search
Back to results

Pulmonary Alveolar Proteinosis GM-CSF Inhalation Efficacy Trial in Japan

Primary Purpose

Pulmonary Alveolar Proteinosis, Autoimmune

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Sargramostim
Placebo
Sponsored by
Niigata University Medical & Dental Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Alveolar Proteinosis, Autoimmune

Eligibility Criteria

16 Years - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age over 16 years and below 80 years (as of the date of registration).
  2. Can provide signed informed consent.
  3. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures specified in the protocol (including short-term hospital admission).
  4. Autoimmune pulmonary alveolar proteinosis diagnosed by both HR-CT and biopsy and/or BAL as well as GM-CSF antibodies in serum positive.
  5. PaO2 < 70 mmHg after 5 minutes spine position at room air, or PaO2 < 75 mmHg after 5 minutes spine position at room air and with symptom(s) including cough, sputum and exertional dyspnea

Exclusion Criteria:

  1. Diagnosed as secondary or hereditary pulmonary alveolar proteinosis
  2. WBC of 12,000/mm3 or more
  3. Fever of 38 degree celsius or more
  4. Severe edema
  5. History of malignant disease within recent 5 years (not applied to the treated cases of uterine carcinoma in situ and local basal cell carcinoma)
  6. Complication of cardiovascular diseases including congestive heart failure, angina pectoris, hemorrhagic tendency, etc with severe condition.
  7. Complication of respiratory diseases such as pulmonary infectious disease(incl. pulmonary tuberculosis), bronchial asthma, lung fibrosis ,interstitial pneumonitis, or bronchiectasis, in which the evaluations of safety and efficacy of GM-CSF therapy are considered as difficult.
  8. History or complication of infectious diseases which require systemic administration of antibiotics, antifungal or antiviral agents within recent 2 weeks.
  9. Treatment with other cytokines
  10. Pregnant or possibly pregnant women, lactating women, and women who desire to become pregnant during the study period
  11. Patients who have been treated with whole-lung lavage, repeated segmental-lung lavage, or rituximab within 6 months before the start of the study (this criterion does not apply to patients for whom 6 months or more have elapsed after their last lavage or rituximab)
  12. Severe liver dysfunction (AST > 100 IU/L and/or ALT > 100 IU/L and/or T-bil >3.0mg/dL)
  13. Severe renal dysfunction (Ccr < 30 mL/min, calculated by Cockcroft-Gault (CG) formula)
  14. Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product
  15. Treatment with oral or intravenous administration or inhalation of corticosteroids.
  16. Treatment with other inhaled drugs.
  17. Previously treated with GM-CSF before the start of the study.
  18. Demonstrate hypersensitivity to GM-CSF agent.
  19. Other patients judged to be inappropriate for the study by the attending physician (e.g., patients who are unlikely to complete treatment or are uncooperative).

Sites / Locations

  • Niigata University Med & Dental Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Group1

Group2

Arm Description

Treatments for Group 1 include GM-CSF inhalation with 250 mcg/day/body of sargramostim (125 mcg BID on Days 1-7, none on Days 8-14) for twelve 2-week cycles.

Treatments for Group 2 include placebo inhalation (Placebo BID on Days 1-7, none on Days 8-14) for twelve 2-week cycles.

Outcomes

Primary Outcome Measures

Change value of AaDO2 between baseline and 24 weeks

Secondary Outcome Measures

Full Information

First Posted
July 13, 2016
Last Updated
February 6, 2019
Sponsor
Niigata University Medical & Dental Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT02835742
Brief Title
Pulmonary Alveolar Proteinosis GM-CSF Inhalation Efficacy Trial in Japan
Official Title
Pulmonary Alveolar Proteinosis GM-CSF Inhalation Efficacy Trial in Japan
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
September 1, 2016 (Actual)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Niigata University Medical & Dental Hospital

4. Oversight

5. Study Description

Brief Summary
Objective: Determine the safety and efficacy of GM-CSF inhalation in patients with aPAP. Study Design: multi-center, randomized, double-blind, placebo- controlled, safety/efficacy study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Alveolar Proteinosis, Autoimmune

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
78 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group1
Arm Type
Active Comparator
Arm Description
Treatments for Group 1 include GM-CSF inhalation with 250 mcg/day/body of sargramostim (125 mcg BID on Days 1-7, none on Days 8-14) for twelve 2-week cycles.
Arm Title
Group2
Arm Type
Placebo Comparator
Arm Description
Treatments for Group 2 include placebo inhalation (Placebo BID on Days 1-7, none on Days 8-14) for twelve 2-week cycles.
Intervention Type
Drug
Intervention Name(s)
Sargramostim
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change value of AaDO2 between baseline and 24 weeks
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age over 16 years and below 80 years (as of the date of registration). Can provide signed informed consent. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures specified in the protocol (including short-term hospital admission). Autoimmune pulmonary alveolar proteinosis diagnosed by both HR-CT and biopsy and/or BAL as well as GM-CSF antibodies in serum positive. PaO2 < 70 mmHg after 5 minutes spine position at room air, or PaO2 < 75 mmHg after 5 minutes spine position at room air and with symptom(s) including cough, sputum and exertional dyspnea Exclusion Criteria: Diagnosed as secondary or hereditary pulmonary alveolar proteinosis WBC of 12,000/mm3 or more Fever of 38 degree celsius or more Severe edema History of malignant disease within recent 5 years (not applied to the treated cases of uterine carcinoma in situ and local basal cell carcinoma) Complication of cardiovascular diseases including congestive heart failure, angina pectoris, hemorrhagic tendency, etc with severe condition. Complication of respiratory diseases such as pulmonary infectious disease(incl. pulmonary tuberculosis), bronchial asthma, lung fibrosis ,interstitial pneumonitis, or bronchiectasis, in which the evaluations of safety and efficacy of GM-CSF therapy are considered as difficult. History or complication of infectious diseases which require systemic administration of antibiotics, antifungal or antiviral agents within recent 2 weeks. Treatment with other cytokines Pregnant or possibly pregnant women, lactating women, and women who desire to become pregnant during the study period Patients who have been treated with whole-lung lavage, repeated segmental-lung lavage, or rituximab within 6 months before the start of the study (this criterion does not apply to patients for whom 6 months or more have elapsed after their last lavage or rituximab) Severe liver dysfunction (AST > 100 IU/L and/or ALT > 100 IU/L and/or T-bil >3.0mg/dL) Severe renal dysfunction (Ccr < 30 mL/min, calculated by Cockcroft-Gault (CG) formula) Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product Treatment with oral or intravenous administration or inhalation of corticosteroids. Treatment with other inhaled drugs. Previously treated with GM-CSF before the start of the study. Demonstrate hypersensitivity to GM-CSF agent. Other patients judged to be inappropriate for the study by the attending physician (e.g., patients who are unlikely to complete treatment or are uncooperative).
Facility Information:
Facility Name
Niigata University Med & Dental Hospital
City
Niigata
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
31483963
Citation
Tazawa R, Ueda T, Abe M, Tatsumi K, Eda R, Kondoh S, Morimoto K, Tanaka T, Yamaguchi E, Takahashi A, Oda M, Ishii H, Izumi S, Sugiyama H, Nakagawa A, Tomii K, Suzuki M, Konno S, Ohkouchi S, Tode N, Handa T, Hirai T, Inoue Y, Arai T, Asakawa K, Sakagami T, Hashimoto A, Tanaka T, Takada T, Mikami A, Kitamura N, Nakata K. Inhaled GM-CSF for Pulmonary Alveolar Proteinosis. N Engl J Med. 2019 Sep 5;381(10):923-932. doi: 10.1056/NEJMoa1816216.
Results Reference
derived

Learn more about this trial

Pulmonary Alveolar Proteinosis GM-CSF Inhalation Efficacy Trial in Japan

We'll reach out to this number within 24 hrs