Phase 2
N=138
Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis
Autoimmune Pulmonary Alveolar Proteinosis
Bottom Line
View on ClinicalTrials.gov: NCT02702180 ↗Enrolled (actual)
138
Serious AEs
13.8%
Results posted
Apr 2022
Primary outcome: Primary: Absolute Change From Baseline of Alveolar-arterial Oxygen Concentration (A-a(DO2)) After 24 Weeks of Treatment — 28.6; 29.3; 32.0 mmHg — p=0.1688
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Molgramostim (Drug); Placebo (Drug); PARI eFlow nebulizer system (Device)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Savara Inc.
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Absolute Change From Baseline of Alveolar-arterial Oxygen Concentration (A-a(DO2)) After 24 Weeks of Treatment |
28.6; 29.3; 32.0 | 0.1688 |
| SECONDARY Change From Baseline in 6-minute Walking Distance (6MWD) After 24 Weeks of Treatment |
39.6; 11.3; 6.0 | 0.3159 |
| SECONDARY Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score After 24 Weeks of Treatment |
-12.3; -12.0; -4.7 | 0.0103 sig |
| SECONDARY Number of Whole Lung Lavage During 24 Weeks of Treatment |
9; 7; 17 | 0.1918 |
| SECONDARY Number of Adverse Events (AEs) During 24 Weeks of Treatment |
215; 191; 192 | — |
| SECONDARY Number of Serious Adverse Events (SAEs) During 24 Weeks of Treatment |
13; 5; 16 | — |
| SECONDARY Number of Adverse Drug Reactions (ADRs) During 24 Weeks of Treatment |
53; 27; 33 | — |
| SECONDARY Number of Severe AEs During 24 Weeks of Treatment |
28; 11; 38 | — |
| SECONDARY Number of Participants With at Least 1 AE Leading to Treatment Discontinuation During 24 Weeks of Treatment |
2; 1; 1 | — |
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) 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
Data sourced from ClinicalTrials.gov (NCT02702180). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.