 6.35]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean A-aDO2 between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.014895% CI: [-29.85, -3.76]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean A-aDO2 between groups at the 3 -month visit after imputation of missing data using a last observation carried forward method.p-value: 0.001595% CI: [-29.18, -8.36]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean A-aDO2 between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.004995% CI: [-31.49, -6.7]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean A-aDO2 between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.092195% CI: [-24.05, 2.02]t-test, 2 sided
Secondary
Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score
Primary 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
Time frame: 30 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | 3 months | 4 score on a scale |
| Control Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | 18 months | 4 score on a scale |
| Control Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | Pre-WLL (Month -1) | 5 score on a scale |
| Control Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | 30 months | 4 score on a scale |
| Control Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | 10 months | 4 score on a scale |
| GM-CSF Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | 30 months | 4 score on a scale |
| GM-CSF Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | 3 months | 3 score on a scale |
| GM-CSF Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | 10 months | 3 score on a scale |
| GM-CSF Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | 18 months | 3 score on a scale |
| GM-CSF Group | Between-Group Difference in Mean Chest Computed Tomography Ground Glass Opacification (GGO) Score | Pre-WLL (Month -1) | 5 score on a scale |
Comparison: Primary Analysisp-value: 0.05395% CI: [-1.7, 0.01]Repeated measures ANOVA
Comparison: The secondary analysis includes evaluation of the difference in median GGO Score between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: >0.9999Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median GGO Score between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.0332Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median GGO Score between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.0676Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median GGO Score between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.0629Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median GGO Score between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: >0.9999Wilcoxon (Mann-Whitney)
Secondary
Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)
Primary 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.
Time frame: 30 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | Pre-WLL (Month -1) | 38 % predicted | Standard Deviation 14 |
| Control Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 6 months | 58 % predicted | Standard Deviation 20 |
| Control Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 1 Month | 55 % predicted | Standard Deviation 13 |
| Control Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | Baseline (Month 0) | 50 % predicted | Standard Deviation 14 |
| Control Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 18 months | 58 % predicted | Standard Deviation 21 |
| Control Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 3 months | 62 % predicted | Standard Deviation 16 |
| Control Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 30 months | 59 % predicted | Standard Deviation 21 |
| Control Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 10 months | 59 % predicted | Standard Deviation 20 |
| GM-CSF Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 30 months | 63 % predicted | Standard Deviation 16 |
| GM-CSF Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | Pre-WLL (Month -1) | 46 % predicted | Standard Deviation 16 |
| GM-CSF Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | Baseline (Month 0) | 55 % predicted | Standard Deviation 14 |
| GM-CSF Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 1 Month | 68 % predicted | Standard Deviation 15 |
| GM-CSF Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 3 months | 72 % predicted | Standard Deviation 17 |
| GM-CSF Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 6 months | 71 % predicted | Standard Deviation 15 |
| GM-CSF Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 10 months | 70 % predicted | Standard Deviation 15 |
| GM-CSF Group | Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) | 18 months | 71 % predicted | Standard Deviation 17 |
Comparison: Primary Analysisp-value: 0.02295% CI: [1.9, 21.3]Repeated measures ANOVA
Comparison: The secondary analysis includes evaluation of the difference in mean DLCO between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.318695% CI: [-9.06, 25.63]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean DLCO between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.411195% CI: [-8.4, 19.51]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean DLCO between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.065895% CI: [-0.95, 26.73]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean DLCO between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.228795% CI: [-6.78, 26.34]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean DLCO between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.143295% CI: [-4.86, 30.64]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean DLCO between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.183395% CI: [-6.17, 29.73]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean DLCO between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.188895% CI: [-6.9, 32.23]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean DLCO between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.637495% CI: [-14.41, 22.85]t-test, 2 sided
Secondary
Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)
Primary 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.
