Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
completion around

Description

Summary

160 subjects with autoimmune pulmonary alveolar proteinosis (aPAP) will be randomized to receive once daily treatment with inhaled molgramostim or placebo for 48 weeks. Subjects completing the 48 week placebo-controlled period will receive open-label treatment with once daily inhaled molgramostim for 96 weeks.

Official Title

A Randomized, Double-blind, Placebo-controlled Clinical Trial of Once-daily Inhaled Molgramostim Nebulizer Solution in Adult Subjects With Autoimmune Pulmonary Alveolar Proteinosis (aPAP)

Details

This is an interventional, randomized, double-blind, 2-arm, parallel groups, placebo-controlled, multi-center, phase 3 trial in adult subjects who are diagnosed with aPAP.

An aPAP diagnosis should be confirmed by an anti-GM-CSF auto-antibody test result, and history of PAP based on either high resolution computed tomography, lung biopsy, or bronchoalveolar lavage cytology, should be available.

The trial consists of a 6-week screening period, a 48-week randomized, double-blind treatment period, a 96-week open-label treatment period, and a conditional 4-week safety follow-up period. The maximum treatment duration will be 145 weeks and the maximum trial duration will be 156 weeks. During the trial, whole lung lavage will be allowed as rescue treatment in case of worsening of aPAP.

Keywords

Autoimmune Pulmonary Alveolar Proteinosis, Pulmonary Alveolar Proteinosis, Autoimmune Diseases, Molgramostim, Sargramostim

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Subject must be ≥18 years of age, at the time of signing the informed consent (≥20 in Japan).
  2. A serum anti-GM-CSF autoantibody test result confirming autoimmune PAP.
  3. History of PAP, based on examination of a lung biopsy, bronchoalveolar lavage (BAL) cytology, or a high-resolution computed tomogram (HRCT) of the chest.
  4. DLCO 70% predicted or lower at the screening and baseline visits.
  5. Change in % predicted DLCO of <15% points during the screening period.
  6. Demonstrated functional impairment in the treadmill exercise test (defined as a peak MET ≤8).
  7. Willing and able to come off supplemental oxygen use prior to and during the treadmill exercise test, the DLCO assessment, and the arterial blood gas sampling.
  8. Resting SpO2 >85% during 15 minutes without use of supplemental oxygen at the screening visits.
  9. Male or female
  10. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    1. Male subjects: Males agreeing to use condoms during and until 30 days after last dose of trial treatment, or males having a female partner who is using adequate contraception as described below.
    2. Female subjects: Females who have been post-menopausal for >1 year, or females of childbearing potential after a confirmed menstrual period using a highly efficient method of contraception (i.e. a method with <1% failure rate such as combined hormonal contraception, progesterone-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence*), during and until 30 days after last dose of trial treatment. Females of childbearing potential must have a negative serum pregnancy test at the screening visits, and a negative urine pregnancy test at Baseline visit (Visit 3) and must not be lactating.
  11. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures specified in the protocol as judged by the Investigator.

You CAN'T join if...

  1. Diagnosis of hereditary or secondary PAP, or a metabolic disorder of surfactant production.
  2. WLL performed within 3 months prior to baseline.
  3. Requirement for WLL at screening or baseline.
  4. GM-CSF treatment within 6 months prior to baseline.
  5. Treatment with rituximab within 6 months prior to baseline.
  6. Treatment with plasmapheresis within 6 weeks prior to baseline.
  7. Treatment with any investigational medicinal product within 5 half-lives or 3 months (whichever is longer) prior to baseline.
  8. Previously randomized in this trial.
  9. History of allergic reactions to GM-CSF or any of the excipients in the nebulizer solution.
  10. Inflammatory or autoimmune disease of a severity that necessitates significant (e.g. more than 10 mg/day systemic prednisolone) immunosuppression.
  11. Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product.
  12. History of, or present, myeloproliferative disease or leukemia.
  13. Apparent pre-existing concurrent pulmonary fibrosis.
  14. Acute or unstable cardiac or pulmonary disease that may be aggravated by exercise.
  15. Known active infection (viral, bacterial, fungal, or mycobacterial) that may affect the efficacy evaluation in the trial.
  16. Physical disability or other condition that precludes safe and adequate exercise testing.
  17. Any other serious medical condition which in the opinion of the Investigator would make the subject unsuitable for the trial.
  18. Pregnant, planning to become pregnant during the trial, or breastfeeding woman. For

France only: including as further defined by French Health Code L-1121-5.

  1. For France only: Any subject considered to be "vulnerable" on account of, e.g., mental or physical disability, socio-economic situation, or subjects deprived of their liberty. For France only: including as further defined by French Health Code L1121-8-1.

Locations

  • UCLA David Geffen School of Medicine
    Los Angeles California 90095 United States
  • National Jewish Health
    Denver Colorado 80206 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Savara Inc.
ID
NCT04544293
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 160 study participants
Last Updated