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

NCT01983657 | Unknown Phase 2 DMC

• 1 other identifier: 20120401
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pulmonary Alveolar Proteinosis

Keywords

Pulmonary; Pulmonary Alveolar Proteinosis; PAP

Outcome Measures

Primary Outcomes (1)

• Improvements in double pulmonary diffuse lesions （Chest CT score ）

  6 months

Secondary Outcomes (4)

• Clinical symptoms observation: shod of breath, cough (according to each score standard）

  6 months

• Granulocyte Macrophage Colony Stimulating Factor(GM-CSF) Antibody titer change

  6 months

• Improvements in pulmonary function

  6 months

• 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).

  6 months

Study Arms (4)

D1

EXPERIMENTAL

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

D2

EXPERIMENTAL

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

D3

EXPERIMENTAL

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

D4

ACTIVE COMPARATOR

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; Procedure: Whole Lung Lavage(WLL)

Interventions

rhGM-CSF DRUG

GM-CSF will be given subcutaneously according to the rule in different groups.

Also known as: TOPLEUCON, GM-CSF, Recombinant Granulocyte Macrophage-Colony Stimulating Factor, Granulocyte Macrophage-Colony Stimulating Factor

D1; D2; D3; D4

Whole Lung Lavage(WLL) PROCEDURE

using double lumen endotracheal tube (DLT) to selectively lavage one lung

Also known as: Whole Lung Lavage, WLL

D4

Eligibility Criteria

• Age: 17 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed PAP patients
• Aged 17-80
• Signed informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, 200433, China

RECRUITING

Related Publications (1)

• Zhang F, Weng D, Su Y, Yin C, Shen L, Zhang Y, Zhou Y, Li Q, Hu Y, Li H. Therapeutic effect of subcutaneous injection of low dose recombinant human granulocyte-macrophage colony-stimulating factor on pulmonary alveolar proteinosis. Respir Res. 2020 Jan 2;21(1):1. doi: 10.1186/s12931-019-1261-1.

  PMID: 31898493 DERIVED

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis

Interventions

regramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Huiping Li, Dr

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Huiping Li, Dr

CONTACT

86-13817389991; liw2013@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor,Chief of Dept. of Respiratory Medicine

Study Record Dates

• First Submitted: November 7, 2013
• First Posted: November 14, 2013
• Study Start: January 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: October 1, 2014
• Last Updated: November 18, 2013

Record last verified: 2013-11

Locations

CN (1)