IMPALA: Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis
Study Details
Study Description
Brief Summary
This study evaluates inhaled molgramostim (recombinant human granulocyte macrophage-colony stimulating factor [rhGM-CSF]) in the treatment of autoimmune pulmonary alveolar proteinosis (aPAP) patients. A third of the patients will receive inhaled molgramostim once daily for 24 weeks, a third will receive inhaled molgramostim intermittently (7 days on, 7 days off) for 24 weeks and a third will receive inhaled matching placebo for 24 weeks.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
The trial is a phase 2, randomized, double-blind, placebo-controlled multicentre clinical trial investigating efficacy and safety of inhaled molgramostim (rhGM-CSF) in patients with aPAP.
The trial will include 2 periods; a double-blind treatment period consisting of up to 8 trial visits (Screening, Baseline, and at Weeks 4, 8,12, 16, 20 and 24 after randomisation) and a open-label follow-up period consisting of up to 5 trial visits (at Weeks 4, 12, 24, 36 and 48 post-treatment).
In the double-blind treatment period, eligible subjects will be randomised to treatment for up to 24 weeks with either: 1) inhaled molgramostim (300 µg) once daily (MOL-OD), 2) inhaled molgramostim (300 µg) and matching placebo administered intermittently (7 days on and 7 days off) (MOL-INT) or 3) inhaled placebo once daily (PBO). During the follow-up period, all participants will receive inhaled molgramostim intermittently (7 days on, 7 days off). During the trial, whole lung lavage (WLL) may be applied as rescue therapy in case of significant clinical worsening.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Double-blind molgramostim once daily Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks |
Drug: Molgramostim
300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation
Other Names:
Device: PARI eFlow nebulizer system
PARI eFlow nebulizer system
|
Experimental: Double-blind molgramostim intermittent Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) |
Drug: Molgramostim
300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation
Other Names:
Device: PARI eFlow nebulizer system
PARI eFlow nebulizer system
|
Placebo Comparator: Double-blind placebo Inhalation of placebo nebuliser solution once daily for 24 weeks |
Drug: Placebo
Placebo nebulizer solution for inhalation
Device: PARI eFlow nebulizer system
PARI eFlow nebulizer system
|
Experimental: Open-label molgramostim intermittent Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 or 48 weeks from completion of the double-blind period |
Drug: Molgramostim
300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation
Other Names:
Device: PARI eFlow nebulizer system
PARI eFlow nebulizer system
|
Outcome Measures
Primary Outcome Measures
- Absolute Change From Baseline of Alveolar-arterial Oxygen Concentration (A-a(DO2)) After 24 Weeks of Treatment [From baseline to 24 weeks]
Measurement of (A-a)DO2 was done by blood gas analysis. An arterial blood sample was collected in the supine position, after resting for at least 10 minutes (or longer if required to achieve stable oxygen saturation). The sample was analyzed for arterial oxygen tension (PaO2) and partial pressure of carbon dioxide (PaCO2). The calculation of (A-a)DO2 was done centrally by using a formula described in the protocol.
Secondary Outcome Measures
- Change From Baseline in 6-minute Walking Distance (6MWD) After 24 Weeks of Treatment [From baseline to 24 weeks]
The 6MWD was assessed by the use of 6-minute walking test (6MWT). The 6MWT was performed in accordance with the 2014 ATS/ERS guideline "field walking tests in chronic respiratory disease" (Holland et al. 2014) by technicians with documented training and experience. Where possible, the test was conducted with the participant breathing ambient atmospheric air. If the participant required oxygen supplementation at rest, a titration procedure was carried out as part of the 6MWT at screening in order to determine the oxygen flow rate required for the participant to complete the test. This flow rate was to be used during subsequent tests, if possible.
- Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score After 24 Weeks of Treatment [From baseline to 24 weeks]
The SGRQ is designed to measure health impairment in patients with asthma and chronic obstructive pulmonary disease (COPD). It consists of two parts, where Part 1 covers the participants' recollection of their symptoms over the preceding period (1 month recall used in this trial, Symptoms component) and Part 2 addresses the participants' current state in terms of disturbances to their daily physical activity (Activity component) and a wide range of disturbances of psycho-social function (Impact component). A total score as well as individual component scores were calculated. Scores (total and component) range from 0 to 100, with higher scores indicating more limitations.
