Cystic FibrosisPhase 1/2NCT03748199
Clinical Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of POL6014 in Patients With CF
A Phase 1/2 study testing POL6014 in people with Cystic Fibrosis, run by Santhera Pharmaceuticals at 4 sites in Germany.
Trial summary
"This is a randomised, double-blind, placebo-controlled multi-centre study to investigate safety and tolerability and to provide pharmacokinetic and pharmacodynamics information of orally inhaled multiple doses (80 mg, 160 mg or 320 mg) of the nebulised neutrophil elastase inhibitor POL6014 in patients with Cystic… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- POL6014
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 4 sitesGermany
- Study dates
- 8 Nov 2018to 30 Dec 2020
- Phase
- Phase 1/2
- 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
- No healthy volunteers
- Adult
Who may be able to join
- Patient has given written informed consent to participation in the trial prior to their enrolment and any trial-related procedure.
- Male patients or female patients of non-childbearing potential, aged 18 to 55 years, inclusive. Women of non-childbearing potential are defined as those who have no uterus, or ligation of the fallopian tubes, or permanent cessation of ovarian function due to ovarian failure or surgical removal of the ovaries. Documentation of surgical procedure is required for patients who have had a hysterectomy or tubal ligation.
- Men must agree to practice contraception from start of study medication up to 90 days after the last dose of the study medication.
- Patient with a diagnosis of CF documented by a compatible clinical or radiographic presentation and laboratory criteria, more specifically, sweat or genetic testing (i.e., presence of the most common genetic defect ΔF 508 or any other mutation that can produce CF).
- Patient should confirm to produce frequently spontaneous sputum with a frequency of over 3 expectorates per day. Patient should be capable of producing a spontaneous sputum sample at screening (within a time range of approx. 3h during the screening visit).
- Except for CF and CF-related diseases, no other significant disease as assessed by a screening examination including medical history, physical examination, vital signs, ECG assessment, pulmonary function testing (PFT), and clinical laboratory results. Deviations of clinical laboratory results can be accepted if they are in accordance with the diagnosis of CF and CF-related diseases, supposed they do not indicate a clinical state that is expected to constitute a significant additional risk.
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- Patient must have an FEV1 ≥ 40% of predicted value at screening.
- Body mass index (BMI) between 16.5 and 30 (both inclusive).
- Non-smoker or ex-smoker who has stopped smoking for at least one (1) year prior to the Screening Visit.
- Patient should be willing to refrain from caffeine- or theophylline-containing products within 24 h prior to a clinic visit for a full PK profile.
- Ability to inhale in an appropriate manner (Patients will be trained to inhale from the eFlow® nebuliser device with a commercially available saline solution at the Screening Visit once informed consent has been obtained).
- For patients with routine courses of inhaled antibiotics, patients should agree to start routine course of inhaled antibiotic cycle on the same day or not earlier than 3 days before IMP administration.
Who cannot join
- Patient with unstable lung disease, as defined by a change in treatment regimen during the preceding two (2) weeks, or a significant new finding on chest radiography (such as, but not limited to, pneumothorax, lobar/segmental collapse or consolidation), or in the opinion of the investigator, patient with a decline in pulmonary status within the last 12 months not considered a part of the usual, chronic progression of CF lung disease. Routine cyclic antibiotic treatment regimens including "off/on" cycles are not considered to be changes to treatment regimens.
- Patient has had an exacerbation of respiratory symptoms within the past four (4) weeks before screening/randomization that required initiation of a new or altered respiratory therapy, and, in the opinion of the investigator, the patient has not returned to a stable level of health
- Patient with a history of lung transplantation.
- Patient with a history of clinically significant renal, hepatic, gastrointestinal,cardiovascular and particularly respiratory disease (excluding CF and CF-related disease).
- Patient with active gastrointestinal ulcer, history of intracranial bleedings, injuries and other bleedings.
- Patient, as per assessment of the investigator, with severe hepatic impairment (e.g. laboratory values (ALT, AST > 3 x ULN and total bilirubin > 1.5 x ULN) or Child-Pugh-Class C could be indicative of such condition).
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- ECG abnormalities of clinical relevance (e.g., QTc according to Bazett's formula ≥440 ms, PR >200 ms, or QRS ≥120 ms).
- Patient with a resting heart rate in supine position <50 bpm, systolic blood pressure <100 mmHg or >140 mmHg, diastolic blood pressure <60 mmHg or >90 mmHg.
- Proneness to orthostatic dysregulation, fainting, or blackouts.
- Diagnosis of a tricuspid insufficiency in combination with a mean pulmonary arterial pressure (mPAP) > 25 mmHg, measured by Doppler echography, or, if no tricuspid insufficiency is detectable, any echocardiographic or clinical signs of severe pulmonary heart disease (cor pulmonale) or depending congestive heart failure.
