Autoimmune Pulmonary Alveolar ProteinosisPhase 2NCT02243228
Inhalation of Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Autoimmune Pulmonary Alveolar Proteinosis (PAP)
A Phase 2 study testing GM-CSF in people with Autoimmune Pulmonary Alveolar Proteinosis, run by Peking Union Medical College Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Pulmonary Alveolar Proteinosis
- What is being tested?
- GM-CSF
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteChina
- Study dates
- Aug 2014to Aug 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Kai-Feng Xu, M.D., 10-69155039 ext. 86, kaifeng.xu@gmail.com
Xin-Lun Tian, M.D., 10-69155039 ext. 86, xinlun_t@sina.com
About this study
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
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.
Read the 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.
- Being tested
- GM-CSF
- Keywords
- granulocyte-macrophage colony stimulating factor(GM-CSF), Autoimmune pulmonary alveolar proteinosis (PAP)
- Medical subject headings
- Pulmonary Alveolar Proteinosis, Acquired
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GM-CSFDrug
Also called HUABEI JIMUXIN
| Study group | Role | What they receive |
|---|---|---|
| GM-CSF, nebulizer | Experimental | 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. Receives: Drug: GM-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
A-aDO2 difference
Measured: 2 years
Secondary outcomes (4)
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.
Measured: up to 2 years
FEV1 difference
Measured: 2 years
6 minutes walking distance difference
Measured: 2 years
Severe adverse event
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2014 (estimated)
- Study startAug 2014
- Primary completionAug 2017 (estimated)
- Study completionAug 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autoimmune Pulmonary Alveolar ProteinosisStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kaifeng Xu, Peking Union Medical College Hospital
- Investigators
- Kai-Feng Xu, M.D., Principal investigator, Peking Union Medical College Hosptial
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02243228
- Sponsor's protocol ID
- XT 01
- Status last verified
- Sep 2014
- First submitted
- 14 Sep 2014
- Last updated
- 17 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 32615994
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02243228
- Acronym / sponsor ID
- XT 01
- Keywords
- granulocyte-macrophage colony stimulating factor(GM-CSF), Autoimmune pulmonary alveolar proteinosis (PAP)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Collaborators
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
- Study start
- Aug 2014
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 17 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GM-CSF, nebulizer | Experimental | Drug: GM-CSFAfter 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GM-CSFAlso: HUABEI JIMUXIN | Drug | GM-CSF, nebulizer |
Primary outcome
A-aDO2 difference
Time frame: 2 years
4 secondary outcomes
Time to relapse
Time frame: up to 2 years
FEV1 difference
Time frame: 2 years
6 minutes walking distance difference
Time frame: 2 years
Severe adverse event
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2014.
- Derived from this study: PubMed 32615994Tian 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.
Related trials for Autoimmune Pulmonary Alveolar Proteinosis
Active, not recruitingPhase 3
Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
Autoimmune Pulmonary Alveolar Proteinosis
Not yet recruitingPhase 2
A Study of hBMMSC Injection in Patients With aPAP
Autoimmune Pulmonary Alveolar Proteinosis
RecruitingPhase 3
Inhaled Molgramostim in Pediatric Participants With Autoimmune Pulmonary Alveolar Proteinosis (aPAP).
Autoimmune Pulmonary Alveolar Proteinosis
Not yet recruitingPhase 2
Local Spraying of GM-CSF Via Bronchoscopy in the Treatment of Autoimmune Pulmonary Alveolar Proteinosis
Pulmonary Alveolar Proteinosis
Active, not recruitingPhase 2
Study of Human Bone Marrow Mesenchymal Stem Cells in APAP
Autoimmune Pulmonary Alveolar Proteinosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kai-Feng Xu, M.D. principal investigator
Peking Union Medical College Hosptial
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GM-CSF in people with Autoimmune Pulmonary Alveolar Proteinosis, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kai-Feng Xu, M.D. (10-69155039 ext. 86, kaifeng.xu@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A-aDO2 difference (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02243228, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2014.