- Number of Whole Lung Lavage During 24 Weeks of Treatment [From baseline to 24 weeks]
In all versions of the protocol (no participants were recruited under version 1.0), whole lung lavage (single lung or both lungs) was applied as rescue therapy. In protocol version 2.0, the criterion for performing whole lung lavage was an increase in (A-a)DO2 by more than 10 mmHg/1.33 kilopascal compared to baseline. In protocol version 3.0 onwards, the criterion for performing whole lung lavage was clinical worsening of aPAP based on symptoms, reduced exercise capacity and/or findings of hypoxemia or desaturation according to the investigator's judgement. In protocol versions 2.0 and 3.0, participants undergoing whole lung lavage during the double-blind period were to discontinue double-blind treatment, encouraged to continue to follow the same visit schedule and, if required, receive further whole lung lavage at the investigator's discretion. In protocol version 4.0 and 5.0, participants undergoing whole lung lavage were to continue double-blind treatment.
- Number of Adverse Events (AEs) During 24 Weeks of Treatment [From baseline to 24 weeks]
Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. Information about AEs was collected by the investigator by a non-leading question such as "have you experienced any new health problems or worsening of existing conditions" and by reporting events directly observed or spontaneously volunteered by participants (e.g., in the Subject Diary Card, where subjects were asked to record any AEs and answer questions regarding lung toxicity and known systemic effects). Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns. All AEs were assessed by the investigator for severity (mild, moderate, severe), outcome (recovered, not recovered, recovered with sequelae, fatal, unknown) and causality (unlikely, possible, probable, not applicable) according to current regulatory standards.
- Number of Serious Adverse Events (SAEs) During 24 Weeks of Treatment [From baseline to 24 weeks]
SAEs are defined as any untoward medicinal occurrence or effect that at any dose: Results in death Is life-threatening Requires hospitalisation or prolongation of existing hospitalisation Results in persistent or significant disability or incapacity Is a congenital anomaly or birth defect May jeopardise the subject or may require intervention to prevent one or more of the other outcomes listed above (Important Medical Events)
- Number of Adverse Drug Reactions (ADRs) During 24 Weeks of Treatment [From baseline to 24 weeks]
All AEs judged by either the reporting investigator or the sponsor as having a reasonable causal relationship to a medicinal product qualify as ADRs. The expression reasonable causal relationship means that a causal relationship between a medicinal product and an AE is at least a reasonable possibility i.e. the relationship cannot be ruled out.
- Number of Severe AEs During 24 Weeks of Treatment [From baseline to 24 weeks]
All AEs were assessed by the investigator for severity (mild, moderate, severe) according to current regulatory standards: Mild: The AE is easily tolerated and does not interfere with daily activity. Moderate: The AE interferes with daily activity, but the subject is still able to function. Medical intervention may be considered. Severe: The AE is incapacitating and requires medical intervention.
- Number of Participants With at Least 1 AE Leading to Treatment Discontinuation During 24 Weeks of Treatment [From baseline to 24 weeks]
Participants could be discontinued from treatment and assessments at any time, if deemed necessary by the investigator. Potential reasons for discontinuation of treatment included e.g. unacceptable AE.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
aPAP diagnosed by computed tomography, or by biopsy, or by Broncho Alveolar Lavage (BAL), and by increased GM-CSF autoantibodies in serum.
-
Stable or progressive aPAP during a minimum period of 2 months prior to the Baseline visit.
