Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)

• Status: Completed
• Trial end date: 2019-09-27
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluates inhaled molgramostim (recombinant human (rh) Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)) in the treatment of autoimmune pulmonary alveolar proteinosis patients. A third of the patients will receive inhaled molgramostim daily for 24 weeks, a third will receive inhaled molgramostim intermittently (seven days on, seven days off) for 24 weeks and a third will receive inhaled matching placebo for 24 weeks.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Savara Inc.
• Treatments: Molgramostim; Pharmaceutical Solutions; Sargramostim

Criteria

Inclusion Criteria:

• aPAP diagnosed by computed tomography, or by biopsy, or by Broncho Alveolar Lavage (BAL), and by increased GM-CSF autoantibodies in serum.

• Stable or progressive aPAP during a minimum period of two months prior to the Baseline visit.

• Arterial oxygen concentration <75 mmHg/<10 kilo Pascal (kPa) at rest, OR desaturation of >4 percentage points on the 6 Minute Walk Test (6MWT)

• An (A-a)DO2 of minimum 25 mmHg/3.33 kPa

• Female or male ≥18 years of age

• 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, vasectomised partner, sexual abstinence), during and until 30 days after last dose of double-blind trial treatment. Females of childbearing potential must have a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at dosing at Baseline (Visit 2) and must not be lactating

• Males agreeing to use condoms during and until 30 days after last dose of double-blind medication, or males having a female partner who is using adequate contraception as described above

• Willing and able to provide signed informed consent

• 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

Exclusion Criteria:

• Diagnosis of hereditary or secondary pulmonary alveolar proteinosis (PAP)

• WLL within one month of Baseline

• Treatment with GM-CSF within three months of Baseline

• Treatment with rituximab within six months of Baseline

• Treatment with plasmapheresis within three months of Baseline

• Treatment with any investigational medicinal product within four weeks of Screening

• Concomitant use of sputum modifying drugs such as carbocysteine or ambroxol

• History of allergic reactions to GM-CSF

• Connective tissue disease, inflammatory bowel disease or other autoimmune disorder requiring treatment associated with significant immunosuppression, e.g. more than 10 mg/day systemic prednisolone

• Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product

• History of, or present, myeloproliferative disease or leukaemia

• Known active infection (viral, bacterial, fungal or mycobacterial)

• Apparent pre-existing concurrent pulmonary fibrosis

• Any other serious medical condition which in the opinion of the investigator would make the subject unsuitable for the trial