Time frame: 30 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 6 months | 73 mmHg | Standard Deviation 11 |
| Control Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | Pre-WLL ( Month -1) | 51 mmHg | Standard Deviation 12 |
| Control Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 10 months | 73 mmHg | Standard Deviation 13 |
| Control Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 1 month | 70 mmHg | Standard Deviation 14 |
| Control Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 18 months | 71 mmHg | Standard Deviation 14 |
| Control Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | Baseline (Month 0) | 72 mmHg | Standard Deviation 15 |
| Control Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 30 months | 71 mmHg | Standard Deviation 14 |
| Control Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 3 months | 68 mmHg | Standard Deviation 10 |
| GM-CSF Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 30 months | 82 mmHg | Standard Deviation 14 |
| GM-CSF Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | Pre-WLL ( Month -1) | 66 mmHg | Standard Deviation 14 |
| GM-CSF Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | Baseline (Month 0) | 82 mmHg | Standard Deviation 11 |
| GM-CSF Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 1 month | 88 mmHg | Standard Deviation 8.4 |
| GM-CSF Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 6 months | 92 mmHg | Standard Deviation 14 |
| GM-CSF Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 10 months | 92 mmHg | Standard Deviation 12 |
| GM-CSF Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 18 months | 90 mmHg | Standard Deviation 16 |
| GM-CSF Group | Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2) | 3 months | 89 mmHg | Standard Deviation 9.2 |
p-value: <0.000195% CI: [5.7, 13.3]Repeated measures ANOVA
Comparison: The secondary analysis includes evaluation of the difference in mean PaO2 between groups at the pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.026195% CI: [2.04, 28.16]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean PaO2 between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.152195% CI: [3.92, 23.03]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean PaO2 between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.005195% CI: [6.26, 29.82]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean PaO2 between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.000495% CI: [10.63, 29.88]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean PaO2 between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.003895% CI: [7.43, 32.4]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean PaO2 between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.014995% CI: [3.81, 30.03]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean PaO2 between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.014895% CI: [4.26, 33.79]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean PaO2 between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.115895% CI: [-3.02, 25.02]t-test, 2 sided
Secondary
Between-Group Difference in Mean Platelet Counts
Analysis 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.
Time frame: 30 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Between-Group Difference in Mean Platelet Counts | Pre-WLL (Month -1) | 289 x10^6 cells/ml | Standard Deviation 96 |
| Control Group | Between-Group Difference in Mean Platelet Counts | 30 months | 263 x10^6 cells/ml | Standard Deviation 53 |
| Control Group | Between-Group Difference in Mean Platelet Counts | Baseline (Month 0) | 290 x10^6 cells/ml | Standard Deviation 111 |
| Control Group | Between-Group Difference in Mean Platelet Counts | 1 month | 266 x10^6 cells/ml | Standard Deviation 57 |
| Control Group | Between-Group Difference in Mean Platelet Counts | 3 months | 280 x10^6 cells/ml | Standard Deviation 83 |
| Control Group | Between-Group Difference in Mean Platelet Counts | 6 months | 267 x10^6 cells/ml | Standard Deviation 42 |
| Control Group | Between-Group Difference in Mean Platelet Counts | 10 months | 269 x10^6 cells/ml | Standard Deviation 50 |
| Control Group | Between-Group Difference in Mean Platelet Counts | 18 months | 263 x10^6 cells/ml | Standard Deviation 54 |
| GM-CSF Group | Between-Group Difference in Mean Platelet Counts | 30 months | 232 x10^6 cells/ml | Standard Deviation 46 |
| GM-CSF Group | Between-Group Difference in Mean Platelet Counts | 18 months | 236 x10^6 cells/ml | Standard Deviation 42 |
| GM-CSF Group | Between-Group Difference in Mean Platelet Counts | 3 months | 252 x10^6 cells/ml | Standard Deviation 42 |
| GM-CSF Group | Between-Group Difference in Mean Platelet Counts | Pre-WLL (Month -1) | 236 x10^6 cells/ml | Standard Deviation 56 |
| GM-CSF Group | Between-Group Difference in Mean Platelet Counts | 10 months | 242 x10^6 cells/ml | Standard Deviation 49 |
| GM-CSF Group | Between-Group Difference in Mean Platelet Counts | Baseline (Month 0) | 269 x10^6 cells/ml | Standard Deviation 73 |
| GM-CSF Group | Between-Group Difference in Mean Platelet Counts | 6 months | 238 x10^6 cells/ml | Standard Deviation 45 |
| GM-CSF Group | Between-Group Difference in Mean Platelet Counts | 1 month | 248 x10^6 cells/ml | Standard Deviation 46 |
Comparison: The secondary analysis includes evaluation of the difference in mean platelet counts between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.186495% CI: [-136.4, 28.96]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean platelet counts between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.654195% CI: [-119.8, 77.51]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean platelet counts between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.45695% CI: [-70.89, 33.33]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean platelet counts between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.372195% CI: [-94.12, 37.23]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean platelet counts between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.181295% CI: [-72.41, 14.86]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean platelet counts between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.280595% CI: [-75.67, 23.44]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean platelet counts between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.24795% CI: [-75.56, 20.89]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean platelet counts between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.20795% CI: [-80.97, 18.97]t-test, 2 sided
Secondary
Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels
Primary 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).
