Back to resultsSafety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis (IMPALA-X)
Primary Purpose
Autoimmune Pulmonary Alveolar Proteinosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Molgramostim
Sponsored by
About this trial
This is an interventional treatment trial for Autoimmune Pulmonary Alveolar Proteinosis
Eligibility Criteria
Inclusion Criteria:
- Completer of the IMPALA trial.
- Females who have been post menopausal for >1 year, or females of child-bearing potential who are not pregnant or lactating and are using acceptable contraceptive methods.
- Males agreeing to use using acceptable contraceptive methods.
- Willing and able to provide signed informed consent.
Exclusion Criteria:
- Treatment with GM-CSF products other than molgramostim nebuliser solution within three months of Baseline.
- Treatment with any investigational medicinal product other than inhaled molgramostim within four weeks of Baseline.
- 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.
- Apparent pre-existing concurrent pulmonary fibrosis.
- Any other serious medical condition which in the opinion of the investigator would make the subject unsuitable for the trial.
Sites / Locations
- Dept. Of Respiratory Diseases & Allergy
- CHU Rennes Hospital Pontchaillou, Service de Pneumologie
- Ruhrlandklinik Essen Westdeutsches Lungenzentrum am Universitätsklinikum Essen GmbH
- Asklepios Fachkliniken München - Gauting Klinik für Pneumologie
- Thoraxklinik am Universitätsklinikum Heidelberg Abteilung für Pneumologie und Beatmungsmedizin
- Universitätsklinikum Schleswig-Holstein Zentralklinikum Lübeck Medizinische Klinik III - Pneumologie
- Attikon University Hospital 2nd Pulmonary Department Athens Medical School National and Kapodistrian University of Athens
- Rabin Medical Center Institute of Pulomonary Medicine
- S.C. Pneumologia Fondazione IRCCS Policlinico San Matteo
- St. Antonius Hospital
- Pavlov first Saint Petersburg State Medical Univerisity
- Yedikule Pulmonary Diseases and Pulmonary Surgery Training and Research Hospital
- Dept. Of Intensive Care Unit Royal Brompton Hospital London
Outcomes
Primary Outcome Measures
Number of adverse events
Number of serious adverse events
Number of adverse drug reactions
Number of adverse events leading to treatment discontinuation
Secondary Outcome Measures
Alveolar-arterial oxygen gradient
Difference in oxygen tension between lungs and blood
6-minute walk distance
St Georges Respiratory Questionnaire total score
Respiratory-specific questionnaire measuring impact on overall health, daily life, and perceived well-being. Scores range from 0 to 100, with higher scores indicating more limitations.
Frequency of whole lung lavages during the trial
Diffusion capacity of the lung for carbon monoxide
Forced expiratory volume in one second
Forced vital capacity
Arterial oxygen tension
Pulmonary alveolar proteinosis Disease Severity Score
Disease-specific score graded based on symptoms of PAP and oxygenation of blood. Scores range from 1 to 5, where 5 indicates most severe disease.
Need for oxygen supplement therapy
Number of subjects not requiring treatment for pulmonary alveolar proteinosis
Time off treatment for pulmonary alveolar proteinosis
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03482752
Brief Title
Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis
Acronym
IMPALA-X
Official Title
An Open-label, Non-controlled, Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis Patients
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
April 16, 2018 (Actual)
Primary Completion Date
January 14, 2021 (Actual)
Study Completion Date
January 14, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Savara Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Clinical trial for subjects with autoimmune pulmonary alveolar proteinosis (aPAP) who have completed the IMPALA trial (NCT02702180).
At the Baseline visit, eligible subjects may continue or re-start treatment with 300 µg inhaled molgramostim (recombinant human Granulocyte-Macrophage Colony Stimulating Factor; GM-CSF) administered intermittently in cycles of seven days molgramostim, administered once daily, and seven days off treatment.
Subject will be treated with inhaled molgramostim for up to 36 months.
During the trial, whole lung lavage will be applied as rescue therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Pulmonary Alveolar Proteinosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Open Label, Non-controlled
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Molgramostim
Other Intervention Name(s)
Recombinant human GM-CSF
Intervention Description
300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Primary Outcome Measure Information:
Title
Number of adverse events
Time Frame
36 months
Title
Number of serious adverse events
Time Frame
36 months
Title
Number of adverse drug reactions
Time Frame
36 months
Title
Number of adverse events leading to treatment discontinuation
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Alveolar-arterial oxygen gradient
Description
Difference in oxygen tension between lungs and blood
Time Frame
36 months
Title
6-minute walk distance
Time Frame
36 months
Title
St Georges Respiratory Questionnaire total score
Description
Respiratory-specific questionnaire measuring impact on overall health, daily life, and perceived well-being. Scores range from 0 to 100, with higher scores indicating more limitations.
Time Frame
36 months
Title
Frequency of whole lung lavages during the trial
Time Frame
36 months
Title
Diffusion capacity of the lung for carbon monoxide
Time Frame
36 months
Title
Forced expiratory volume in one second
Time Frame
36 months
Title
Forced vital capacity
Time Frame
36 months
Title
Arterial oxygen tension
Time Frame
36 months
Title
Pulmonary alveolar proteinosis Disease Severity Score
Description
Disease-specific score graded based on symptoms of PAP and oxygenation of blood. Scores range from 1 to 5, where 5 indicates most severe disease.
Time Frame
36 months
Title
Need for oxygen supplement therapy
Time Frame
36 months
Title
Number of subjects not requiring treatment for pulmonary alveolar proteinosis
Time Frame
36 months
Title
Time off treatment for pulmonary alveolar proteinosis
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Completer of the IMPALA trial.
Females who have been post menopausal for >1 year, or females of child-bearing potential who are not pregnant or lactating and are using acceptable contraceptive methods.
Males agreeing to use using acceptable contraceptive methods.
Willing and able to provide signed informed consent.
Exclusion Criteria:
Treatment with GM-CSF products other than molgramostim nebuliser solution within three months of Baseline.
Treatment with any investigational medicinal product other than inhaled molgramostim within four weeks of Baseline.
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.
Apparent pre-existing concurrent pulmonary fibrosis.
Any other serious medical condition which in the opinion of the investigator would make the subject unsuitable for the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Bonella, Prof.
Organizational Affiliation
Interstitial and Rare Lung Disease Unit, Ruhrlandklinik University Hospital, Essen, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dept. Of Respiratory Diseases & Allergy
City
Århus
Country
Denmark
Facility Name
CHU Rennes Hospital Pontchaillou, Service de Pneumologie
City
Rennes
Country
France
Facility Name
Ruhrlandklinik Essen Westdeutsches Lungenzentrum am Universitätsklinikum Essen GmbH
City
Essen
Country
Germany
Facility Name
Asklepios Fachkliniken München - Gauting Klinik für Pneumologie
City
Gauting
Country
Germany
Facility Name
Thoraxklinik am Universitätsklinikum Heidelberg Abteilung für Pneumologie und Beatmungsmedizin
City
Heidelberg
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein Zentralklinikum Lübeck Medizinische Klinik III - Pneumologie
City
Lübeck
Country
Germany
Facility Name
Attikon University Hospital 2nd Pulmonary Department Athens Medical School National and Kapodistrian University of Athens
City
Athens
Country
Greece
Facility Name
Rabin Medical Center Institute of Pulomonary Medicine
City
Tel Aviv
Country
Israel
Facility Name
S.C. Pneumologia Fondazione IRCCS Policlinico San Matteo
City
Pavia
Country
Italy
Facility Name
St. Antonius Hospital
City
Nieuwegein
Country
Netherlands
Facility Name
Pavlov first Saint Petersburg State Medical Univerisity
City
Saint Petersburg
Country
Russian Federation
Facility Name
Yedikule Pulmonary Diseases and Pulmonary Surgery Training and Research Hospital
City
Istanbul
ZIP/Postal Code
34020
Country
Turkey
Facility Name
Dept. Of Intensive Care Unit Royal Brompton Hospital London
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis
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