Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis
Condition: Autoimmune Pulmonary Alveolar Proteinosis
MeSH terms: Pulmonary Alveolar Proteinosis; Autoimmune Diseases
Intervention: Molgramostim; Placebo; PARI eFlow nebulizer system
Intervention description: 300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation; Placebo nebulizer solution for inhalation; PARI eFlow nebulizer system
Intervention MeSH terms: Molgramostim; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 139.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study evaluates inhaled molgramostim (recombinant human granulocyte macrophage-colony
      stimulating factor [rhGM-CSF]) in the treatment of autoimmune pulmonary alveolar proteinosis
      (aPAP) patients. A third of the patients will receive inhaled molgramostim once daily for 24
      weeks, a third will receive inhaled molgramostim intermittently (7 days on, 7 days off) for
      24 weeks and a third will receive inhaled matching placebo for 24 weeks.
    

Eligibility 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 2 months prior to the Baseline
             visit.

          -  Arterial oxygen tension (PaO2) <75 mmHg/<10 kilo Pascal (kPa) at rest, OR desaturation
             of >4 percentage points on the 6MWT

          -  An alveolar-arterial oxygen difference [(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 PAP

          -  WLL within 1 month of Baseline

          -  Treatment with GM-CSF within 3 months of Baseline

          -  Treatment with rituximab within 6 months of Baseline

          -  Treatment with plasmapheresis within 3 months of Baseline

          -  Treatment with any investigational medicinal product within 4 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 participant unsuitable for the trial