Clinical trial NCT01511068: Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Hereditary Pulmonary Alveolar Proteinosis (PAP)
Official title: Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Hereditary Pulmonary Alveolar Proteinosis (PAP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hereditary Pulmonary Alveolar Proteinosis
Keywords: PAP
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Virginia Commonwealth University
name: Genzyme, a Sanofi Company
First posted: 2012-01-18
Enrollment: 2
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the therapeutic efficacy of inhaled recombinant human GM-CSF in individuals with hereditary Pulmonary Alveolar Proteinosis (PAP) due to partial dysfunction of the GM-CSF receptor.


Eligibility criteria: Inclusion Criteria:

* A diagnosis of PAP caused by bi-allelic mutations in CSF2RA or CSF2RB associated with impaired GM-CSF-R-alpha or GM-CSF-R-beta function, respectively, resulting in reduced but non-zero GM-CSF signaling
* Able and willing to give written informed consent / assent as necessary
* Clinically stable

Exclusion Criteria:

* Confirmed diagnosis of a disorder of surfactant production caused by bi-allelic mutations in ABCA3, SFTPB, or SFTPC
* Confirmed diagnosis of autoimmune PAP caused by a high level of GM-CSF autoantibody
* Confirmed diagnosis of secondary PAP caused by an underlying clinical disorder known to be associated with the development of PAP, e.g., inhalation of silica or titanium; myelodysplasia and others
* Treatment with any investigational agent in the 3 months prior to enrollment
* History of severe allergic or anaphylactic reactions to GM-CSF or other yeast-derived products
* History of asthma or other reactive airways disease
* Known active, viral, fungal, mycobacterial, or other infection
* A serious medical condition which, in the opinion of the investigator or data and safety monitoring committee, would make the patient unsuitable for the study

Primary outcomes:
measure: Change in Time (Minutes) to Discontinuation of Exercise During a Standardized Treadmill Exercise Test
timeFrame: Baseline, 7 months
measure: Change in Minimum Pulse Oximetry During a Standardized Treadmill Exercise Test
timeFrame: Baseline, 7 months
Secondary outcomes:
measure: Change in Diffusion Capacity for Carbon Monoxide
timeFrame: Baseline, 7 months
measure: Change in Minimum Pulse Oximetry During a Standardized Exercise Protocol Oximetry
timeFrame: Baseline, 7 months
measure: Change in Radiographic Evidence of PAP Lung Disease
timeFrame: Baseline, 7 months
measure: Change in Quality of Life
timeFrame: Baseline, 7 months
measure: Change in Dyspnea Symptom Score
timeFrame: Baseline, 7 months
measure: Change in Serum Anti-GM-CSF Antibodies Levels
timeFrame: Baseline and monthly up to 7 months
measure: Change in Serum Biomarkers - GM-CSF
timeFrame: Baseline and monthly up to 7 months
measure: Change in Serum Biomarkers - Surfactant Protein D
timeFrame: Baseline and monthly up to 7 months
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Bruce Trapnell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Commonwealth University
name: Bruce Rubin, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: