Clinical Trial: Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomised, Double-Blind, Placebo-Controlled Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary AlveoLAr Proteinosis Patients "IMPALA"

Brief Summary: This study evaluates inhaled molgramostim (recombinant human (rh) Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)) in the treatment of autoimmune pulmonary alveolar proteinosis patients. A third of the patients will receive inhaled molgramostim daily for 24 weeks, a third will receive inhaled molgramostim every other day for 24 weeks and a third will receive inhaled matching placebo for 24 weeks

Detailed Summary:

The trial is a randomised, double-blind, placebo-controlled multicentre clinical trial investigating efficacy and safety of inhaled molgramostim (rhGM-CSF) in autoimmune pulmonary alveolar proteinosis (aPAP) patients.

The primary objective is efficacy on the Alveolar-arterial oxygen difference after 24-weeks treatment. Secondary objectives are requirement for, and time to, Whole Lung Lavage (WLL), effect on pulmonary function, tolerance to exercise, effect on dyspnea, cough and Quality of Life, and effect on computed tomography (CT) scoring. Number of reported adverse events (AEs), serious AEs, and adverse drug reactions will be monitored.

The trial will include two phases; a Double-blind treatment period consisting of up to eight trial visits (Screening, Baseline, and at Weeks 4,8,12, 16, 20 and 24 after randomisation) and a Follow-up period consisting of up to five trial visits (at Weeks 4, 12, 24, 36 and 48 post-treatment).

In the Double-blind treatment period, eligible subjects will be randomised to treatment for up to 24 weeks with either: 1) inhaled molgramostim (300 µg) once daily, 2) inhaled molgramostim (300 µg) and matching placebo administered intermittently (seven days on and seven days off) or 3) inhaled placebo once daily. During the Double-blind treatment period, WLL may be applied as rescue therapy in case of significant clinical worsening.

Brief risk assessment:

There is currently no approved pharmacological treatment for patients with PAP, and therefore an unmet need for further treatment modalities exists.

Results from pre-clinical studies with inhaled molgramostim nebuliser solution showed the exp
Sponsor: Savara Inc.

Current Primary Outcome: Absolute change from baseline to 24 weeks of Alveolar - arterial oxygen concentration (A-a(DO2)) [ Time Frame: baseline and 24 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of subjects in need of Whole Lung Lavage (WLL) [ Time Frame: 24 weeks ]
  • Time to WLL [ Time Frame: during 24 weeks ]
  • Absolute change from baseline to 24 weeks in Vital Capacity (% predicted) [ Time Frame: baseline and 24 weeks ]


Original Secondary Outcome: Same as current

Information By: Savara Inc.

Dates:
Date Received: February 28, 2016
Date Started: February 2016
Date Completion: December 2018
Last Updated: February 20, 2017
Last Verified: February 2017