Autoimmune Pulmonary Alveolar Proteinosis (aPAP) MedDRA version: 21.1 Level: LLT Classification code 10037316 Term: Pulmonary alveolar proteinosis System Organ Class: 100000004855
Conditions
Sponsors
Savara ApS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must be =18 years of age, at the time of signing the informed consent. Specific for Japan; Subject must be =20 years of age, at the time of signing the informed consent. 2. A serum anti-GM-CSF autoantibody test result confirming autoimmune PAP. 3. History of PAP, based on examination of a lung biopsy, bronchoalveolar lavage (BAL) cytology, or a high-resolution computed tomogram (HRCT) of the chest. 4. DLCO 70% predicted or lower at the first screening and Baseline visits. 5. Change in % predicted DLCO of 85% during 15 minutes without use of supplemental oxygen at the Screening visits. 8. Male or female 9. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male subjects: Males agreeing to use condoms during and until 30 days after last dose of trial treatment, or males having a female partner who is using adequate contraception as described below. b. Female subjects: Females who have been post-menopausal for >1 year, or females of childbearing potential after a confirmed menstrual period using a highly efficient method of contraception (i.e. a method with =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Diagnosis of hereditary or secondary PAP, or a metabolic disorder of surfactant production. 2. WLL performed within 3 months prior to baseline. 3. Requirement for WLL at screening or baseline. 4. GM-CSF treatment within 6 months prior to baseline. 5. Treatment with rituximab within 6 months prior to baseline. 6. Treatment with plasmapheresis within 6 weeks months prior to baseline. 7. Treatment with any investigational medicinal product within 5 half-lives or 3 months (whichever is longer) prior to baseline. 8. Previously randomized in this trial. 9. History of allergic reactions to GM-CSF or any of the excipients in the nebulizer solution. 10. Inflammatory or autoimmune disease of a severity that necessitates significant (e.g. more than 10 mg/day systemic prednisolone) immunosuppression. 11. Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product. 12. History of, or present, myeloproliferative disease or leukemia. 13. Apparent pre-existing concurrent pulmonary fibrosis, or diagnosis of interstitial lung disease other than aPAP. 14.Acute or unstable cardiac or pulmonary disease that may be aggravated by exercise or confound assessment of the primary endpoint: including presence of pulmonary edema, or diagnosis of chronic obstructive pulmonary disease (COPD), pulmonary vasculitis, or pulmonary hypertension. 15. Known active infection (viral, bacterial, fungal, or mycobacterial) that may affect the efficacy evaluation in the trial. 16. Physical disability or other condition that precludes safe and adequate exercise testing. 17. Any other serious medical condition which in the opinion of the Investigator would make the subject unsuitable for the trial 18. Pregnant, planning to become pregnant during the trial, or breastfeeding woman.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Investigate the efficacy of Molgramostim 300 µg nebulizer solution compared to placebo ;Secondary Objective: - Investigate the safety of MOL compared to placebo - Investigate the safety of MOL compared to placebo after 96-week treatment ;Primary end point(s): Change in % predicted DLCO from baseline to Week 24;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in % predicted DLCO from baseline to Week 48 • Change in SGRQ Total from baseline to Week 24 • Change in SGRQ Activity from baseline to Week 24 • Change in EC (expressed as peak METs) from baseline to Week 24 • Change in SGRQ Total from baseline to Week 48 • Change in SGRQ Activity from baseline to Week 48 • Change in EC (expressed as peak METs) from baseline to Week 48 ;Timepoint(s) of evaluation of this end point: Week 24 | — |
Countries
Belgium, Canada, France, Germany, Ireland, Italy, Japan, Korea, Republic of, Netherlands, Poland, Romania, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Operations
Savara ApS
Outcome results
None listed