Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (aPAP) (IMPALA)
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|ClinicalTrials.gov Identifier: NCT02702180|
Recruitment Status : Recruiting
First Posted : March 8, 2016
Last Update Posted : April 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Autoimmune Pulmonary Alveolar Proteinosis||Drug: molgramostim Drug: placebo||Phase 2 Phase 3|
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 tolerance to exercise, effect on Quality of Life, time to Whole Lung Lavage (WLL), effect on pulmonary function, effect on dyspnea and cough, 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 trial, WLL may be applied as rescue therapy in case of significant clinical worsening. In the Follow-up period, open-label treatment with molgramostim will be provided.
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 expected pharmacological effects on white blood cell (WBC) populations locally and systemically in line with observed effects after IV administration of molgramostim. No severe, serious or dose-limiting AEs were observed in the first clinical study in humans (MOL-001). The most common AE was cough, which was reported at a similar incidence for the molgramostim nebuliser solution and placebo. Increases of WBC populations in the blood consistent with the known mechanism of action were observed; most of which were considered not clinically significant. Only two cases (total WBC increased and eosinophilia) were reported as AEs. No development of anti-drug antibodies was observed.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||135 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomised, Double-Blind, Placebo-Controlled Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary AlveoLAr Proteinosis Patients "IMPALA"|
|Actual Study Start Date :||February 2016|
|Estimated Primary Completion Date :||March 2019|
|Estimated Study Completion Date :||September 2019|
Experimental: molgramostim continuously
Inhalation of molgramostim nebuliser solution (rhGM-CSF) 300 mcg once daily for 24 weeks
molgramostim nebuliser solution
Other Name: rhGM-CSF
Experimental: molgramostim intermittently
Inhalation of molgramostim nebuliser solution (rhGM-CSF) 300 mcg for seven days and placebo nebuliser solution for seven days for 24 weeks (12 cycles)
molgramostim nebuliser solution
Other Name: rhGM-CSFDrug: placebo
placebo nebuliser solution
Placebo Comparator: placebo
Inhalation of placebo nebuliser solution once daily for 24 weeks
placebo nebuliser solution
- Absolute change from baseline to 24 weeks of Alveolar - arterial oxygen concentration (A-a(DO2)) [ Time Frame: baseline and 24 weeks ]
- Change from baseline in 6-minute walking distance after 24-weeks treatment [ Time Frame: baseline and 24 weeks ]
- Change from baseline in St. George's respiratory questionnaire total score after 24-weeks treatment [ Time Frame: baseline and 24 weeks ]
- Time to whole lung lavage during 24-weeks treatment [ Time Frame: 24 weeks ]
- Number of adverse events during 24-weeks treatment [ Time Frame: during 24 weeks ]
- Number of serious adverse events during 24-weeks treatment [ Time Frame: during 24 weeks ]
- Number of adverse drug reactions during 24-weeks treatment [ Time Frame: during 24 weeks ]
- Number of severe adverse events during 24-weeks treatment [ Time Frame: during 24 weeks ]
- Number of adverse events leading to treatment discontinuation during 24-weeks treatment [ Time Frame: during 24 weeks ]
- Change from baseline to 24 weeks in pulmonary function tests [ Time Frame: baseline and 24 weeks ]
- Change from baseline to 24 weeks in dyspnoea and cough scores [ Time Frame: baseline and 24 weeks ]
- Number of subjects with improved CT score after 24-weeks treatment [ Time Frame: baseline and 24 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02702180
|Contact: Mikkel Walmaremail@example.com|
|Contact: Cecilia Ganslandt, MDfirstname.lastname@example.org|
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|Principal Investigator:||Cliff Morgan, MD||Royal Brompton Hospital London|