Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis

Study Overview
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Brief Summary
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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.

Official Title
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An Open-label, Non-controlled, Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis Patients

Conditions
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Autoimmune Pulmonary Alveolar Proteinosis

Intervention / Treatment
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* Drug: Molgramostim


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Open Label, Non-controlled
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Molgramostim|300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events |  | 36 months | 
| Number of serious adverse events |  | 36 months | 
| Number of adverse drug reactions |  | 36 months | 
| Number of adverse events leading to treatment discontinuation |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alveolar-arterial oxygen gradient | Difference in oxygen tension between lungs and blood | 36 months | 
| 6-minute walk distance |  | 36 months | 
| 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. | 36 months | 
| Frequency of whole lung lavages during the trial |  | 36 months | 
| Diffusion capacity of the lung for carbon monoxide |  | 36 months | 
| Forced expiratory volume in one second |  | 36 months | 
| Forced vital capacity |  | 36 months | 
| Arterial oxygen tension |  | 36 months | 
| 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. | 36 months | 
| Need for oxygen supplement therapy |  | 36 months | 
| Number of subjects not requiring treatment for pulmonary alveolar proteinosis |  | 36 months | 
| Time off treatment for pulmonary alveolar proteinosis |  | 36 months |