Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis

Autoimmune Pulmonary Alveolar Proteinosis Clinical Trial

— IMPALA-X  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03482752
• Other study ID #: SAV006-03
• Status: Completed
• Phase: Phase 3
• Start date: April 16, 2018
• Est. completion date: January 14, 2021

Study information

• Verified date: February 2021
• Source: Savara Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: January 14, 2021
• Est. primary completion date: January 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Autoimmune Diseases
• Autoimmune Pulmonary Alveolar Proteinosis
• Pulmonary Alveolar Proteinosis

Intervention

Drug:
• Molgramostim
300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.

Locations

Country	Name	City	State
Denmark	Dept. Of Respiratory Diseases & Allergy	Århus
France	CHU Rennes Hospital Pontchaillou, Service de Pneumologie	Rennes
Germany	Ruhrlandklinik Essen Westdeutsches Lungenzentrum am Universitätsklinikum Essen GmbH	Essen
Germany	Asklepios Fachkliniken München - Gauting Klinik für Pneumologie	Gauting
Germany	Thoraxklinik am Universitätsklinikum Heidelberg Abteilung für Pneumologie und Beatmungsmedizin	Heidelberg
Germany	Universitätsklinikum Schleswig-Holstein Zentralklinikum Lübeck Medizinische Klinik III - Pneumologie	Lübeck
Greece	Attikon University Hospital 2nd Pulmonary Department Athens Medical School National and Kapodistrian University of Athens	Athens
Israel	Rabin Medical Center Institute of Pulomonary Medicine	Tel Aviv
Italy	S.C. Pneumologia Fondazione IRCCS Policlinico San Matteo	Pavia
Netherlands	St. Antonius Hospital	Nieuwegein
Russian Federation	Pavlov first Saint Petersburg State Medical Univerisity	Saint Petersburg
Turkey	Yedikule Pulmonary Diseases and Pulmonary Surgery Training and Research Hospital	Istanbul
United Kingdom	Dept. Of Intensive Care Unit Royal Brompton Hospital London	London

Sponsors (1)

Lead Sponsor	Collaborator
Savara Inc.

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Greece,  Israel,  Italy,  Netherlands,  Russian Federation,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events		36 months
Primary	Number of serious adverse events		36 months
Primary	Number of adverse drug reactions		36 months
Primary	Number of adverse events leading to treatment discontinuation		36 months
Secondary	Alveolar-arterial oxygen gradient	Difference in oxygen tension between lungs and blood	36 months
Secondary	6-minute walk distance		36 months
Secondary	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
Secondary	Frequency of whole lung lavages during the trial		36 months
Secondary	Diffusion capacity of the lung for carbon monoxide		36 months
Secondary	Forced expiratory volume in one second		36 months
Secondary	Forced vital capacity		36 months
Secondary	Arterial oxygen tension		36 months
Secondary	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
Secondary	Need for oxygen supplement therapy		36 months
Secondary	Number of subjects not requiring treatment for pulmonary alveolar proteinosis		36 months
Secondary	Time off treatment for pulmonary alveolar proteinosis		36 months