Once-daily inhaled molgramostim nebulizer solution in aPAP

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Savara ApS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

10 May 2021 → ongoing

Decision date (initial)

2024-10-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Savara ApS

External identifiers

EU CT number

2024-511052-41-00

EudraCT number

2020-001263-85

ClinicalTrials.gov

NCT04544293

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacoeconomic, Therapy

Investigate the efficacy of molgramostim compared to placebo

Secondary objectives 1

1. Investigate the safety of MOL compared to placebo

Conditions and MedDRA coding

Autoimmune Pulmonary Alveolar Proteinosis

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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 first screening and Baseline visits
5. Change in % predicted DLCO of <15% points during the screening period.
6. 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.
7. Resting SpO2 >85% during 15 minutes without use of supplemental oxygen at the Screening visits.
8. Male or female
9. 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.
10. 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.
11. 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 19

1. Diagnosis of hereditary or secondary PAP, or a metabolic disorder of surfactant production.
2. Inflammatory or autoimmune disease of a severity that necessitates significant (e.g. more than 10 mg/day systemic prednisolone) immunosuppression.
3. Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product.
4. History of, or present, myeloproliferative disease or leukemia.
5. Apparent pre-existing concurrent pulmonary fibrosis, or diagnosis of interstitial lung disease other than aPAP.
6. Acute or unstable cardiac or pulmonary disease that may be aggravated by exercise or confound assessment of the primary endpoint: including presence of pulmonary edema, or diagnosis of chronic obstructive pulmonary disease (COPD), pulmonary vasculitis, or pulmonary hypertension.
7. Known active infection (viral, bacterial, fungal, or mycobacterial) that may affect the efficacy evaluation in the trial.
8. Physical disability or other condition that precludes safe and adequate exercise testing.
9. Any other serious medical condition which in the opinion of the Investigator would make the subject unsuitable for the trial
10. Pregnant, planning to become pregnant during the trial, or breastfeeding woman. For France only: including as further defined by French Health Code L-1121-5.
11. WLL performed within 3 months prior to baseline.
12. Requirement for WLL at screening or baseline.
13. GM-CSF treatment within 6 months prior to baseline.
14. Treatment with rituximab within 6 months prior to baseline.
15. Treatment with plasmapheresis within 6 weeks months prior to baseline.
16. Treatment with any investigational medicinal product within 5 half- lives or 3 months (whichever is longer) prior to baseline.
17. Previously randomized in this trial.
18. History of allergic reactions to GM-CSF or any of the excipients in the nebulizer solution.
19. For France only: Any subject considered to be “vulnerable” on account of, e.g., mental or physical disability, socio-economic situation, or subjects deprived of their liberty, including as further defined by French Health Code articles L1121-6, L1121-8, and L1121-8-1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in % predicted DLCO from baseline to Week 24

Secondary endpoints 7

1. Change in % predicted DLCO from baseline to Week 48
2. Change in SGRQ Total from baseline to Week 24
3. Change in SGRQ Activity from baseline to Week 24
4. Change in EC (expressed as peak METs) from baseline to Week 24
5. Change in SGRQ Total from baseline to Week 48
6. Change in SGRQ Activity from baseline to Week 48
7. Change in EC (expressed as peak METs) from baseline to Week 48

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Savara ApS

Sponsor organisation

Savara ApS

Address

Amaliegade 10

City

Copenhagen K

Postcode

1256

Country

Denmark

Scientific contact point

Organisation

Savara ApS

Contact name

Savara ApS

Public contact point

Organisation

Savara ApS

Contact name

Savara ApS

Third parties 4

Locations

9 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications