A clinical trial where patients with the lung disease autoimmune Pulmonary Alveolar Proteinosis will be given the drug molgramostim nebulizer solution by inhalation.

• Register: EUCTR
• Last refreshed on: 3 December 2024
• Main ID: EUCTR2020-001263-85-RO
• Date of registration: 19/05/2022
• Prospective Registration: No
• Primary sponsor: Savara ApS
• Public title: A clinical trial where patients with the lung disease autoimmune Pulmonary Alveolar Proteinosis will be given the drug molgramostim nebulizer solution by inhalation.
• Scientific 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). - IMPALA-2
• Date of first enrolment: 11/03/2021
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-001263-85
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Germany, Greece, Ireland, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Romania, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Operations
• Affiliation: Savara ApS

• Name: Clinical Operations
• Affiliation: Savara ApS

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject must be =18 years of age, at the time of signing the informed consent. Specific for Japan; Subject must be =20 years of age, at the time of signing the informed consent.
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.
a. 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.
b. 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 Screening (Visit 1) and a negative urine pregnancy test at baseline (Visit 3) and must not be lactating.
*Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
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 months 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
MedDRA version: 21.1 Level: LLT Classification code 10037316 Term: Pulmonary alveolar proteinosis System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Molgramostim 300 µg nebulizer solution
Pharmaceutical Form: Nebulisation solution
INN or Proposed INN: Molgramostim
CAS Number: 99283-10-0
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Nebulisation solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: Investigate the efficacy of Molgramostim 300 µg nebulizer solution compared to placebo after 24-week treatment

Timepoint(s) of evaluation of this end point: Week 24

Primary end point(s): Change in % predicted DLCO from baseline to Week 24

Secondary Objective: - Investigate the safety of Molgramostim 300 µg nebulizer solution compared to placebo after 24-week treatment
- Investigate the efficacy of Molgramostim 300 µg nebulizer solution compared to placebo after 48-week treatment
- Investigate the safety of Molgramostim 300 µg nebulizer solution compared to placebo after 48-week treatment
- Investigate the efficacy of Molgramostim 300 µg nebulizer solution after 96-week treatment
- Investigate the safety of Molgramostim 300 µg nebulizer solution after 96-week treatment

Secondary Outcome(s)

Secondary end point(s): • Change in SGRQ Total from baseline to Week 24
• Change in SGRQ Activity from baseline to Week 24
• Change in EC (expressed as peak METs) from baseline to Week 24

Timepoint(s) of evaluation of this end point: Week 24

Secondary ID(s)

SAV006-05

2020-001263-85-NL

Source(s) of Monetary Support

Savara ApS

Ethics review

Status: Approved
Approval date: 11/03/2021
Contact: