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

• Register: ClinicalTrials.gov
• Last refreshed on: 24 April 2023
• Main ID: NCT02702180
• Date of registration: 28/02/2016
• Prospective Registration: Yes
• Primary sponsor: Savara Inc.
• Public title: Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis IMPALA
• Scientific title: A Randomised, Double-blind, Placebo-controlled Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis Patients
• Date of first enrolment: March 21, 2016
• Target sample size: 139
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02702180
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Australia, Denmark, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Cliff Morgan, MD
• Affiliation: Royal Brompton Hospital London

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Autoimmune Pulmonary Alveolar Proteinosis

Intervention(s)

Device: PARI eFlow nebulizer system

Drug: Molgramostim

Drug: Placebo

Primary Outcome(s)

Absolute Change From Baseline of Alveolar-arterial Oxygen Concentration (A-a(DO2)) After 24 Weeks of Treatment [Time Frame: From baseline to 24 weeks]

Secondary Outcome(s)

Number of Adverse Events (AEs) During 24 Weeks of Treatment [Time Frame: From baseline to 24 weeks]

Number of Whole Lung Lavage During 24 Weeks of Treatment [Time Frame: From baseline to 24 weeks]

Number of Participants With at Least 1 AE Leading to Treatment Discontinuation During 24 Weeks of Treatment [Time Frame: From baseline to 24 weeks]

Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score After 24 Weeks of Treatment [Time Frame: From baseline to 24 weeks]

Change From Baseline in 6-minute Walking Distance (6MWD) After 24 Weeks of Treatment [Time Frame: From baseline to 24 weeks]

Number of Serious Adverse Events (SAEs) During 24 Weeks of Treatment [Time Frame: From baseline to 24 weeks]

Number of Severe AEs During 24 Weeks of Treatment [Time Frame: From baseline to 24 weeks]

Number of Adverse Drug Reactions (ADRs) During 24 Weeks of Treatment [Time Frame: From baseline to 24 weeks]

Secondary ID(s)

2015-003878-33

MOL-PAP-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 15/04/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02702180