Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis

NCT03482752 | Terminated Phase 3 Results

• 2 other identifiers: SAV006-032017-004078-32
• Study Type: interventional
• Target: 60
• Locations: 10 countries
• Sites: 13

Brief Summary

SAV006-03 is an open-label extension study for participants who had completed the IMPALA study. At the baseline visit, eligible participants may continue or re-start treatment with 300 µg inhaled molgramostim (recombinant human Granulocyte-Macrophage Colony Stimulating Factor; GM-CSF) administered intermittently in cycles of seven days molgramostim, administered once daily, and seven days off treatment. Participants will be treated with inhaled molgramostim for up to 36 months. During the trial, whole lung lavage will be applied as rescue therapy.

Conditions

Autoimmune Pulmonary Alveolar Proteinosis

Outcome Measures

Primary Outcomes (4)

• Number of Treatment-emergent Adverse Events (TEAEs)

  The primary objective of this trial was safety assessed by adverse event (AE) reporting. Definitions and reporting procedures for AEs were done according to current regulatory standards. AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns. Treatment-emergent was defined as events occurring on study drug and up to 7 days after last dose of study drug.

  139 weeks

• Number of Serious TEAEs

  Serious TEAEs were defined as any untoward medicinal occurrence or effect that at any dose: * Results in death * Is life-threatening * Requires hospitalisation or prolongation of existing hospitalisation * Results in persistent or significant disability or incapacity * Is a congenital abnormality or birth defect * May jeopardise the participant or may require medical intervention to prevent one or more of the outcomes listed above (Important Medical Events).

  139 weeks

• Number of Treatment-emergent Adverse Drug Reactions (ADRs)

  All AEs were assessed by the investigator for causality (unlikely, possible, probable, not applicable) according to current regulatory standards. AEs which had a 'possible' or 'probable' causality were classified as ADRs.

  139 weeks

• Number of TEAEs Leading to Treatment Discontinuation

  139 weeks

Study Arms (1)

Molgramostim nebulizer solution (300 μg)

EXPERIMENTAL

Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment).

Drug: Molgramostim

Interventions

Molgramostim DRUG

300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.

Also known as: Recombinant human GM-CSF

Molgramostim nebulizer solution (300 μg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Completer of the IMPALA trial.
• Females who have been post menopausal for \>1 year, or females of child-bearing potential who are not pregnant or lactating and are using acceptable contraceptive methods.
• Males agreeing to use using acceptable contraceptive methods.
• Willing and able to provide signed informed consent.

You may not qualify if:

• Treatment with GM-CSF products other than molgramostim nebuliser solution within three months of Baseline.
• Treatment with any investigational medicinal product other than inhaled molgramostim within four weeks of Baseline.
• 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.
• Apparent pre-existing concurrent pulmonary fibrosis.
• Any other serious medical condition which in the opinion of the investigator would make the subject unsuitable for the trial.

Sponsors & Collaborators

• Savara Inc.: lead

Study Sites (13)

Dept. Of Respiratory Diseases & Allergy

Aarhus, Denmark

Location

CHU Rennes Hospital Pontchaillou, Service de Pneumologie

Rennes, France

Location

Ruhrlandklinik Essen Westdeutsches Lungenzentrum am Universitätsklinikum Essen GmbH

Essen, Germany

Location

Asklepios Fachkliniken München - Gauting Klinik für Pneumologie

Gauting, Germany

Location

Thoraxklinik am Universitätsklinikum Heidelberg Abteilung für Pneumologie und Beatmungsmedizin

Heidelberg, Germany

Location

Universitätsklinikum Schleswig-Holstein Zentralklinikum Lübeck Medizinische Klinik III - Pneumologie

Lübeck, Germany

Location

Attikon University Hospital 2nd Pulmonary Department Athens Medical School National and Kapodistrian University of Athens

Athens, Greece

Location

Rabin Medical Center Institute of Pulomonary Medicine

Tel Aviv, Israel

Location

S.C. Pneumologia Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

Location

St. Antonius Hospital

Nieuwegein, Netherlands

Location

Pavlov first Saint Petersburg State Medical Univerisity

Saint Petersburg, Russia

Location

Yedikule Pulmonary Diseases and Pulmonary Surgery Training and Research Hospital

Istanbul, 34020, Turkey (Türkiye)

Location

Dept. Of Intensive Care Unit Royal Brompton Hospital London

London, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis, Acquired

Interventions

molgramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

No hypothesis/statistical testing was planned for any of the endpoints of this study but only descriptive statistics were to be used. Efficacy endpoints were secondary endpoints. Due to early study termination, only limited efficacy data were available for evaluation and in general, no firm conclusion based on efficacy data are applicable. No deaths occurred during the study but 1 participant died due to COVID-19 24 days after last dose, i.e. outside the definition of 'treatment-emergent'.

Results Point of Contact

• Title: Raymond D Pratt, Chief Medical Officer
• Organization: Savara Inc

ray.pratt@savarapharma.com

+1 512 784 8757

Study Officials

• Francesco Bonella, Prof.

  Interstitial and Rare Lung Disease Unit, Ruhrlandklinik University Hospital, Essen, Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, non-controlled.

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: March 29, 2018
• Study Start: April 16, 2018
• Primary Completion: January 14, 2021
• Study Completion: January 14, 2021
• Last Updated: July 3, 2024
• Results First Posted: July 3, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); IL (1); RU (1); NL (1); GR (1); TU (1); IT (1); GB (1); FR (1); DE (4)