Pulmonary Alveolar Proteinosis GM-CSF Inhalation Efficacy Trial in Japan

NCT ID: NCT02835742

Last Updated: 2019-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-01
• Study Completion Date: 2018-06-30

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.

Conditions

Pulmonary Alveolar Proteinosis, Autoimmune

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group1

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.

Group Type: ACTIVE_COMPARATOR

Sargramostim

Intervention Type: DRUG

Group2

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Sargramostim

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Niigata University Medical & Dental Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Niigata University Med & Dental Hospital

Niigata, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 31483963 (View on PubMed)

Other Identifiers

PAGE

Identifier Type: -

Identifier Source: org_study_id