Time frame: 30 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | Pre-WLL (Month -1) | 27 ng/ml | Standard Deviation 17 |
| Control Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | Baseline (Month 0) | 10 ng/ml | Standard Deviation 6 |
| Control Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 1 month | 11 ng/ml | Standard Deviation 7 |
| Control Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 3 months | 10 ng/ml | Standard Deviation 5 |
| Control Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 6 months | 9 ng/ml | Standard Deviation 7 |
| Control Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 10 months | 9 ng/ml | Standard Deviation 6 |
| Control Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 18 months | 8 ng/ml | Standard Deviation 7 |
| Control Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 30 months | 8 ng/ml | Standard Deviation 7 |
| GM-CSF Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 30 months | 5 ng/ml | Standard Deviation 2 |
| GM-CSF Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | Pre-WLL (Month -1) | 13 ng/ml | Standard Deviation 8 |
| GM-CSF Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 6 months | 4 ng/ml | Standard Deviation 2 |
| GM-CSF Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | Baseline (Month 0) | 6 ng/ml | Standard Deviation 2 |
| GM-CSF Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 18 months | 4 ng/ml | Standard Deviation 2 |
| GM-CSF Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 1 month | 5 ng/ml | Standard Deviation 2 |
| GM-CSF Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 10 months | 4 ng/ml | Standard Deviation 2 |
| GM-CSF Group | Between-Group Difference in Mean Serum Cytokeratin-19 Fragment (Cyfra21.1) Levels | 3 months | 5 ng/ml | Standard Deviation 2 |
Comparison: Primary Analysisp-value: 0.2295% CI: [-0.44, -0.04]Repeated measures ANOVA
Comparison: •The secondary analysis includes evaluation of the difference in mean serum Cyfra21.1 levels between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.05695% CI: [-28.8, 0.42]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean serum Cyfra21.1 levels between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.064895% CI: [-8.8, 0.29]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean serum Cyfra21.1 levels between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.017595% CI: [-11.28, -1.25]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean serum Cyfra21.1 levels between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.014895% CI: [-29.85, -3.76]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean serum Cyfra21.1 levels between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.008995% CI: [-9.27, -1.56]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean serum Cyfra21.1 levels between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.034395% CI: [-9.92, -0.43]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean serum Cyfra21.1 levels between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.087195% CI: [-9.21, 0.69]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean serum Cyfra21.1 levels between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.226595% CI: [-8.09, 2.06]t-test, 2 sided
Secondary
Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels
Primary 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).
Time frame: 30 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | Pre-WLL (Month -1) | 9023 U/ml |
| Control Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 6 months | 8934 U/ml |
| Control Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 1 month | 8744 U/ml |
| Control Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 10 months | 8116 U/ml |
| Control Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | Baseline (Month 0) | 10556 U/ml |
| Control Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 18 months | 7314 U/ml |
| Control Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 3 months | 6524 U/ml |
| Control Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 30 months | 5755 U/ml |
| GM-CSF Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 3 months | 2422 U/ml |
| GM-CSF Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | Pre-WLL (Month -1) | 5758 U/ml |
| GM-CSF Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | Baseline (Month 0) | 5538 U/ml |
| GM-CSF Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 1 month | 2401 U/ml |
| GM-CSF Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 30 months | 1448 U/ml |
| GM-CSF Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 6 months | 2117 U/ml |
| GM-CSF Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 10 months | 6546 U/ml |
| GM-CSF Group | Between-Group Difference in Mean Serum Krebs Von-Lungren 6 Antigen (KL-6) Levels | 18 months | 3114 U/ml |
Comparison: Primary Analysisp-value: 0.0395% CI: [-6972, -406]Repeated measures ANOVA
Comparison: The secondary analysis includes evaluation of the difference in median serum KL-6 levels between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.077Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum KL-6 levels between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.0745Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum KL-6 levels between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.2581Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum KL-6 levels between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.4894Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum KL-6 levels between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: >0.9999Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum KL-6 levels between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.8633Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum KL-6 levels between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.3401Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum KL-6 levels between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.2973Wilcoxon (Mann-Whitney)
Secondary
Between-Group Difference in Mean Vital Capacity (VC)
Primary 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.
