NCT02835742

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Sep 2016

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 13, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 18, 2016

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2016

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2018

Completed
Last Updated

February 7, 2019

Status Verified

February 1, 2019

Enrollment Period

11 months

First QC Date

July 13, 2016

Last Update Submit

February 6, 2019

Conditions

Pulmonary Alveolar Proteinosis, Autoimmune

Outcome Measures

Primary Outcomes (1)

  • Change value of AaDO2 between baseline and 24 weeks

    24 weeks

Study Arms (2)

Group1

ACTIVE COMPARATOR

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.

Drug: Sargramostim

Group2

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

SargramostimDRUG
Group1
PlaceboDRUG
Group2

Eligibility Criteria

Age16 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Niigata University Med & Dental Hospital

Niigata, Japan

Location

Related Publications (1)

  • 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.

    PMID: 31483963DERIVED

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis, Acquired

Interventions

sargramostim

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 13, 2016

First Posted

July 18, 2016

Study Start

September 1, 2016

Primary Completion

August 1, 2017

Study Completion

June 1, 2018

Last Updated

February 7, 2019

Record last verified: 2019-02

Locations

JP(1)