-
Arterial oxygen tension (PaO2) <75 mmHg/<10 kilo Pascal (kPa) at rest, OR desaturation of >4 percentage points on the 6MWT
-
An alveolar-arterial oxygen difference [(A-a)DO2] of minimum 25 mmHg/3.33 kPa
-
Female or male ≥18 years of age
-
Females who have been post-menopausal for >1 year or females of childbearing potential after a confirmed menstrual period using a highly efficient method of contraception (i.e. a method with <1% failure rate such as combined hormonal contraception, progesterone-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence), during and until 30 days after last dose of double-blind trial treatment. Females of childbearing potential must have a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at dosing at Baseline (Visit
- and must not be lactating
-
Males agreeing to use condoms during and until 30 days after last dose of double-blind medication, or males having a female partner who is using adequate contraception as described above
-
Willing and able to provide signed informed consent
-
Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures specified in the protocol as judged by the investigator
Exclusion Criteria:
-
Diagnosis of hereditary or secondary PAP
-
WLL within 1 month of Baseline
-
Treatment with GM-CSF within 3 months of Baseline
-
Treatment with rituximab within 6 months of Baseline
-
Treatment with plasmapheresis within 3 months of Baseline
-
Treatment with any investigational medicinal product within 4 weeks of Screening
-
Concomitant use of sputum modifying drugs such as carbocysteine or ambroxol
-
History of allergic reactions to GM-CSF
-
Connective tissue disease, inflammatory bowel disease or other autoimmune disorder requiring treatment associated with significant immunosuppression, e.g. more than 10 mg/day systemic prednisolone
-
Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product
-
History of, or present, myeloproliferative disease or leukaemia
-
Known active infection (viral, bacterial, fungal or mycobacterial)
-
Apparent pre-existing concurrent pulmonary fibrosis
-
Any other serious medical condition which in the opinion of the investigator would make the participant unsuitable for the trial
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | UCLA | Los Angeles | California | United States | 90095 |
2 | University of Florida | Gainesville | Florida | United States | 32610 |
3 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
4 | Royal Prince Alfred Hospital | Sydney | New South Wales | Australia | 2050 |
5 | Aarhus University Hospital | Aarhus | Denmark | ||
6 | CHU Rennes Hospital Pontchaillou | Rennes | France | ||
7 | Westdeutsches Lungenzentrum am Universitätsklinikum Essen | Essen | Germany | ||
8 | Asklepios Fachkliniken München - Gauting | Gauting | Germany | 82131 | |
9 | Thoraxklinik am Universitätsklinikum Heidelberg | Heidelberg | Germany | ||
10 | Universitätsklinikum Schleswig-Holstein Zentralklinikum, Lübeck Medizinische Klinik III, Pneumologie | Lübeck | Germany | 23538 | |
11 | Attikon University Hospital | Athens | Greece | ||
12 | Rabin Medical Center | Petaẖ Tiqwa | Israel | ||
13 | IRCCS Policlinico San Matteo | Pavia | Italy | ||
14 | Niigata University Medical and Dental Hospital | Niigata | Japan | ||
15 | National Hospital Organization Kinki-Chuo | Osaka | Japan | ||
16 | Tohoku University Hospital | Sendai | Japan | ||
17 | Aichi Medical University Hospital | Toyohashi | Japan | ||
18 | Kanagawa Cardiovascular and Respiratory Center | Yokohama | Japan | ||
19 | Seoul National University Hospital | Seoul | Korea, Republic of | 0 3080 | |
20 | Asan Medical Center, Division of Pulmonary and Critical Care Medicine | Seoul | Korea, Republic of | 05505 | |
21 | Samsung Medical Center, Division of Pulmonary and Critical Care Medicine | Seoul | Korea, Republic of | 135-710 | |
22 | St. Antonius Hospital | Nieuwegein | Netherlands | ||
23 | Hospital de dia de Pneumologia | Lisboa | Portugal | ||
24 | Hospital Sao Joao | Porto | Portugal | 4200-319 | |
25 | City Hospital St. Petersburg | St. Petersburg | Russian Federation | ||
26 | II. Pulmonary Department National Institut for TB, Lung Diseases and Chest Surgery | Vyšné Hágy | Slovakia | 05984 | |
27 | Hospital University de Bellvitge (HUB) | Barcelona | Spain | 08907 | |
28 | Centre Hospitalier Universitaire Vaudois | Lausanne | Switzerland | ||
29 | Yedikule Pulmonary Diseases and Pulmonary Surgery Training and Research Hospital | İstanbul | Turkey | 34020 | |
30 | Royal Brompton Hospital | London | United Kingdom |
Sponsors and Collaborators
- Savara Inc.