Time frame: 30 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Between-Group Difference in Mean Vital Capacity (VC) | 3 months | 78 % predicted | Standard Deviation 17 |
| Control Group | Between-Group Difference in Mean Vital Capacity (VC) | Baseline (Month 0) | 74 % predicted | Standard Deviation 11 |
| Control Group | Between-Group Difference in Mean Vital Capacity (VC) | 6 months | 78 % predicted | Standard Deviation 15 |
| Control Group | Between-Group Difference in Mean Vital Capacity (VC) | Pre-WLL (Month -1) | 60 % predicted | Standard Deviation 16 |
| Control Group | Between-Group Difference in Mean Vital Capacity (VC) | 18 months | 78 % predicted | Standard Deviation 13 |
| Control Group | Between-Group Difference in Mean Vital Capacity (VC) | 1 month | 75 % predicted | Standard Deviation 17 |
| Control Group | Between-Group Difference in Mean Vital Capacity (VC) | 30 months | 77 % predicted | Standard Deviation 13 |
| Control Group | Between-Group Difference in Mean Vital Capacity (VC) | 10 months | 78 % predicted | Standard Deviation 14 |
| GM-CSF Group | Between-Group Difference in Mean Vital Capacity (VC) | 30 months | 79 % predicted | Standard Deviation 17 |
| GM-CSF Group | Between-Group Difference in Mean Vital Capacity (VC) | Pre-WLL (Month -1) | 64 % predicted | Standard Deviation 13 |
| GM-CSF Group | Between-Group Difference in Mean Vital Capacity (VC) | Baseline (Month 0) | 76 % predicted | Standard Deviation 17 |
| GM-CSF Group | Between-Group Difference in Mean Vital Capacity (VC) | 1 month | 76 % predicted | Standard Deviation 16 |
| GM-CSF Group | Between-Group Difference in Mean Vital Capacity (VC) | 3 months | 80 % predicted | Standard Deviation 15 |
| GM-CSF Group | Between-Group Difference in Mean Vital Capacity (VC) | 10 months | 82 % predicted | Standard Deviation 18 |
| GM-CSF Group | Between-Group Difference in Mean Vital Capacity (VC) | 18 months | 83 % predicted | Standard Deviation 21 |
| GM-CSF Group | Between-Group Difference in Mean Vital Capacity (VC) | 6 months | 84 % predicted | Standard Deviation 20 |
Comparison: Primary Analysisp-value: 0.53295% CI: [-5.3, 9.9]Repeated measures ANOVA
Comparison: The secondary analysis includes evaluation of the difference in mean VC between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.677295% CI: [-13.09, 19.52]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean VC between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.83295% CI: [-12.52, 15.64]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean VC between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.853295% CI: [-15.19, 18.14]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean VC between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.775295% CI: [-14, 18.44]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean VC between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.517495% CI: [-12.7, 24.18]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean VC between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.639395% CI: [-12.61, 19.94]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean VC between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.536195% CI: [-12.28, 22.73]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean VC between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.815995% CI: [-13.26, 16.6]t-test, 2 sided
Secondary
Between-Group Difference in Mean White Blood Cell (WBC) Counts
Analysis 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.
Time frame: 30 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | Pre-WLL (Month -1) | 7.7 x10^6 cells/ml | Standard Deviation 1.8 |
| Control Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 6 months | 6.8 x10^6 cells/ml | Standard Deviation 1.6 |
| Control Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 1 month | 6.8 x10^6 cells/ml | Standard Deviation 1.6 |
| Control Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 10 months | 67 x10^6 cells/ml | Standard Deviation 1.8 |
| Control Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | Baseline (Month 0) | 7.5 x10^6 cells/ml | Standard Deviation 1.7 |
| Control Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 18 months | 6.8 x10^6 cells/ml | Standard Deviation 1.6 |
| Control Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 3 months | 6.8 x10^6 cells/ml | Standard Deviation 1.4 |
| Control Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 30 months | 6.8 x10^6 cells/ml | Standard Deviation 1.6 |
| GM-CSF Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 3 months | 5.9 x10^6 cells/ml | Standard Deviation 1.1 |
| GM-CSF Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 30 months | 6.1 x10^6 cells/ml | Standard Deviation 1.5 |
| GM-CSF Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | Baseline (Month 0) | 8.7 x10^6 cells/ml | Standard Deviation 2.7 |
| GM-CSF Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 1 month | 6.4 x10^6 cells/ml | Standard Deviation 1.6 |
| GM-CSF Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | Pre-WLL (Month -1) | 6.2 x10^6 cells/ml | Standard Deviation 1.2 |
| GM-CSF Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 6 months | 6.2 x10^6 cells/ml | Standard Deviation 1.3 |
| GM-CSF Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 10 months | 6.1 x10^6 cells/ml | Standard Deviation 1.1 |
| GM-CSF Group | Between-Group Difference in Mean White Blood Cell (WBC) Counts | 18 months | 6.5 x10^6 cells/ml | Standard Deviation 10 |
Comparison: The secondary analysis includes evaluation of the difference in mean WBC counts between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.058295% CI: [-3.17, 0.06]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean WBC counts between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.306895% CI: [-1.17, 3.48]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean WBC counts between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.564795% CI: [-2.04, 1.15]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean WBC counts between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.166995% CI: [-2.11, 0.4]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean WBC counts between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.45395% CI: [-1.99, 0.93]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean WBC counts between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.459495% CI: [-2.04, 0.97]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean WBC counts between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.630295% CI: [-1.61, 1]t-test, 2 sided
Comparison: The secondary analysis includes evaluation of the difference in mean WBC counts between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.3395% CI: [-2.24, 0.8]t-test, 2 sided
Secondary
Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels
Primary 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).
