Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis

Phase 3

Terminated

Brief Summary: SAV006-03 is an open-label extension study for participants who had completed the IMPALA study.

At the baseline visit, eligible participants 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.

Participants will be treated with inhaled molgramostim for up to 36 months.

During the trial, whole lung lavage will be applied as rescue therapy.

Recruitment & 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.

Arm && Interventions

Group	Intervention	Description
Molgramostim nebulizer solution (300 μg)	Molgramostim	Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment).

Primary Outcome Measures

Name	Time	Method
Number of Treatment-emergent Adverse Events (TEAEs)	139 weeks	The primary objective of this trial was safety assessed by adverse event (AE) reporting. Definitions and reporting procedures for AEs were done according to current regulatory standards. AEs were collected by the investigator by a non-leading question 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. Treatment-emergent was defined as events occurring on study drug and up to 7 days after last dose of study drug.
Number of TEAEs Leading to Treatment Discontinuation	139 weeks
Number of Serious TEAEs	139 weeks	Serious TEAEs were 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 abnormality or birth defect * May jeopardise the participant or may require medical intervention to prevent one or more of the outcomes listed above (Important Medical Events).
Number of Treatment-emergent Adverse Drug Reactions (ADRs)	139 weeks	All AEs were assessed by the investigator for causality (unlikely, possible, probable, not applicable) according to current regulatory standards. AEs which had a 'possible' or 'probable' causality were classified as ADRs.

Secondary Outcome Measures

Name	Time	Method

Locations (13): Dept. Of Respiratory Diseases & Allergy
🇩🇰
Århus, Denmark
CHU Rennes Hospital Pontchaillou, Service de Pneumologie
🇫🇷
Rennes, France
Ruhrlandklinik Essen Westdeutsches Lungenzentrum am Universitätsklinikum Essen GmbH
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Essen, Germany
Asklepios Fachkliniken München - Gauting Klinik für Pneumologie
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Gauting, Germany
Thoraxklinik am Universitätsklinikum Heidelberg Abteilung für Pneumologie und Beatmungsmedizin
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Heidelberg, Germany
Universitätsklinikum Schleswig-Holstein Zentralklinikum Lübeck Medizinische Klinik III - Pneumologie
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Lübeck, Germany
Rabin Medical Center Institute of Pulomonary Medicine
🇮🇱
Tel Aviv, Israel
S.C. Pneumologia Fondazione IRCCS Policlinico San Matteo
🇮🇹
Pavia, Italy
Yedikule Pulmonary Diseases and Pulmonary Surgery Training and Research Hospital
🇹🇷
Istanbul, Turkey
Dept. Of Intensive Care Unit Royal Brompton Hospital London
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London, United Kingdom
Attikon University Hospital 2nd Pulmonary Department Athens Medical School National and Kapodistrian University of Athens
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Athens, Greece
St. Antonius Hospital
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Nieuwegein, Netherlands
Pavlov first Saint Petersburg State Medical Univerisity
🇷🇺
Saint Petersburg, Russian Federation