Investigators
- Principal Investigator: Cliff Morgan, MD, Royal Brompton Hospital London
Study Documents (Full-Text)
More Information
Publications
- MOL-PAP-002
- 2015-003878-33
Study Results
Participant Flow
Recruitment Details | 30 sites in 18 countries (United Kingdom, Denmark, Germany, Italy, France, Greece, Switzerland, Spain, Portugal, Slovakia, Netherlands, Turkey, Russia, Israel, Japan, South Korea, Australia, and the US) enrolled participants in the trial. First participant was enrolled on 21 March 2016 and last subject completed the study on 27 September 2019. |
---|---|
Pre-assignment Detail | A total of 235 participants were screened, and 138 were randomized and treated. 1 participant in the MOL-INT group and 1 participant in the PBO group withdrew between the double-blind period and the open-label period. 1 participant who withdrew from the double-blind period entered the open-label period. |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Period Title: Double-blind Treatment Period | |||
STARTED | 46 | 45 | 47 |
COMPLETED | 45 | 44 | 43 |
NOT COMPLETED | 1 | 1 | 4 |
Period Title: Double-blind Treatment Period | |||
STARTED | 45 | 43 | 43 |
COMPLETED | 45 | 42 | 41 |
NOT COMPLETED | 0 | 1 | 2 |
Baseline Characteristics
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo | Total |
---|---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Total of all reporting groups |
Overall Participants | 46 | 45 | 47 | 138 |
Age (Count of Participants) | ||||
<=18 years |
0
0%
|
1
2.2%
|
0
0%
|
1
0.7%
|
Between 18 and 65 years |
34
73.9%
|
37
82.2%
|
41
87.2%
|
112
81.2%
|
>=65 years |
12
26.1%
|
7
15.6%
|
6
12.8%
|
25
18.1%
|
Age (years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [years] |
54.0
(13.32)
|
49.2
(14.06)
|
46.1
(14.84)
|
49.8
(14.36)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
18
39.1%
|
19
42.2%
|
22
46.8%
|
59
42.8%
|
Male |
28
60.9%
|
26
57.8%
|
25
53.2%
|
79
57.2%
|
Race (NIH/OMB) (Count of Participants) | ||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
25
54.3%
|
13
28.9%
|
11
23.4%
|
49
35.5%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
1
2.2%
|
0
0%
|
0
0%
|
1
0.7%
|
White |
20
43.5%
|
32
71.1%
|
36
76.6%
|
88
63.8%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | ||||
United States |
2
4.3%
|
2
4.4%
|
0
0%
|
4
2.9%
|
Japan |
20
43.5%
|
10
22.2%
|
10
21.3%
|
40
29%
|
United Kingdom |
1
2.2%
|
3
6.7%
|
1
2.1%
|
5
3.6%
|
Switzerland |
0
0%
|
0
0%
|
1
2.1%
|
1
0.7%
|
Portugal |
0
0%
|
1
2.2%
|
2
4.3%
|
3
2.2%
|
Russia |
1
2.2%
|
1
2.2%
|
6
12.8%
|
8
5.8%
|
Spain |
0
0%
|
1
2.2%
|
1
2.1%
|
2
1.4%
|
Greece |
1
2.2%
|
0
0%
|
3
6.4%
|
4
2.9%
|
Netherlands |
2
4.3%
|
3
6.7%
|
1
2.1%
|
6
4.3%
|
South Korea |
3
6.5%
|
2
4.4%
|
1
2.1%
|
6
4.3%
|
Turkey |
4
8.7%
|
4
8.9%
|
2
4.3%
|
10
7.2%
|
Denmark |
1
2.2%
|
1
2.2%
|
1
2.1%
|
3
2.2%
|
Italy |
3
6.5%
|
3
6.7%
|
7
14.9%
|
13
9.4%
|
Israel |
1
2.2%
|
5
11.1%
|
1
2.1%
|
7
5.1%
|
Slovakia |
2
4.3%
|
1
2.2%
|
1
2.1%
|
4
2.9%
|
France |
2
4.3%
|
1
2.2%
|
2
4.3%
|
5
3.6%
|
Australia |
0
0%
|
1
2.2%
|
0
0%
|
1
0.7%
|
Germany |
3
6.5%
|
6
13.3%
|
7
14.9%
|
16
11.6%
|
Smoking (Count of Participants) | ||||
Previous |
27
58.7%
|
20
44.4%
|
20
42.6%
|
67
48.6%
|
Never |
13
28.3%
|
16
35.6%
|
16
34%
|
45
32.6%
|
Current |
6
13%
|
9
20%
|
11
23.4%
|
26
18.8%
|
Time since aPAP diagnosis (months) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [months] |
39.8
(58.12)
|
40.0
(45.87)
|
32.0
(31.50)
|
37.2
(46.18)
|
Participants with previous whole lung lavage (Count of Participants) | ||||
Count of Participants [Participants] |
23
50%
|
31
68.9%
|
30
63.8%
|
84
60.9%
|
Disease severity score (DSS) (Count of Participants) | ||||
DSS 1: No symptoms and PaO2 ≥70 mmHg |
4
8.7%
|
5
11.1%
|
3
6.4%
|
12
8.7%
|
DSS 2: Symptomatic and PaO2 ≥70 mmHg |
12
26.1%
|
14
31.1%
|
16
34%
|
42
30.4%
|
DSS 3: 60 mmHg ≤ PaO2 <70 mmHg |
17
37%
|
13
28.9%
|
14
29.8%
|
44
31.9%
|
DSS 4: 50 mm Hg ≤ PaO2 <60 mmHg |
5
10.9%
|
9
20%
|
10
21.3%
|
24
17.4%
|
DSS 5: PaO2 <50 mmHg |
8
17.4%
|
4
8.9%
|
4
8.5%
|
16
11.6%
|
Outcome Measures
Title | Absolute Change From Baseline of Alveolar-arterial Oxygen Concentration (A-a(DO2)) After 24 Weeks of Treatment |
---|---|
Description | Measurement of (A-a)DO2 was done by blood gas analysis. An arterial blood sample was collected in the supine position, after resting for at least 10 minutes (or longer if required to achieve stable oxygen saturation). The sample was analyzed for arterial oxygen tension (PaO2) and partial pressure of carbon dioxide (PaCO2). The calculation of (A-a)DO2 was done centrally by using a formula described in the protocol. |
