Autoimmune Pulmonary Alveolar Proteinosis (aPAP) MedDRA version: 20.0 Level: LLT Classification code 10037316 Term: Pulmonary alveolar proteinosis System Organ Class: 100000004855
Conditions
Interventions
Product Name: Molgramostim 300 mcg nebuliser solution
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: MOLGRAMOSTIM
CAS Number: 99283-10-0
Sponsors
Savara ApS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - aPAP diagnosed by CT, or by biopsy, or by Broncho Alveolar Lavage (BAL), and by increased GM-CSF autoantibodies in serum - Stable or progressive aPAP (i.e. absolute VC not improved by more than 5% and/or DLCO not improved by more than 10% - assessed from medical records) during a minimum period of two months prior to the Baseline visit - PaO2 4 percentage points on the 6 Minute Walk Test (6MWT) - An (A-a)DO2 of minimum 25 mmHg/3.33 kPa - Female or male =18 years of age - 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 35
Exclusion criteria
Exclusion criteria: - Diagnosis of hereditary or secondary pulmonary alveolar proteinosis (PAP) - WLL within one month of Baseline - Treatment with GM-CSF within three months of Baseline - Treatment with rituximab within six months of Baseline - Treatment with plasmapheresis within three months of Baseline - Treatment with any investigational medicinal product within four weeks of Screening - Concomitant use of sputum modifying drugs such as carbocystein or ambroxol - 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 - Known active infection (viral, bacterial, fungal or mycobacterial) - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare efficacy of inhaled molgramostim on the Alveolar-arterial oxygen difference ((A-a)DO2) with placebo after 24-weeks treatment. ; Secondary Objective: Key Secondary objectives: - To compare efficacy of inhaled molgramostim on tolerance to exercise with placebo after 24-weeks of treatment - To compare efficacy of inhaled molgramostim on respiratory disease-related quality of life with placebo after 24-weeks of treatment - To compare efficacy of inhaled molgramostim based on time to Whole Lung Lavage (WLL) with placebo during 24-weeks of treatment. - To compare safety of inhaled molgramostim with placebo in terms of reported adverse events (AEs), serious adverse events (SAEs), adverse drug reactions (ADRs), severe AEs and withdrawals due to AEs during 24-weeks treatment ;Primary end point(s): Absolute change from baseline of (A-a)DO2 after 24-weeks treatment;Timepoint(s) of evaluation of this end point: After 24-weeks treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: See E.5.2; Secondary end point(s): Key Secondary Endpoints: - Change from baseline in 6MWD after 24-weeks treatment - Change from baseline in SGRQ total score after 24-weeks treatment - Time to WLL during 24-weeks treatment - Number of AEs, SAEs, ADRs, severe AEs and AEs leading to treatment discontinuation, including clinically significant changes in laboratory tests and electrocardiogram(ECG) variables, during 24-weeks treatment Further Secondary Endpoints: - Absolute change from baseline in VC (% predicted), DLCO (% predicted), FEV1 (% predicted), FVC (% predicted) and and relative change from baseline in PaO2 after 24-weeks treatment - Number of subjects with >5 mmHg/>0.67 kPa and number of subjects with >10 mmHg/>1.33 kPa improvement in (A-a)DO2 after 24-weeks treatment - Number of subjects with >5 percentage points and number of subjects with >10 percentage points improvement in VC (% predicted) after 24-weeks treatment - Number of subjects with >10 percentage points improvement in DLCO (% predicted) after 24 weeks treatment - Number of subjects with >10 percentage points improvement in FEV1 (% predicted) and FVC (% predicted) after 24-weeks treatment - Number of subjects with >10% relative improvement in PaO2 after 24-weeks treatment - Number of subjects with improved tolerance to exercise (increase in distance walked =50 m or desaturation <4 percentage points on the 6MWT) after 24-weeks treatment - Change from baseline in dyspnoea score and cough scores after 24-weeks treatment - Number of subjects with improved CT score after 24-weeks treatment Exploratory Endpoints: Double-blind treatment period - Abso | — |
Countries
Australia, Denmark, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactTrial director
Savara ApS
Outcome results
None listed