Pulmonary Alveolar ProteinosisPhase 1NCT02468908
Inhaled Molgramostim (rhGM-CSF) in Healthy Adult Subjects
A Phase 1 study testing Molgramostim in people with Pulmonary Alveolar Proteinosis and Bronchiectasis, run by Savara Inc. at 1 site in United Kingdom.
Trial summary
This is a randomized, double-blind, placebo-controlled, single ascending (SAD), and multiple ascending dose (MAD) study conducted at a single clinical site within the UK. Healthy male and female subjects (on non-child bearing potential) will be enrolled to investigate single inhaled doses of molgramostim at 3 dose… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Alveolar Proteinosis, Bronchiectasis, Cystic Fibrosis
- What is being tested?
- Molgramostim
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2015to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy, adult, male or female, 18- 55 years of age, inclusive, at screening.
- Life-long non smoker who has not used nicotine containing products.
- Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening.
- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, spirometry, vital signs, or ECGs, as deemed by the PI.
- Females must be of non-child bearing potential who must have undergone one of the following sterilization procedures at least 6 months prior to dosing in Part 1 or prior to the first dose in Part 2:
- hysteroscopic sterilization;
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- bilateral tubal ligation or bilateral salpingectomy;
- hysterectomy;
- bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to dosing in Part 1 or prior to the first dose in Part 2, and FSH serum levels consistent with postmenopausal status as per PI's judgment.
- A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study medication. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to study start. A male who has been vasectomized less than 4 months prior to study start must follow the same restrictions as a non vasectomized male).
- If male must agree not to donate sperm from dosing in Part 1 or from the first dose in Part 2, until 90 days following last dose.
- Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.
Who cannot join
- Subject is mentally or legally incapacitated or has significant emotional problems at the time of screening visit or expected during the conduct of the study.
- History or presence of clinically significant medical condition(s) (including ongoing active infections) or psychiatric condition(s) or disease(s) in the opinion of the PI.
- History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- Abnormal spirometry test results, in the opinion of the PI.
- History of severe or unexplained adverse reactions during aerosol delivery of any medicinal product.
- History or presence of alcoholism or drug abuse within the past 2 years prior to screening.
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- History or presence of hypersensitivity or idiosyncratic reaction to molgramostim or to related compounds (i.e., Growgen®, Leucomax®, Leukine®, Topleucon™).
- Clinically significant history or presence of ECG abnormalities such as second- or third degree atrioventricular block, evidence, or family history of prolonged QT syndrome.
- Allergy to bandaids, adhesive dressing, or medical tape.
- Positive urine drug at screening or check in.
- Positive alcohol test at check-in.
- Drink alcohol in excess of 21 units per week for males or 14 units per week for females, with one unit = 150 mL of wine or 360 mL of beer or 45 mL of 45% alcohol.
- Positive urine cotinine at screening and check-in.
- Positive results at screening for HIV, HBsAg, or HCV.
- Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
- Seated heart rate is lower than 45 bpm or higher than 99 bpm at screening.
- QTcF interval is >430 msec (males) or >450 msec (females) at screening or deemed clinically abnormal by the PI.
- Unable to refrain from or anticipates the use of:
- Any drug, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to dosing in Part 1 or prior to the first dose in Part 2, and throughout the study. Hormone replacement therapy (HRT) is not permitted in this study and within 3 months prior to screening. During the study paracetamol (up to 2 g per 24 hours) may be administered at the discretion of the PI.
- Any drugs known to be significant inducers of CYP enzymes and/or P gp, including St. John's Wort, for 28 days prior to dosing in Part 1 or prior to the first dose in Part 2, and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of PK/PD interaction with study drug.
- Have been on a diet incompatible with the on study diet, in the opinion of the PI, within the 28 days prior to the first dose of study drug, and throughout the study.
- Haemoglobin or total WBC outside the normal range at screening.
- Donation of blood or plasma within 90 days prior to dosing in Part 1 or prior to the first dose in Part 2.
- Donation of bone marrow within the last 6 months prior to dosing in Part 1 or prior to the first dose in Part 2.
- Participation in another clinical trial within 90 days prior to dosing in Part 1 or prior to the first dose in Part 2.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Single-Centre, Single Ascending Dose and Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Molgramostim When Administered by Inhalation to Healthy Adult Subjects
This is a randomized, double-blind, placebo-controlled, single ascending (SAD), and multiple ascending dose (MAD) study conducted at a single clinical site within the UK. Healthy male and female subjects (on non-child bearing potential) will be enrolled to investigate single inhaled doses of molgramostim at 3 dose levels (Part 1) and multiple inhaled doses at 2 dose levels (Part 2). The 2 doses in the multiple ascending dose regimens will be administered once daily (QD) for 6 consecutive days. The clinical indication for inhaled molgramostim is the treatment of respiratory diseases such as aPAP, bronchiectasis and cystic fibrosis. The Clinical trial will involve 42 healthy participants. The trial is expected to last approximately 4 months.
- Conditions
- Pulmonary Alveolar Proteinosis, Bronchiectasis, Cystic Fibrosis, Acute Respiratory Distress Syndrome
- Being tested
- Molgramostim, Placebo
- Medical subject headings
- Pulmonary Alveolar Proteinosis, Bronchiectasis, Cystic Fibrosis, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MolgramostimDrug
Also called Granulocyte Macrophage-Colony Stimulating Factor (rhGM-CSF)
PlaceboDrug
Also called Nebuliser solution
| Study group | Role | What they receive |
|---|---|---|
| Molgramostim nebuliser solution, inhaled | Experimental | Single dose 150, 300 and 600 ug, multiple dose 300 and 600 ug for 6 days Receives: Drug: Molgramostim |
| Nebuliser solution, inhaled | Placebo comparator | Inhaled nebuliser solution Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and severity of treatment-emergent Adverse Events (AEs) following single and multiple inhaled doses of molgramostim
Measured: 1-6 days
Secondary outcomes (2)
PK parameters: Area under the plasma concentration time curve (AUC), Peak Peak Plasma concentration - Cmax, Time to reach maximum observed serum concentration - tmax
Measured: 1-6 days
PK parameters: Apparent terminal elimination rate constant - k(el) and Apparent terminal elimination rate constant - t(1/2)
Measured: 1-6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study startMay 2015
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Savara Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Celerion
- Responsible party
- Sponsor
- Investigators
- Johnston Steward, MD, Principal investigator, Celerion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02468908
- Sponsor's protocol ID
- MOL-001
- Status last verified
- Nov 2015
- First submitted
- 3 Jun 2015
- Last updated
- 23 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Trapnell BC, Carey BC, Robinson BR. Pharmacokinetics and pharmacodynamics of inhaled molgramostim in healthy people. BMJ Open Respir Res. 2025 Sep 18;12(1):e002832. doi: 10.1136/bmjresp-2024-002832.
PubMed 40973220
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Single-Centre, Single Ascending Dose and Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Molgramostim When Administered by Inhalation to Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT02468908
- Acronym / sponsor ID
- MOL-001
- Conditions
- Pulmonary Alveolar Proteinosis, Bronchiectasis, Cystic Fibrosis, Acute Respiratory Distress Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Savara Inc.Industry (pharma, biotech, devices)
- Collaborators
- Celerion
- Study start
- May 2015
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 11 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double-blind, placebo-controlled, single ascending (SAD), and multiple ascending dose (MAD) study conducted at a single clinical site within the UK. Healthy male and female subjects (on non-child bearing potential) will be enrolled to investigate single inhaled doses of molgramostim at 3 dose levels (Part 1) and multiple inhaled doses at 2 dose levels (Part 2). The 2 doses in the multiple ascending dose regimens will be administered once daily (QD) for 6 consecutive days. The clinical indication for inhaled molgramostim is the treatment of respiratory diseases such as aPAP, bronchiectasis and cystic fibrosis. The Clinical trial will involve 42 healthy participants. The trial is expected to last approximately 4 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Molgramostim nebuliser solution, inhaled | Experimental | Drug: MolgramostimSingle dose 150, 300 and 600 ug, multiple dose 300 and 600 ug for 6 days |
| Nebuliser solution, inhaled | Placebo comparator | Drug: PlaceboInhaled nebuliser solution |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Healthy, adult, male or female, 18- 55 years of age, inclusive, at screening.
- Life-long non smoker who has not used nicotine containing products.
- Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening.
- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, spirometry, vital signs, or ECGs, as deemed by the PI.
- Females must be of non-child bearing potential who must have undergone one of the following sterilization procedures at least 6 months prior to dosing in Part 1 or prior to the first dose in Part 2:
Key exclusion criteria (25 listed)
- Subject is mentally or legally incapacitated or has significant emotional problems at the time of screening visit or expected during the conduct of the study.
- History or presence of clinically significant medical condition(s) (including ongoing active infections) or psychiatric condition(s) or disease(s) in the opinion of the PI.
- History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- Abnormal spirometry test results, in the opinion of the PI.
- History of severe or unexplained adverse reactions during aerosol delivery of any 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: Granulocyte Macrophage-Colony Stimulating Factor (rhGM-CSF) | Drug | Molgramostim nebuliser solution, inhaled |
| PlaceboAlso: Nebuliser solution | Drug | Nebuliser solution, inhaled |
Primary outcome
Number and severity of treatment-emergent Adverse Events (AEs) following single and multiple inhaled doses of molgramostim
Time frame: 1-6 days
2 secondary outcomes
PK parameters: Area under the plasma concentration time curve (AUC), Peak Peak Plasma concentration - Cmax, Time to reach maximum observed serum concentration - tmax
Time frame: 1-6 days
PK parameters: Apparent terminal elimination rate constant - k(el) and Apparent terminal elimination rate constant - t(1/2)
Time frame: 1-6 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2017.
- Derived from this study: PubMed 40973220Trapnell BC, Carey BC, Robinson BR. Pharmacokinetics and pharmacodynamics of inhaled molgramostim in healthy people. BMJ Open Respir Res. 2025 Sep 18;12(1):e002832. doi: 10.1136/bmjresp-2024-002832.
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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.
Johnston Steward, MD principal investigator
Celerion
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Molgramostim in people with Pulmonary Alveolar Proteinosis and Bronchiectasis, run by Savara Inc. at 1 site in United Kingdom.
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 12 inclusion and 25 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: finished, as of the sponsor's last update on 23 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 and severity of treatment-emergent Adverse Events (AEs) following single and multiple inhaled doses of molgramostim (time frame: 1-6 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02468908, which also lists 1 linked publication.
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 23 Feb 2017.