Time frame: 30 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | Pre-WLL (Month -1) | 18 ng/ml |
| Control Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | Baseline (Month 0) | 8 ng/ml |
| Control Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 1 month | 6 ng/ml |
| Control Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 3 months | 8 ng/ml |
| Control Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 6 months | 10 ng/ml |
| Control Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 10 months | 9 ng/ml |
| Control Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 18 months | 9 ng/ml |
| Control Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 30 months | 8 ng/ml |
| GM-CSF Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 30 months | 5 ng/ml |
| GM-CSF Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 1 month | 3 ng/ml |
| GM-CSF Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | Pre-WLL (Month -1) | 6 ng/ml |
| GM-CSF Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 6 months | 3 ng/ml |
| GM-CSF Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | Baseline (Month 0) | 5 ng/ml |
| GM-CSF Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 18 months | 3 ng/ml |
| GM-CSF Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 10 months | 2 ng/ml |
| GM-CSF Group | Between-Group Difference in Median Serum Carcinoembryonic Antigen (CEA) Levels | 3 months | 4 ng/ml |
Comparison: Primary Analysisp-value: 0.00195% CI: [-0.71, -0.22]Repeated measures ANOVA
Comparison: The secondary analysis includes evaluation of the difference in median serum CEA levels between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.0059Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum CEA levels between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.0382Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum CEA levels between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.077Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum CEA levels between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.04Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum CEA levels between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.0142Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum CEA levels between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.0071Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum CEA levels between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.0137Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum CEA levels between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.0315Wilcoxon (Mann-Whitney)
Secondary
Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels
Analysis 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).
Time frame: 30 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 1 month | 25 mcg/ml |
| Control Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 6 months | 22 mcg/ml |
| Control Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | Baseline (Month 0) | 20 mcg/ml |
| Control Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 10 months | 22 mcg/ml |
| Control Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 18 months | 19 mcg/ml |
| Control Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 3 months | 27 mcg/ml |
| Control Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 30 months | 19 mcg/ml |
| Control Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | Pre-WLL (Month -1) | 23 mcg/ml |
| GM-CSF Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 30 months | 12 mcg/ml |
| GM-CSF Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 10 months | 33 mcg/ml |
| GM-CSF Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | Pre-WLL (Month -1) | 32 mcg/ml |
| GM-CSF Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | Baseline (Month 0) | 28 mcg/ml |
| GM-CSF Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 1 month | 30 mcg/ml |
| GM-CSF Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 3 months | 34 mcg/ml |
| GM-CSF Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 6 months | 36 mcg/ml |
| GM-CSF Group | Between-Group Difference in Median Serum GM-CSF Autoantibody (GMAb) Levels | 18 months | 24 mcg/ml |
Comparison: The secondary analysis includes evaluation of the difference in median serum GMAb levels between groups at the Pre-WLL visit after imputation of missing data using a last observation carried forward method.p-value: 0.3865Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum GMAb levels between groups at the baseline visit after imputation of missing data using a last observation carried forward method.p-value: 0.1672Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum GMAb levels between groups at the 1-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.4363Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum GMAb levels between groups at the 3-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.1615Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum GMAb levels between groups at the 6-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.1615Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum GMAb levels between groups at the 10-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.3865Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum GMAb levels between groups at the 18-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.6475Wilcoxon (Mann-Whitney)
Comparison: The secondary analysis includes evaluation of the difference in median serum GMAb levels between groups at the 30-month visit after imputation of missing data using a last observation carried forward method.p-value: 0.6481Wilcoxon (Mann-Whitney)
Secondary
Number of Patients Requiring a Rescue WLL
Number of patients requiring an unscheduled rescue WLL during the 30-months immediately following administration of the scheduled baseline WLL therapy at Study Month 0.
Time frame: 30 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Group | Number of Patients Requiring a Rescue WLL | 7 participants |
| GM-CSF Group | Number of Patients Requiring a Rescue WLL | 1 participants |
p-value: 0.015295% CI: [1.6, 39.9]Fisher Exact