Autoimmune Pulmonary Alveolar ProteinosisPhase 3IMPALA-XNCT03482752
Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis
A Phase 3 study testing Molgramostim in people with Autoimmune Pulmonary Alveolar Proteinosis, run by Savara Inc. at 13 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Pulmonary Alveolar Proteinosis
- What is being tested?
- Molgramostim
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 13 sitesin 10 countries
- Study dates
- 16 Apr 2018to 14 Jan 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
13 sites in 10 countries.
13 sites in 10 countries
Germany4 sites
Ruhrlandklinik Essen Westdeutsches Lungenzentrum am Universitätsklinikum Essen GmbH
Essen
Asklepios Fachkliniken München - Gauting Klinik für Pneumologie
Gauting
Thoraxklinik am Universitätsklinikum Heidelberg Abteilung für Pneumologie und Beatmungsmedizin
Heidelberg
Universitätsklinikum Schleswig-Holstein Zentralklinikum Lübeck Medizinische Klinik III - Pneumologie
Lübeck
Greece1 site
Attikon University Hospital 2nd Pulmonary Department Athens Medical School National and Kapodistrian University of Athens
Athens
Russia1 site
Pavlov first Saint Petersburg State Medical Univerisity
Saint Petersburg
Turkey (Türkiye)1 site
Yedikule Pulmonary Diseases and Pulmonary Surgery Training and Research Hospital
Istanbul, 34020
United Kingdom1 site
Dept. Of Intensive Care Unit Royal Brompton Hospital London
London
About this study
Official title: An Open-label, Non-controlled, Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis Patients
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.
- Being tested
- Molgramostim
- Medical subject headings
- Pulmonary Alveolar Proteinosis, Acquired
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MolgramostimDrug
Also called Recombinant human GM-CSF
300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Molgramostim |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: 139 weeks
Number of TEAEs Leading to Treatment Discontinuation
Measured: 139 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2018
- Study start16 Apr 2018
- Primary completion14 Jan 2021
- Study completion14 Jan 2021
Why it stopped: SAV006-03 was initiated before the evaluation of the IMPALA study (NCT02702180) results. Considering these results and authority advice there would not be adequate efficacy and safety data from SAV006-03 and the study was terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Autoimmune Pulmonary Alveolar ProteinosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label, non-controlled.
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Savara Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Francesco Bonella, Prof., Principal investigator, Interstitial and Rare Lung Disease Unit, Ruhrlandklinik University Hospital, Essen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03482752
- Sponsor's protocol ID
- SAV006-03
- Other IDs
- 2017-004078-32, 2017
- Acronym
- IMPALA-X
- Status last verified
- Jan 2024
- First submitted
- 21 Mar 2018
- Last updated
- 3 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-controlled, Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis Patients
- ClinicalTrials.gov ID
- NCT03482752
- Acronym / sponsor ID
- IMPALA-X / SAV006-03
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: SAV006-03 was initiated before the evaluation of the IMPALA study (NCT02702180) results. Considering these results and authority advice there would not be adequate efficacy and safety data from SAV006-03 and the study was terminated.
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Savara Inc.Industry (pharma, biotech, devices)
- Study start
- 16 Apr 2018 (actual)
- Primary completion
- 14 Jan 2021 (actual)
- Study completion
- 14 Jan 2021 (actual)
- First posted
- 29 Mar 2018 (actual)
- Results
- Posted 3 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label, non-controlled.
| Arm | Type | Receives |
|---|---|---|
| Molgramostim nebulizer solution (300 μg) | Experimental | Drug: MolgramostimOpen-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MolgramostimAlso: Recombinant human GM-CSF300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment. | Drug | Molgramostim nebulizer solution (300 μg) |
Primary outcome
Number of Treatment-emergent Adverse Events (TEAEs)
Time frame: 139 weeks
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.
Number of Serious TEAEs
Time frame: 139 weeks
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).
Number of Treatment-emergent Adverse Drug Reactions (ADRs)
Time frame: 139 weeks
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.
Number of TEAEs Leading to Treatment Discontinuation
Time frame: 139 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Bonella, Prof. principal investigator
Interstitial and Rare Lung Disease Unit, Ruhrlandklinik University Hospital, Essen, Germany
13 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Molgramostim in people with Autoimmune Pulmonary Alveolar Proteinosis, run by Savara Inc. at 13 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany, Denmark, France, Greece, Israel and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Treatment-emergent Adverse Events (TEAEs) (time frame: 139 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.