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.

Tracking Information

• First Submitted Date: March 21, 2018
• First Posted Date: March 29, 2018
• Last Update Posted Date: February 3, 2021
• Actual Study Start Date: April 16, 2018
• Actual Primary Completion Date: January 14, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 28, 2018)

• Number of adverse events [ Time Frame: 36 months ]
• Number of serious adverse events [ Time Frame: 36 months ]
• Number of adverse drug reactions [ Time Frame: 36 months ]
• Number of adverse events leading to treatment discontinuation [ Time Frame: 36 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 28, 2018)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

Open Label, Non-controlled

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Autoimmune Pulmonary Alveolar Proteinosis

Intervention

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

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 2, 2021): 62
• Original Estimated Enrollment (submitted: March 28, 2018): 60
• Actual Study Completion Date: January 14, 2021
• Actual Primary Completion Date: January 14, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, France, Germany, Greece, Israel, Italy, Netherlands, Russian Federation, Turkey, United Kingdom

Administrative Information

• NCT Number: NCT03482752
• Other Study ID Numbers: SAV006-03
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Savara Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Savara Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Savara Inc.
• Verification Date: February 2021