- History or presence of any malignancy.
- Positive results in any of the following virology tests: human immunodeficiency virus (HIV) antibodies and antigen, Anti-hepatitis B-core antibody, hepatitis B surface antigen (HbsAg) and anti-hepatitis C virus antibody.
- Known local or systemic hypersensitivity to any aerosol, medication or food that led to admission to an emergency room.
- Participation in another clinical study with any investigational medicinal product (IMP) or device, before randomisation, within an interval of 5 half-lives (minimum 4 weeks) from the last use of that investigational drug.
- Blood or plasma donation of more than 500 mL during the previous month before randomisation, as declared by the patient.
- Mental condition rendering the patient incapable to understand the nature, scope, and possible consequences of the study.
- Not willing to comply with all clinical study procedures.
Trial locations and contacts
4 sites in 1 country.
Germany4 sites
Charité - Uniklinik Berlin, Klinik für Pädiatrie,Pneumologie, Immunologie, Erwachsenene-Mucoviszidose
Berlin, 13353
Ruhrlandklinik Westdeutsches Lungenzentrum
Essen, 45239
IKF Pneumologie GmbH & Co. KG, Institut für klinische Forschung Pneumologie
Frankfurt, 60596
Inamed GmbH, clinical unit
Gauting, 82131
About this study
Official title: Phase-Ib/IIa Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Inhaled Multiple Doses of POL6014 in Patients With Cystic Fibrosis
"This is a randomised, double-blind, placebo-controlled multi-centre study to investigate safety and tolerability and to provide pharmacokinetic and pharmacodynamics information of orally inhaled multiple doses (80 mg, 160 mg or 320 mg) of the nebulised neutrophil elastase inhibitor POL6014 in patients with Cystic Fibrosis. The controlled inhalation will occur via the eFlow® nebuliser system (manufacturer: PARI Pharma GmbH, Germany)".
- Conditions
- Cystic Fibrosis
- Being tested
- POL6014, Placebo
- Keywords
- CF, cystic fibrosis, POL6014, neutrophil elastase inhibitor, anti-inflammatory
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
POL6014Drug
DL1 80 mg cohorts 1A and 1B (80 mg QD and 40 mg BID) DL2 160 mg cohorts 2A and 2B (160 mg QD and 80 mg BID) DL3 40 mg QD cohort C
DL = dose Level QD= quaque die (once daily) BID= bis in die (twice daily)
PlaceboDrug
Placebo will be administered orally at a dose and frequency matched to POL6014
| Study group | Role | What they receive |
|---|---|---|
| POL6014 | Experimental | multiple ascending doses: 80, 160 and 40 mg once or twice daily Receives: Drug: POL6014 |
| Placebo | Placebo comparator | Placebo will be administered orally at a dose and frequency matched to POL6014 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety measured by proportion of patients who experience potential clinically significant changes in physical examinations
Measured: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by number of patients with changes in laboratory assessments (clinical chemistry, haematology, urinanalysis)
Measured: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by number of patients with changes in vital signs (blood pressure, pulse, respiratory rate and body temperature)
Measured: Baseline and pre-dose through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by number of patients with changes in ECG parameters (heart rythm, ventricular rate, PR interval, QRS duration, Qt and QTc)
Measured: Baseline and pre-dose through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by occurrence and severity of adverse events
Measured: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by proportion of subjects who experience local irritation of the nose or pharynx by visual inspection
Measured: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by proportion of patients who experience bronchospasm
Measured: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by changes in lung function parameters (FEV1, FVC)
Measured: Baseline and pre-dose through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by changes in oxygen saturation in peripheral blood as measured by pulse oximetry
Measured: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Tolerability assessed by the number of patients who discontinue the study treatment prematurely due to Adverse Events
Measured: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Secondary outcomes (1)
Pharmacokinetics (PK) for POL6014 and metabolites in plasma, sputum and urine
Concentration of POL6014 and relevant metabolites measured in plasma, sputum and urine
Measured: At defined timepoints (Day1, Day 2, Day 8, Day 14, Day 15, Day 16)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2018
- Study start8 Nov 2018
- Primary completion30 Dec 2020
- Study completion30 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Santhera Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03748199
- Sponsor's protocol ID
- SNT-I-018
- Status last verified
- Mar 2021
- First submitted
- 5 Nov 2018
- Last updated
- 28 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase-Ib/IIa Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Inhaled Multiple Doses of POL6014 in Patients With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT03748199
- Acronym / sponsor ID
- SNT-I-018
- Conditions
- Cystic Fibrosis
- Keywords
- CF, cystic fibrosis, POL6014, neutrophil elastase inhibitor, anti-inflammatory
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Santhera PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 Nov 2018 (actual)
- Primary completion
- 30 Dec 2020 (actual)
- Study completion
- 30 Dec 2020 (actual)
- First posted
- 20 Nov 2018 (actual)
- 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 randomised, double-blind, placebo-controlled multi-centre study to investigate safety and tolerability and to provide pharmacokinetic and pharmacodynamics information of orally inhaled multiple doses (80 mg, 160 mg or 320 mg) of the nebulised neutrophil elastase inhibitor POL6014 in patients with Cystic Fibrosis. The controlled inhalation will occur via the eFlow® nebuliser system (manufacturer: PARI Pharma GmbH, Germany)".
