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

NCT01511068 | Completed Phase 2 Results DMC

• 1 other identifier: 2011-0959_CCHMC_IRB
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

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.

Conditions

Hereditary Pulmonary Alveolar Proteinosis

Keywords

PAP

Outcome Measures

Primary Outcomes (2)

• Change in Time (Minutes) to Discontinuation of Exercise During a Standardized Treadmill Exercise Test

  A modified Bruce protocol stress test was used to evaluate improvement in blood oxygen saturation (SpO2). A pulse-oximeter was placed on the participant's finger with the participant at rest while sitting in a chair. Leads for the electrocardiograph were placed on the chest wall. The treadmill was started at 1.7 miles per hour (mph) and a grade of 0%. At three minute intervals, the speed increased as follows: 1.7 mph, 1.7 mph, 1.7 mph, 2.5 mph, 3.4 mph, 4.2 mph, 5.0 mph, 5.5 mph, 6.0 mph, 6.5 mph, 7.0 mph, and 7.5 mph. The participant stopped the test due to intolerable dyspnea or if the SpO2 fell below 88%.

  Baseline, 7 months

• Change in Minimum Pulse Oximetry During a Standardized Treadmill Exercise Test

  A modified Bruce protocol stress test was used to evaluate improvement in blood oxygen saturation (SpO2). A pulse-oximeter was placed on the participant's finger with the participant at rest while sitting in a chair. Leads for the electrocardiograph were placed on the chest wall. The treadmill was started at 1.7 miles per hour (mph) and a grade of 0%. At three minute intervals, the speed increased as follows: 1.7 mph, 1.7 mph, 1.7 mph, 2.5 mph, 3.4 mph, 4.2 mph, 5.0 mph, 5.5 mph, 6.0 mph, 6.5 mph, 7.0 mph, and 7.5 mph. The participant stopped the test due to intolerable dyspnea or if the SpO2 fell below 88%.

  Baseline, 7 months

Secondary Outcomes (8)

• Change in Diffusion Capacity for Carbon Monoxide

  Baseline, 7 months

• Change in Minimum Pulse Oximetry During a Standardized Exercise Protocol Oximetry

  Baseline, 7 months

• Change in Radiographic Evidence of PAP Lung Disease

  Baseline, 7 months

• Change in Quality of Life

  Baseline, 7 months

• Change in Dyspnea Symptom Score

  Baseline, 7 months

Study Arms (1)

Inhaled Leukine (rhGM-CSF)

EXPERIMENTAL

Inhaled recombinant human GM-CSF in individuals with hereditary Pulmonary Alveolar Proteinosis (hPAP) due to partial dysfunction of the GM-CSF receptor

Drug: Leukine

Interventions

Leukine DRUG

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.

Also known as: GM-CSF [Leukine (Sargramostim)]

Inhaled Leukine (rhGM-CSF)

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Virginia Commonwealth University: collaborator
• Genzyme, a Sanofi Company: collaborator

Study Sites (2)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298-0646, United States

Location

MeSH Terms

Interventions

sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Bruce Trapnell
• Organization: Cincinnati Children's Hospital Medical Center

Bruce.Trapnell@cchmc.org

513636-6361

Study Officials

• Bruce Trapnell, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Bruce Rubin, MD, FRCPC

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2011
• First Posted: January 18, 2012
• Study Start: August 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2014
• Last Updated: August 30, 2023
• Results First Posted: September 1, 2020

Record last verified: 2023-08

Locations

US (2)