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

Primary Purpose

Autoimmune Pulmonary Alveolar Proteinosis

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

GM-CSF

About this trial

This is an interventional treatment trial for Autoimmune Pulmonary Alveolar Proteinosis focused on measuring granulocyte-macrophage colony stimulating factor(GM-CSF), Autoimmune pulmonary alveolar proteinosis (PAP)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GM-CSF, nebulizer

Arm Description

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.

Outcomes

Primary Outcome Measures

A-aDO2 difference

Secondary Outcome Measures

Time to relapse

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

6 minutes walking distance difference

Severe adverse event

Full Information

NCT ID

NCT02243228

First Posted

September 14, 2014

Last Updated

September 16, 2014

Sponsor

Peking Union Medical College Hospital

Collaborators

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

1. Study Identification

Unique Protocol Identification Number

NCT02243228

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2014

Overall Recruitment Status

Unknown status

Study Start Date

August 2014 (undefined)

Primary Completion Date

August 2017 (Anticipated)

Study Completion Date

August 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking Union Medical College Hospital

Collaborators

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autoimmune Pulmonary Alveolar Proteinosis

Keywords

granulocyte-macrophage colony stimulating factor(GM-CSF), Autoimmune pulmonary alveolar proteinosis (PAP)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GM-CSF, nebulizer

Arm Type

Experimental

Arm Description

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 Type

Drug

Intervention Name(s)

GM-CSF

Other Intervention Name(s)

HUABEI JIMUXIN

Primary Outcome Measure Information:

Title

A-aDO2 difference

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Time to relapse

Description

Time Frame

up to 2 years

Title

FEV1 difference

Time Frame

2 years

Title

6 minutes walking distance difference

Time Frame

2 years

Title

Severe adverse event

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Kai-Feng Xu, M.D.

Phone

10-69155039

Ext

kaifeng.xu@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Xin-Lun Tian, M.D.

Phone

10-69155039

Ext

xinlun_t@sina.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kai-Feng Xu, M.D.

Organizational Affiliation

Peking Union Medical College Hosptial

Official's Role

Principal Investigator

Facility Information:

Facility Name

Peking Union Medical College Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100730

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kai-Feng Xu, M.D.

Phone

10-69155039

Ext

kaifeng.xu@gmail.com

First Name & Middle Initial & Last Name & Degree

Xin-Lun Tian, M.D.

Phone

10-69155039

Ext

xinlun_t@sina.com

First Name & Middle Initial & Last Name & Degree

Xin-Lun Tian, M.D.

12. IPD Sharing Statement

Citations:

PubMed Identifier

32615994

Citation

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.

Results Reference

derived

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

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