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Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Hereditary Pulmonary Alveolar Proteinosis (PAP) (FAMPAP)

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Virginia Commonwealth University
Genzyme
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01511068
First received: December 12, 2011
Last updated: January 7, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Hereditary Pulmonary Alveolar Proteinosis
 Drug: Leukine
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Hereditary Pulmonary Alveolar Proteinosis (PAP)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Time for the oxygen saturation to fall below 88% [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improvement in pulmonary function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Improvement in exercise tolerance [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Improvement in CT scan [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Improvement in Quality of Life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Improvement in dyspnea and fatigue [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Biomarkers will be assayed to detect changes from baseline values: surfactant protein-D (SP-D), KL-6, CEA), GM-CSF, GM-CSF autoantibodies, macrophage colony stimulating factor (M-CSF), and macrophage inflammatory protein -1 alpha MIP-1alpha. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 2
Study Start Date: August 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: inhaled recombinant
inhaled recombinant human GM-CSF in individuals with hereditary Pulmonary Alveolar Proteinosis (PAP) due to partial dysfunction of the GM-CSF receptor
 Drug: Leukine
Participants will receive inhaled rhGM-CSF (Sargramostim, Leukine) at the dose of 250 mcg one time per week for 12 weeks. Following an interim safety evaluation, participants may be entered into a second 12 week treatment period where participants will receive either 250 mcg or 500 mcg once weekly. At the end of any treatment period, participants will be followed for 12 additional weeks in the absence of inhaled rhGM-CSF to evaluate safety and efficacy.
Other Name: GM-CSF [Leukine (Sargramostim)]

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01511068

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0646
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Virginia Commonwealth University
Genzyme
Investigators
Principal Investigator: Bruce Trapnell, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Bruce Rubin, MD, FRCPC Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01511068     History of Changes
Obsolete Identifiers: NCT01534156
Other Study ID Numbers: 2011-0959_CCHMC_IRB
Study First Received: December 12, 2011
Last Updated: January 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Medical Center, Cincinnati:
PAP

Additional relevant MeSH terms:
Pulmonary Alveolar Proteinosis
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 16, 2013