Study of Subcutaneous Injection of Low-dose rhGM-CSF +/- WLL in PAP. - Full Text View

Purpose

The purpose of this study is to establish an efficient and economic treatment scheme by evaluation of the safety and efficacy of subcutaneous injection of low-dose rhGM-CSF, or of similar injection after whole lung lavage , in patients with PAP.

Condition	Intervention	Phase
Pulmonary Alveolar Proteinosis	Drug: rhGM-CSF Procedure: Whole Lung Lavage(WLL)	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Study of Subcutaneous Injection of Low-dose Recombinant Granulocyte Macrophage-Colony Stimulating Factor (rhGM-CSF) +/- Whole Lung Lavage(WLL) in Pulmonary Alveolar Proteinosis.

Further study details as provided by Shanghai Pulmonary Hospital, Shanghai, China:

Primary Outcome Measures:

Improvements in double pulmonary diffuse lesions （Chest CT score ） [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical symptoms observation: shod of breath, cough (according to each score standard） [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Granulocyte Macrophage Colony Stimulating Factor(GM-CSF) Antibody titer change [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Improvements in pulmonary function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Pulmonary function tests include residual volume/total lung capacity(RV/TLC), forced vital capacity(FVC), forced expiratory volume in one second/forced vital capacity(FEV1/FVC), diffusing capacity of carbon monoxide(DLCO).
Improvements in arterial blood gas, including alveolar-arterial oxygen difference(A-aDO2), partial pressure of oxygen(PaO2), partial pressure of carbon dioxide in artery(PaCO2), arterial oxygen saturation(SaO2). [ Time Frame: 6 months ] [ Designated as safety issue: No ]


Estimated Enrollment:	40
Study Start Date:	January 2012
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: D1 Patients diagnosed with PAP will be received rhGM-CSF 1.25 ug/kg/d subcutaneously for 1 month, before evaluation on the 30th day (±3 day). If the treatment is effective, participants may be entered into low-dose group(D1)(rhGM-CSF administration 1.25 ug/kg/d, qd, sc, for 2 months，then rhGM-CSF administration 1.25 ug/kg/d, qod, sc, for 3 months), when the chest CT absorption≥25% , and /or the PaO2 elevated by 5 mm Hg.	Drug: rhGM-CSF GM-CSF will be given subcutaneously according to the rule in different groups. Other Names: TOPLEUCON GM-CSF Recombinant Granulocyte Macrophage-Colony Stimulating Factor Granulocyte Macrophage-Colony Stimulating Factor
Experimental: D2 Patients diagnosed with PAP will be received rhGM-CSF 1.25 ug/kg/d subcutaneously for 1 month, before evaluation on the 30th day (±3 day). When the treatment is ineffective, and anti-GM-CSF antibody titers level ≥1:1000，the dose will be increased to 2.5 ug/kg/d. After 2 months, if the clinical response was optimal, that dose is continued for 3 months, and defined as group 2(D2).	Drug: rhGM-CSF GM-CSF will be given subcutaneously according to the rule in different groups. Other Names: TOPLEUCON GM-CSF Recombinant Granulocyte Macrophage-Colony Stimulating Factor Granulocyte Macrophage-Colony Stimulating Factor
Experimental: D3 Patients diagnosed with PAP will be received rhGM-CSF 1.25 ug/kg/d subcutaneously for 1 month, before evaluation on the 30th day (±3 day). When the treatment is ineffective, and anti-GM-CSF antibody titers level ≥1:1000，the dose will be increased to 2.5 ug/kg/d. After 2 months, if the clinical response was not optimal, the patients will receive whole lung lavage(WLL), who are defined as group 3(D3).	Drug: rhGM-CSF GM-CSF will be given subcutaneously according to the rule in different groups. Other Names: TOPLEUCON GM-CSF Recombinant Granulocyte Macrophage-Colony Stimulating Factor Granulocyte Macrophage-Colony Stimulating Factor
Active Comparator: D4 Patients diagnosed with PAP will be received rhGM-CSF 1.25 ug/kg/d subcutaneously for 1 month, before evaluation on the 30th day (±3 day). When the treatment is ineffective, and anti-GM-CSF antibody titers level ＜1:1000，the patients will receive whole lung lavage(WLL), then give rhGM-CSF administration (1.25 ug/kg/d) for 3 months, which belong to group4(D4).	Drug: rhGM-CSF GM-CSF will be given subcutaneously according to the rule in different groups. Other Names: TOPLEUCON GM-CSF Recombinant Granulocyte Macrophage-Colony Stimulating Factor Granulocyte Macrophage-Colony Stimulating Factor Procedure: Whole Lung Lavage(WLL) using double lumen endotracheal tube (DLT) to selectively lavage one lung Other Names: Whole Lung Lavage WLL

Detailed Description:

The purpose of this study is to establish an efficient and economic treatment scheme by evaluation of the safety and efficacy of subcutaneous injection of low-dose rhGM-CSF, or of similar injection after whole lung lavage , in patients with PAP. During the observation, study visits will occur at the end of each month. During the 1-year follow-up period which is lasting 6 months after the treatment, all participants will be required to check the various efficacy indicators.

Eligibility


Ages Eligible for Study:	17 Years to 80 Years (Child, Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosed PAP patients
Aged 17-80
Signed informed consent

Exclusion Criteria:

Secondary PAP
Received whole lung lavage therapy within 4 weeks before enrollment
Received previous GM-CSF therapy within 6 months before enrollment
WBC≥12,000/ul
fever≥38℃
Severe edema, severe liver, kidney, lung and cardiovascular disease.
Pregnant，planning to get pregnant or nursing
Inability to express the subjective discomfort
Serious drug allergy history, E.coli preparation or rhGM-CSF serious allergy history

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01983657

Contacts


Contact: Huiping Li, Dr	86-13817389991	liw2013@126.com

Locations


China
Shanghai Pulmonary Hospital	Recruiting
Shanghai, China, 200433
Contact: Huiping Li, Doctor 86-13817389991 liw2013@126.com
Principal Investigator: Huiping Li, Doctor

Sponsors and Collaborators

Shanghai Pulmonary Hospital, Shanghai, China

Investigators


Principal Investigator:	Huiping Li, Dr	Shanghai Pulmonary Hospital, Shanghai, China

More Information


Responsible Party:	Huiping Li, Professor,Chief of Dept. of Respiratory Medicine, Shanghai Pulmonary Hospital, Shanghai, China
ClinicalTrials.gov Identifier:	NCT01983657 History of Changes
Other Study ID Numbers:	20120401
Study First Received:	November 7, 2013
Last Updated:	November 14, 2013
Health Authority:	China: Food and Drug Administration

Keywords provided by Shanghai Pulmonary Hospital, Shanghai, China:


Pulmonary Pulmonary Alveolar Proteinosis PAP

Additional relevant MeSH terms:


Pulmonary Alveolar Proteinosis Lung Diseases Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 27, 2016

Study of Subcutaneous Injection of Low-dose rhGM-CSF +/- WLL in PAP. (PAP)