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| POL6014 | Experimental | Drug: POL6014multiple ascending doses: 80, 160 and 40 mg once or twice daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo will be administered orally at a dose and frequency matched to POL6014 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Patient has given written informed consent to participation in the trial prior to their enrolment and any trial-related procedure.
- Male patients or female patients of non-childbearing potential, aged 18 to 55 years, inclusive. Women of non-childbearing potential are defined as those who have no uterus, or ligation of the fallopian tubes, or permanent cessation of ovarian function due to ovarian failure or surgical removal of the ovaries. Documentation of surgical procedure is required for patients who have had a hysterectomy or tubal ligation.
- Men must agree to practice contraception from start of study medication up to 90 days after the last dose of the study medication.
- Patient with a diagnosis of CF documented by a compatible clinical or radiographic presentation and laboratory criteria, more specifically, sweat or genetic testing (i.e., presence of the most common genetic defect ΔF 508 or any other mutation that can produce CF).
- Patient should confirm to produce frequently spontaneous sputum with a frequency of over 3 expectorates per day. Patient should be capable of producing a spontaneous sputum sample at screening (within a time range of approx. 3h during the screening visit).
Key exclusion criteria (17 listed)
- Patient with unstable lung disease, as defined by a change in treatment regimen during the preceding two (2) weeks, or a significant new finding on chest radiography (such as, but not limited to, pneumothorax, lobar/segmental collapse or consolidation), or in the opinion of the investigator, patient with a decline in pulmonary status within the last 12 months not considered a part of the usual, chronic progression of CF lung disease. Routine cyclic antibiotic treatment regimens including "off/on" cycles are not considered to be changes to treatment regimens.
- Patient has had an exacerbation of respiratory symptoms within the past four (4) weeks before screening/randomization that required initiation of a new or altered respiratory therapy, and, in the opinion of the investigator, the patient has not returned to a stable level of health
- Patient with a history of lung transplantation.
- Patient with a history of clinically significant renal, hepatic, gastrointestinal,cardiovascular and particularly respiratory disease (excluding CF and CF-related disease).
- Patient with active gastrointestinal ulcer, history of intracranial bleedings, injuries and other bleedings.
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 |
|---|---|---|
| POL6014DL1 80 mg cohorts 1A and 1B (80 mg QD and 40 mg BID) DL2 160 mg cohorts 2A and 2B (160 mg QD and 80 mg BID) DL3 40 mg QD cohort C DL = dose Level QD= quaque die (once daily) BID= bis in die (twice daily) | Drug | POL6014 |
| PlaceboPlacebo will be administered orally at a dose and frequency matched to POL6014 | Drug | Placebo |
Primary outcome
Safety measured by proportion of patients who experience potential clinically significant changes in physical examinations
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by number of patients with changes in laboratory assessments (clinical chemistry, haematology, urinanalysis)
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by number of patients with changes in vital signs (blood pressure, pulse, respiratory rate and body temperature)
Time frame: Baseline and pre-dose through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by number of patients with changes in ECG parameters (heart rythm, ventricular rate, PR interval, QRS duration, Qt and QTc)
Time frame: Baseline and pre-dose through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by occurrence and severity of adverse events
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by proportion of subjects who experience local irritation of the nose or pharynx by visual inspection
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by proportion of patients who experience bronchospasm
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by changes in lung function parameters (FEV1, FVC)
Time frame: Baseline and pre-dose through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by changes in oxygen saturation in peripheral blood as measured by pulse oximetry
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Tolerability assessed by the number of patients who discontinue the study treatment prematurely due to Adverse Events
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
1 secondary outcome
Pharmacokinetics (PK) for POL6014 and metabolites in plasma, sputum and urine
Time frame: At defined timepoints (Day1, Day 2, Day 8, Day 14, Day 15, Day 16)
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 28 Sep 2021.
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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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing POL6014 in people with Cystic Fibrosis, run by Santhera Pharmaceuticals at 4 sites in Germany.
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 17 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 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Safety measured by proportion of patients who experience potential clinically significant changes in physical examinations (time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)). The study lists 10 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 28 Sep 2021.