Inhalation of Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Autoimmune Pulmonary Alveolar Proteinosis (PAP)

• ClinicalTrials.gov Identifier: NCT02243228
• Recruitment Status: Unknown
• First Posted: September 17, 2014
• Last Update Posted: September 17, 2014
• Sponsor: Peking Union Medical College Hospital
• Collaborator: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Information provided by (Responsible Party): Kaifeng Xu, Peking Union Medical College Hospital

Tracking Information

• First Submitted Date: September 14, 2014
• First Posted Date: September 17, 2014
• Last Update Posted Date: September 17, 2014
• Study Start Date: August 2014
• Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 16, 2014): A-aDO2 difference [ Time Frame: 2 years ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 16, 2014)

• Time to relapse [ Time Frame: up to 2 years ]
  The definition of relapse were as follow: 1) newly requirement for whole lung lavage (WLL); or 2) PAP associated death; or 3) a reduction in PaO2 of more than 10mmHg, or an increase in DA-aO2 of more than 10mmHg; or 4) a worsen chest HRCT.
• FEV1 difference [ Time Frame: 2 years ]
• 6 minutes walking distance difference [ Time Frame: 2 years ]
• Severe adverse event [ Time Frame: 2 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Inhalation of Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Autoimmune Pulmonary Alveolar Proteinosis (PAP)
• Official Title: A Prospective Study of Inhaling Granulocyte-macrophage Colony Stimulating Factor in Adult Patients With Mild-to-moderate Autoimmune Pulmonary Alveolar Proteinosis in China: a Randomized Open-label Study
• Brief Summary: The purpose of the study is to evaluate if inhaled granulocyte-macrophage colony stimulating factor delay the increase in alveolar-arterial oxygen difference, compared to no treatment, for adult patients with mild-to-moderate autoimmune pulmonary alveolar proteinosis in China over a two-year period.

Detailed Description

Autoimmune pulmonary alveolar proteinosis (PAP, previously known as idiopathic PAP) is a rare interstitial lung disease elicited by the formation of autoantibodies which neutralize the activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) which decreases macrophage clearance of surfactant.

Currently, the standard treatment strategy for PAP is whole lung lavage (WLL)，which is invasive and has limitations. Inhaled GM-CSF therapy became a new option for PAP patients not only because of its effectiveness and safety, but it is convenient way for patients who are reluctant to do operation as well. We are planning to prospectively evaluate if inhaled granulocyte-macrophage colony stimulating factor would delay the increase in alveolar-arterial oxygen difference (A-aDO2, which is the most sensitive factor in evaluating APAP5), compared to placebo, for patients with mild-to-moderate autoimmune pulmonary alveolar over a two-year period.

A total of 42 subjects with APAP who meet the inclusion criteria will be enrolled at Peking Union Medical College Hospital and Nanjing Drum Tower Hospital. After observe APAP patients for 3 months to rule out patients who resolved spontaneously, the participants will undergo randomization (by random number table)and stratified into two different groups by their DSS. Then they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week or no treatment for 6 months, and will be followed on an outpatient basis at 2 weeks, and 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after initiation of therapy.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Autoimmune Pulmonary Alveolar Proteinosis

Intervention

Drug: GM-CSF

Other Name: HUABEI JIMUXIN

Study Arms

Experimental: GM-CSF, nebulizer

After the patients were randomly divided into two groups, they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week for 6 months.

Intervention: Drug: GM-CSF

• Publications *: Tian X, Yang Y, Chen L, Sui X, Xu W, Li X, Guo X, Liu L, Situ Y, Wang J, Zhao Y, Meng S, Song W, Xiao Y, Xu KF. Inhaled granulocyte-macrophage colony stimulating factor for mild-to-moderate autoimmune pulmonary alveolar proteinosis - a six month phase II randomized study with 24 months of follow-up. Orphanet J Rare Dis. 2020 Jul 2;15(1):174. doi: 10.1186/s13023-020-01450-4.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: September 16, 2014): 42
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2017
• Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Accessible population:

Adult patients with mild-to-moderate autoimmune pulmonary alveolar and without spontaneous remission will be enrolled at Peking Union Medical College Hospital and Nanjing Drum Tower Hospital.

Inclusion Criteria:

• Adult autoimmune PAP subjects will be included: 1) a positive PAS stain from BALF or lung biopsy; 2) high level of serum anti-GM-CSF antibody (>2.39ug/ml, the cut-off point in our hospital); 3) age above 18 years old; 4) exclude hereditary and secondary PAP.
• Able to give written informed consent and comply with the requirements of the study.
• Patients are not eligible for the whole lung lavage (WLL), decided by clinicians.
• Eligibility for GM-CSF inhalation: 1) Disease severity score (DSS) is 1-3; 2) No treatment with GM-CSF therapy or WLLin the 3 months prior to enrollment. Definition of DSS2: 1, no symptom and PaO2>=70mmHg；2, PaO2>=70mmHg with symptoms；3, PaO2>=60 and <70mmHg; 4, PaO2>=50 and <60mmHg; 5, PaO2<50mmHg.

Exclusion Criteria:

• Patients will be observed for 3 months and all APAP patients who resolved spontaneously will be excluded from our study.
• PAP resulting from another condition (e.g. occupational exposure to silica, underlying HIV, respiratory infections, myeloproliferative disorder or leukaemia);
• A normal or low-titre serum anti-GM-CSF antibody (≤2.39ug/ml);
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies；
• Chronic lung disease associated with already existing respiratory failure (such as pulmonary emphysema or fibrosis);
• Other serious medical conditions which, in the opinion of the investigator, would make the patient unsuitable for the study.
• Pregnancy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02243228
• Other Study ID Numbers: XT 01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kaifeng Xu, Peking Union Medical College Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Peking Union Medical College Hospital
• Original Study Sponsor: Same as current
• Collaborators: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Investigators

• Principal Investigator: Kai-Feng Xu, M.D.; Peking Union Medical College Hosptial

• PRS Account: Peking Union Medical College Hospital
• Verification Date: September 2014