Time Frame | From baseline to 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set (FAS): all randomized participants, analyzed according to randomized treatment. Not all participants in the FAS had blood gas analysis done at Week 24, therefore the overall number of participants analyzed is less than the total number of randomized participants. |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Measure Participants | 45 | 43 | 43 |
Mean (Standard Deviation) [mmHg] |
28.6
(21.95)
|
29.3
(17.96)
|
32.0
(20.90)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Molgramostim Once Daily, Placebo |
---|---|---|
Comments | Primary endpoint was evaluated using analysis of covariance with treatment, whole lung lavage within 2 months before baseline, and geographic region as factors, and baseline values as covariates. To control type I error, key secondary endpoints were analyzed using a testing hierarchy wherein once daily molgramostim and placebo was compared and if statistical significance was reached, evaluation of intermittent molgramostim and placebo would proceed. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1688 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least Square Means (LSmean) |
Estimated Value | -4.6 | |
Confidence Interval |
(2-Sided) 95% -11.1 to 2.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The estimated value represents the estimated difference between once daily molgramostim and placebo groups in LSmean change from baseline to week 24. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Molgramostim Intermittent, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3968 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least Square Means (LSmean) |
Estimated Value | -2.8 | |
Confidence Interval |
(2-Sided) 95% -9.3 to 3.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The estimated value represents the estimated difference between intermittent molgramostim and placebo groups in LSmean change from baseline to week 24. |
Title | Change From Baseline in 6-minute Walking Distance (6MWD) After 24 Weeks of Treatment |
---|---|
Description | The 6MWD was assessed by the use of 6-minute walking test (6MWT). The 6MWT was performed in accordance with the 2014 ATS/ERS guideline "field walking tests in chronic respiratory disease" (Holland et al. 2014) by technicians with documented training and experience. Where possible, the test was conducted with the participant breathing ambient atmospheric air. If the participant required oxygen supplementation at rest, a titration procedure was carried out as part of the 6MWT at screening in order to determine the oxygen flow rate required for the participant to complete the test. This flow rate was to be used during subsequent tests, if possible. |
Time Frame | From baseline to 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
FAS. Not all participants in the FAS had 6MWT done at Week 24, therefore the overall number of participants analyzed is less than the total number of randomized participants. |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Measure Participants | 43 | 43 | 43 |
Mean (Standard Deviation) [meters] |
39.6
(95.89)
|
11.3
(81.94)
|
6.0
(97.17)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Molgramostim Once Daily, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3159 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least Square Means (LSmean) |
Estimated Value | 20.6 | |
Confidence Interval |
(2-Sided) 95% -19.8 to 61.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The estimated value represents the estimated difference between once daily molgramostim and placebo groups in LSmean change from baseline to week 24. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Molgramostim Intermittent, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.7809 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least Square Means (LSmean) |
Estimated Value | 5.6 | |
Confidence Interval |
(2-Sided) 95% -34.1 to 45.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The estimated value represents the estimated difference between intermittent molgramostim and placebo groups in LSmean change from baseline to week 24. |
Title | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score After 24 Weeks of Treatment |
---|---|
Description | The SGRQ is designed to measure health impairment in patients with asthma and chronic obstructive pulmonary disease (COPD). It consists of two parts, where Part 1 covers the participants' recollection of their symptoms over the preceding period (1 month recall used in this trial, Symptoms component) and Part 2 addresses the participants' current state in terms of disturbances to their daily physical activity (Activity component) and a wide range of disturbances of psycho-social function (Impact component). A total score as well as individual component scores were calculated. Scores (total and component) range from 0 to 100, with higher scores indicating more limitations. |
