Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis (IMPALA-X)

• ClinicalTrials.gov Identifier: NCT03482752
• Recruitment Status: Completed
• First Posted: March 29, 2018
• Last Update Posted: February 3, 2021
• Sponsor: Savara Inc.
• Information provided by (Responsible Party): Savara Inc.

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.

Condition or disease	Intervention/treatment	Phase
Autoimmune Pulmonary Alveolar Proteinosis	Drug: Molgramostim	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open Label, Non-controlled
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Non-controlled, Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis Patients
• Actual Study Start Date: April 16, 2018
• Actual Primary Completion Date: January 14, 2021
• Actual Study Completion Date: January 14, 2021

Arms and Interventions

Intervention Details:

• Drug: Molgramostim
  300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
  Other Name: Recombinant human GM-CSF

Outcome Measures

Primary Outcome Measures :

1. Number of adverse events [ Time Frame: 36 months ]
2. Number of serious adverse events [ Time Frame: 36 months ]
3. Number of adverse drug reactions [ Time Frame: 36 months ]
4. Number of adverse events leading to treatment discontinuation [ Time Frame: 36 months ]

Secondary Outcome Measures :

1. Alveolar-arterial oxygen gradient [ Time Frame: 36 months ]
   Difference in oxygen tension between lungs and blood
2. 6-minute walk distance [ Time Frame: 36 months ]
3. St Georges Respiratory Questionnaire total score [ Time Frame: 36 months ]
   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.
4. Frequency of whole lung lavages during the trial [ Time Frame: 36 months ]
5. Diffusion capacity of the lung for carbon monoxide [ Time Frame: 36 months ]
6. Forced expiratory volume in one second [ Time Frame: 36 months ]
7. Forced vital capacity [ Time Frame: 36 months ]
8. Arterial oxygen tension [ Time Frame: 36 months ]
9. Pulmonary alveolar proteinosis Disease Severity Score [ Time Frame: 36 months ]
   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.
10. Need for oxygen supplement therapy [ Time Frame: 36 months ]
11. Number of subjects not requiring treatment for pulmonary alveolar proteinosis [ Time Frame: 36 months ]
12. Time off treatment for pulmonary alveolar proteinosis [ Time Frame: 36 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Denmark

Dept. Of Respiratory Diseases & Allergy

Århus, Denmark

France

CHU Rennes Hospital Pontchaillou, Service de Pneumologie

Rennes, France

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, Germany

Greece

Attikon University Hospital 2nd Pulmonary Department Athens Medical School National and Kapodistrian University of Athens

Athens, Greece

Israel

Rabin Medical Center Institute of Pulomonary Medicine

Tel Aviv, Israel

Italy

S.C. Pneumologia Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

Netherlands

St. Antonius Hospital

Nieuwegein, Netherlands

Russian Federation

Pavlov first Saint Petersburg State Medical Univerisity

Saint Petersburg, Russian Federation

Turkey

Yedikule Pulmonary Diseases and Pulmonary Surgery Training and Research Hospital

Istanbul, Turkey, 34020

United Kingdom

Dept. Of Intensive Care Unit Royal Brompton Hospital London

London, United Kingdom

Sponsors and Collaborators

Savara Inc.

Investigators

• Principal Investigator: Francesco Bonella, Prof.; Interstitial and Rare Lung Disease Unit, Ruhrlandklinik University Hospital, Essen, Germany

More Information

• Responsible Party: Savara Inc.
• ClinicalTrials.gov Identifier: NCT03482752
• Other Study ID Numbers: SAV006-03
• First Posted: March 29, 2018
• Last Update Posted: February 3, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pulmonary Alveolar Proteinosis; Autoimmune Diseases; Lung Diseases; Respiratory Tract Diseases; Immune System Diseases; Molgramostim; Sargramostim; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs