The IMPALA-2 trial

Breathing new life into autoimmune pulmonary alveolar proteinosis (aPAP) research

Thank you for your interest in this rare disease clinical trial. Your patient referrals could help advance research toward a possible treatment for aPAP.

Why we are conducting the IMPALA-2 clinical trial

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease with no approved pharmacologic treatment options. This condition belongs to a family of distinct rare lung diseases collectively referred to as PAP. Autoimmune Pulmonary Alveolar Proteinosis represents about 90% of all patients with PAP.

PAP is characterized by the build-up of surfactant in the alveoli (air sacs) of the lungs. The surfactant consists of proteins and lipids and is an important physiological substance that lines the inside of the alveoli to prevent the lungs from collapsing. The lungs continuously produce new active surfactant. In a healthy lung, the surfactant is cleared by immune cells called alveolar macrophages. However, in lungs of patients with aPAP, the macrophages do not effectively clear the surfactant from the alveoli, leading to gradual accumulation of surfactant in the alveoli. The root cause of aPAP is an autoimmune response against granulocyte-macrophage colony-stimulating factor (GM-CSF), a naturally occurring protein in the body. Pulmonary macrophages need to be stimulated by GM-CSF to function properly, but in aPAP, GM-CSF is neutralized by antibodies against GM-CSF, rendering the macrophages unable to perform their tasks effectively, including the clearance of surfactant from the alveoli.

As a result of the accumulation of surfactant, oxygen transfer in the lungs is reduced and patients start to experience shortness of breath and decreased exercise tolerance as early symptoms. Typically, shortness of breath is first observed upon exertion, but as the disease progresses, shortness of breath can be experienced even when a person is at rest. Patients may experience cough, as well as episodes of fever, especially if secondary lung infection develops. In the long-term, the disease can lead to serious complications, including lung fibrosis and the need for lung transplant.

Details on the IMPALA-2 clinical trial

aPAP clinical trial design

The IMPALA-2 aPAP clinical trial is assessing the safety and efficacy of molgramostim nebulizer solution (molgramostim), an inhaled investigational drug, versus placebo for 48 weeks plus a 48-week open-label extension in adults with aPAP. Both molgramostim and placebo are administered on top of the current standard of care, which includes supplemental oxygen when required and rescue treatment with whole lung lavage, if needed.
  • Screening period: 6 weeks to determine eligibility
  • Double-blind treatment period: 48 weeks; participants receive molgramostim or placebo (1:1 randomization)
  • Open-label treatment period: 48 weeks; all participants receive molgramostim
  • Safety follow up: 4 weeks

The science behind this investigational rare disease treatment

Molgramostim is a non-glycosylated form of a recombinant protein known as GM-CSF. GM-CSF is known to impact immune system response and has a key role in surfactant homeostasis and alveolar epithelial repair. Results from investigator-sponsored clinical trials and case studies indicate that GM-CSF may have a positive impact on oxygenation and clinical symptoms in aPAP patients.
Data from the first Phase 2/3 IMPALA clinical trial suggest that molgramostim may improve lung pathology, pathophysiology, and health status. Based on these findings, which were published in the New England Journal of Medicine in September 2020, the IMPALA-2 clinical trial is being conducted to further investigate the potential efficacy and safety of molgramostim in aPAP.

Patient inclusion criteria for the IMPALA-2 clinical trial

  • At least 18 years of age (must be at least 20 years of age if participating in Japan)
  • History of aPAP (to be confirmed by serum anti-GM-CSF antibody test at screening)
  • Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤70% predicted
  • Has not recently undergone whole lung lavage (last procedure must be ≥3 months prior to baseline)

Patients must also meet additional eligibility criteria in order to participate in the IMPALA-2 clinical trial.

If you would like to refer a patient, please find a clinical trial site below.

Still have questions? Read our FAQs.

  1. Canada
  2. United States
  3. Ireland
  4. United Kingdom
  5. Portugal
  6. Spain
  7. France
  8. Belgium
  9. Netherlands
  10. Germany
  11. Italy
  12. Poland
  13. Romania
  14. Greece
  15. Turkey
  16. South Korea
  17. Japan
  18. Australia

How do I know if my patient is eligible?

In addition to the eligibility criteria outlined above, inclusion and exclusion criteria are listed on clinicaltrials.gov.

Where can I go for additional information?

All relevant study details and study contact information can be found on clinicaltrials.gov.

Who is the study sponsor?

The study is sponsored by Savara Inc.

How do I refer a patient or find a participating site?

The most up-to-date list of study locations currently recruiting can be found on clinicaltrials.gov.

My patient lives far away from a site. How can they participate?

Some patients may be eligible for trial-related travel reimbursement, contact the study sponsor for details. You can find the study sponsor contact details on clinicaltrials.gov.