Time Frame | From baseline to 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
FAS. Not all participants in the FAS had SGRQ assessed at Week 24, therefore the overall number of participants analyzed is less than the total number of randomized participants. |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Measure Participants | 45 | 44 | 43 |
Mean (Standard Deviation) [score on a scale] |
-12.3
(14.30)
|
-12.0
(15.12)
|
-4.7
(12.83)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Molgramostim Once Daily, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0103 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least Square Means (LSmean) |
Estimated Value | -7.6 | |
Confidence Interval |
(2-Sided) 95% -13.4 to -1.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The estimated value represents the estimated difference between once daily molgramostim and placebo groups in LSmean change from baseline to week 24. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Molgramostim Intermittent, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0173 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least Square Means (LSmean) |
Estimated Value | -7.0 | |
Confidence Interval |
(2-Sided) 95% -12.7 to -1.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The estimated value represents the estimated difference between intermittent molgramostim and placebo groups in LSmean change from baseline to week 24.. |
Title | Number of Whole Lung Lavage During 24 Weeks of Treatment |
---|---|
Description | In all versions of the protocol (no participants were recruited under version 1.0), whole lung lavage (single lung or both lungs) was applied as rescue therapy. In protocol version 2.0, the criterion for performing whole lung lavage was an increase in (A-a)DO2 by more than 10 mmHg/1.33 kilopascal compared to baseline. In protocol version 3.0 onwards, the criterion for performing whole lung lavage was clinical worsening of aPAP based on symptoms, reduced exercise capacity and/or findings of hypoxemia or desaturation according to the investigator's judgement. In protocol versions 2.0 and 3.0, participants undergoing whole lung lavage during the double-blind period were to discontinue double-blind treatment, encouraged to continue to follow the same visit schedule and, if required, receive further whole lung lavage at the investigator's discretion. In protocol version 4.0 and 5.0, participants undergoing whole lung lavage were to continue double-blind treatment. |
Time Frame | From baseline to 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
FAS. |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Measure Participants | 46 | 45 | 47 |
Number [lavages] |
9
|
7
|
17
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Molgramostim Once Daily, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1918 |
Comments | ||
Method | Negative binomial regression | |
Comments | ||
Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
Estimated Value | 0.284 | |
Confidence Interval |
(2-Sided) 95% 0.043 to 1.881 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The estimated value represents the RR between once daily molgramostim and placebo groups. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Molgramostim Intermittent, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2421 |
Comments | ||
Method | Negative binomial regression | |
Comments | ||
Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
Estimated Value | 0.367 | |
Confidence Interval |
(2-Sided) 95% 0.068 to 1.968 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The estimated value represents the RR between intermittent molgramostim and placebo groups. |
Title | Number of Adverse Events (AEs) During 24 Weeks of Treatment |
---|---|
Description | Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. Information about AEs was collected by the investigator by a non-leading question such as "have you experienced any new health problems or worsening of existing conditions" and by reporting events directly observed or spontaneously volunteered by participants (e.g., in the Subject Diary Card, where subjects were asked to record any AEs and answer questions regarding lung toxicity and known systemic effects). Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns. All AEs were assessed by the investigator for severity (mild, moderate, severe), outcome (recovered, not recovered, recovered with sequelae, fatal, unknown) and causality (unlikely, possible, probable, not applicable) according to current regulatory standards. |
Time Frame | From baseline to 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Safety analysis set: all randomized participants who received at least one dose of the trial drug, analyzed according to actual treatment. |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Measure Participants | 46 | 45 | 47 |
Number [events] |
215
|
191
|
192
|
Title | Number of Serious Adverse Events (SAEs) During 24 Weeks of Treatment |
---|---|
Description | SAEs are defined as any untoward medicinal occurrence or effect that at any dose: Results in death Is life-threatening Requires hospitalisation or prolongation of existing hospitalisation Results in persistent or significant disability or incapacity Is a congenital anomaly or birth defect May jeopardise the subject or may require intervention to prevent one or more of the other outcomes listed above (Important Medical Events) |
Time Frame | From baseline to 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Safety analysis set |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Measure Participants | 46 | 45 | 47 |
Number [events] |
13
|
5
|
16
|
Title | Number of Adverse Drug Reactions (ADRs) During 24 Weeks of Treatment |
---|---|
Description | All AEs judged by either the reporting investigator or the sponsor as having a reasonable causal relationship to a medicinal product qualify as ADRs. The expression reasonable causal relationship means that a causal relationship between a medicinal product and an AE is at least a reasonable possibility i.e. the relationship cannot be ruled out. |
Time Frame | From baseline to 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Safety analysis set |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Measure Participants | 46 | 45 | 47 |
Number [events] |
53
|
27
|
33
|
Title | Number of Severe AEs During 24 Weeks of Treatment |
---|---|
Description | All AEs were assessed by the investigator for severity (mild, moderate, severe) according to current regulatory standards: Mild: The AE is easily tolerated and does not interfere with daily activity. Moderate: The AE interferes with daily activity, but the subject is still able to function. Medical intervention may be considered. Severe: The AE is incapacitating and requires medical intervention. |
Time Frame | From baseline to 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Safety analysis set |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Measure Participants | 46 | 45 | 47 |
Number [events] |
28
|
11
|
38
|
Title | Number of Participants With at Least 1 AE Leading to Treatment Discontinuation During 24 Weeks of Treatment |
---|---|
Description | Participants could be discontinued from treatment and assessments at any time, if deemed necessary by the investigator. Potential reasons for discontinuation of treatment included e.g. unacceptable AE. |
Time Frame | From baseline to 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Safety analysis set |
Arm/Group Title | Molgramostim Once Daily | Molgramostim Intermittent | Placebo |
---|---|---|---|
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system |
Measure Participants | 46 | 45 | 47 |
Count of Participants [Participants] |
2
4.3%
|
1
2.2%
|
1
2.1%
|
Adverse Events
Time Frame | Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Information about AEs was collected by the investigator by a non-leading question such as "have you experienced any new health problems or worsening of existing conditions" and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns. | |||||||
Arm/Group Title | Double-blind Molgramostim Once Daily | Double-blind Molgramostim Intermittent | Double-blind Placebo | Open-label Molgramostim Intermittent | ||||
Arm/Group Description | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of placebo nebuliser solution once daily for 24 weeks Placebo: Placebo nebulizer solution for inhalation PARI eFlow nebulizer system: PARI eFlow nebulizer system | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 or 48 weeks from completion of the double-blind period Molgramostim: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation | ||||
All Cause Mortality |
||||||||
Double-blind Molgramostim Once Daily | Double-blind Molgramostim Intermittent | Double-blind Placebo | Open-label Molgramostim Intermittent | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/46 (0%) | 0/45 (0%) | 0/47 (0%) | 0/130 (0%) | ||||
Serious Adverse Events |
||||||||
Double-blind Molgramostim Once Daily | Double-blind Molgramostim Intermittent | Double-blind Placebo | Open-label Molgramostim Intermittent | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 8/46 (17.4%) | 5/45 (11.1%) | 8/47 (17%) | 16/130 (12.3%) | ||||
Eye disorders | ||||||||
Cataract | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Hepatobiliary disorders | ||||||||
Cholelithiasis | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Infections and infestations | ||||||||
Pneumonia bacterial | 1/46 (2.2%) | 1 | 1/45 (2.2%) | 1 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Diverticulitis | 0/46 (0%) | 0 | 1/45 (2.2%) | 1 | 0/47 (0%) | 0 | 0/130 (0%) | 0 |
Lower respiratory tract infection | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 1/47 (2.1%) | 1 | 0/130 (0%) | 0 |
Pneumonia | 1/46 (2.2%) | 1 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 2/130 (1.5%) | 2 |
Respiratory tract infection | 1/46 (2.2%) | 1 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 0/130 (0%) | 0 |
Oesophageal candidiasis | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Oral candidiasis | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Influenza | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Bronchitis | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Urinary tract infection | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Lung infection | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Nasopharyngitis | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Investigations | ||||||||
Weight decreased | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Breast cancer | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Squamous cell carcinoma of the tongue | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Nervous system disorders | ||||||||
Aphasia | 1/46 (2.2%) | 1 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 0/130 (0%) | 0 |
Epilepsy | 1/46 (2.2%) | 1 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 0/130 (0%) | 0 |
Psychiatric disorders | ||||||||
Gambling disorder | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 1/47 (2.1%) | 1 | 0/130 (0%) | 0 |
Reproductive system and breast disorders | ||||||||
Prostatitis | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 1/130 (0.8%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||||||
Alveolar proteinosis | 3/46 (6.5%) | 4 | 3/45 (6.7%) | 3 | 6/47 (12.8%) | 12 | 6/130 (4.6%) | 7 |
Asthma | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 1/47 (2.1%) | 1 | 0/130 (0%) | 0 |
Cough | 1/46 (2.2%) | 1 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 0/130 (0%) | 0 |
Dyspnoea | 1/46 (2.2%) | 1 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 0/130 (0%) | 0 |
Laryngeal oedema | 1/46 (2.2%) | 1 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 0/130 (0%) | 0 |
Respiratory failure | 1/46 (2.2%) | 1 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 0/130 (0%) | 0 |
Surgical and medical procedures | ||||||||
Drug detoxification | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 1/47 (2.1%) | 1 | 0/130 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
Double-blind Molgramostim Once Daily | Double-blind Molgramostim Intermittent | Double-blind Placebo | Open-label Molgramostim Intermittent | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 39/46 (84.8%) | 41/45 (91.1%) | 41/47 (87.2%) | 87/130 (66.9%) | ||||
Gastrointestinal disorders | ||||||||
Diarrhoea | 0/46 (0%) | 0 | 6/45 (13.3%) | 6 | 3/47 (6.4%) | 3 | 3/130 (2.3%) | 3 |
General disorders | ||||||||
Chest pain | 10/46 (21.7%) | 11 | 2/45 (4.4%) | 2 | 1/47 (2.1%) | 2 | 3/130 (2.3%) | 3 |
Pyrexia | 2/46 (4.3%) | 2 | 3/45 (6.7%) | 3 | 3/47 (6.4%) | 4 | 4/130 (3.1%) | 6 |
Infections and infestations | ||||||||
Nasopharyngitis | 7/46 (15.2%) | 10 | 10/45 (22.2%) | 12 | 6/47 (12.8%) | 6 | 24/130 (18.5%) | 33 |
Respiratory tract infection | 2/46 (4.3%) | 2 | 2/45 (4.4%) | 2 | 2/47 (4.3%) | 2 | 4/130 (3.1%) | 4 |
Upper respiratory tract infection | 0/46 (0%) | 0 | 3/45 (6.7%) | 3 | 3/47 (6.4%) | 3 | 5/130 (3.8%) | 6 |
Investigations | ||||||||
Weight increased | 3/46 (6.5%) | 4 | 5/45 (11.1%) | 6 | 0/47 (0%) | 0 | 3/130 (2.3%) | 3 |
Musculoskeletal and connective tissue disorders | ||||||||
Back pain | 2/46 (4.3%) | 5 | 3/45 (6.7%) | 4 | 1/47 (2.1%) | 1 | 4/130 (3.1%) | 4 |
Arthralgia | 2/46 (4.3%) | 2 | 0/45 (0%) | 0 | 4/47 (8.5%) | 4 | 0/130 (0%) | 0 |
Nervous system disorders | ||||||||
Headache | 6/46 (13%) | 9 | 7/45 (15.6%) | 9 | 7/47 (14.9%) | 16 | 3/130 (2.3%) | 6 |
Dizziness | 2/46 (4.3%) | 2 | 2/45 (4.4%) | 2 | 2/47 (4.3%) | 4 | 3/130 (2.3%) | 4 |
Respiratory, thoracic and mediastinal disorders | ||||||||
Cough | 15/46 (32.6%) | 22 | 12/45 (26.7%) | 18 | 11/47 (23.4%) | 12 | 11/130 (8.5%) | 14 |
Dyspnoea | 5/46 (10.9%) | 8 | 7/45 (15.6%) | 7 | 4/47 (8.5%) | 5 | 4/130 (3.1%) | 8 |
Alveolar proteinosis | 3/46 (6.5%) | 4 | 5/45 (11.1%) | 5 | 8/47 (17%) | 18 | 7/130 (5.4%) | 10 |
Productive cough | 4/46 (8.7%) | 5 | 3/45 (6.7%) | 3 | 3/47 (6.4%) | 3 | 3/130 (2.3%) | 3 |
Skin and subcutaneous tissue disorders | ||||||||
Rash | 0/46 (0%) | 0 | 0/45 (0%) | 0 | 0/47 (0%) | 0 | 6/130 (4.6%) | 6 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dhaval Desai, VP Head of Clinical Development |
---|---|
Organization | Savara Inc |
Phone | +1 302-442-2309 |
dhaval.desai@savarapharma.com |
- MOL-PAP-002
- 2015-003878-33