Cystic FibrosisPhase 2NCT02919995
A Study of RPL554 in Patients With Cystic Fibrosis
A Phase 2 study testing RPL554 in people with Cystic Fibrosis, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 1 site in United Kingdom.
Trial summary
This study evaluates two doses of RPL554 and placebo in adult patients with cystic fibrosis. All patients receive all three treatments in a randomised sequence. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- RPL554
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Feb 2017to 3 Nov 2017
- Phase
- Phase 2
- 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
- 1. Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
- 2. Male or female aged ≥18 years at the time of informed consent. Females of childbearing potential must have been using a consistent and reliable form of contraception (see Appendix 1) from the last menses before the first study treatment administration, and must commit to continue to do so during the study and for 3 months after the last dose of study treatment.
- 3. Have a 12-lead ECG recording at screening (Visit 1) and Visit 2 pre-dose showing the following:
- Heart rate between 45 and 90 beats per minute
- QT interval corrected for heart rate using Fridericia's formula (QTcF) interval ≤450 msec
- QRS interval ≤120 msec
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- PR interval ≤220 msec
- No clinically significant abnormality including morphology (e.g. left bundle branch block, atrioventricular nodal dysfunction, ST segment abnormalities) 4. Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.
- 5. Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) with a minimum weight of 40 kg.
- 6. Patients with a genetic diagnosis of CF. 7. Spirometry at screening demonstrating an FEV1 ≥40% and ≤80% of predicted normal.
- 8. Capable of withdrawing from long acting bronchodilators1 until the end of the treatment period, and short acting bronchodilators for 8 hours prior to administration of study treatment.
- 9. Clinically stable CF in the 2 weeks prior to randomisation (Visit 2).
Who cannot join
- History of cirrhotic liver disease or portal hypertension.
- CF exacerbation requiring hospitalisation in the month prior to screening (Visit 1) or prior to randomisation (Visit 2).
- Use of oral or intravenous antibiotics (in additional to usual maintenance therapy) in the 2 weeks prior to screening (Visit 1) or randomisation (Visit 2).
- Other non-CF related respiratory disorders: Patients with a current diagnosis of active tuberculosis, lung cancer, sarcoidosis, sleep apnoea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
- Previous lung resection or lung transplant.
- History of, or reason to believe a patient has, drug or alcohol abuse within the past 3 years.
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- Received an experimental drug within 3 months or five half-lives, whichever is longer.
- Patients with a history of chronic uncontrolled disease including, but not limited to, cardiovascular (including arrhythmias), endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, haematological, urological, immunological or ophthalmic diseases that the Investigator believes are clinically significant.
- Documented cardiovascular disease: angina, recent or suspected myocardial infarction, congestive heart failure, a history of unstable, or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months.
- Has had major surgery, (requiring general anaesthesia) in the 6 weeks prior to screening (Visit 1) or will not have fully recovered from surgery, or planned surgery through the end of the study.
- Infection with nontuberculous mycobacteria, methicillin-resistant Staphylococcus aureus (MRSA), or Burkholderia species.
- Use of immune-suppression; long term use of prednisolone ≥10 mg/day.
- History of malignancy of any organ system within 5 years with the exception of localised skin cancers (basal or squamous cell).
- Clinically significant abnormal values for safety laboratory tests (haematology, biochemistry or urinalysis) at screening (Visit 1), as determined by the Investigator.
- A disclosed history or one known to the Investigator, of significant non-compliance in previous investigational studies or with prescribed medications.
- Requires oxygen therapy, even on an occasional basis.
- Pregnancy or lactation (female subjects only).
- Any other reason that the Investigator considers makes the patient unsuitable to participate. -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IIa, Randomised, Double Blind, Placebo Controlled, Three Way Crossover Study to Assess the Pharmacokinetics of RPL554 Administered to Adult Patients With Cystic Fibrosis.
This study evaluates two doses of RPL554 and placebo in adult patients with cystic fibrosis. All patients receive all three treatments in a randomised sequence.
- Conditions
- Cystic Fibrosis
- Being tested
- RPL554, Placebo
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RPL554Drug
RPL554 suspension administered using a nebuliser
PlaceboDrug
Placebo solution administered using a nebuliser
| Study group | Role | What they receive |
|---|---|---|
| Higher Dose RPL554 | Experimental | Single dose of inhaled 6 mg RPL554 Receives: Drug: RPL554 |
| Lower dose RPL554 | Experimental | Single dose of inhaled 1.5 mg RPL554 Receives: Drug: RPL554 |
| Placebo | Placebo comparator | Inhaled placebo dose Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC by Dose
Area under the curve (AUC)
Measured: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose after each treatment
Maximum Plasma Concentration After Each Dose
Maximum plasma concentration (Cmax) after a single dose of RPL554
Measured: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose
Time to Maximum Plasma Concentration After Each Dose
Time to maximum concentration (Tmax) after a single dose of RPL554
Measured: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose
Half Life for Each Dose
Half life (t1/2) of RPL554
Measured: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose
Secondary outcomes (13)
Peak FEV1 for Each Treatment
Maximum Forced expired volume in one second (FEV1) measured using spirometry
Measured: Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose after treatment
AUC FEV1(0-4h)
Area under the curve for FEV1 over 4 hours measured using spirometry
Measured: Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose
AUC FEV1(0-6h)
Area under the curve FEV1 over 6 hours measured using spirometry
Measured: Pre dose and 15 and 30 minutes and 1, 2, 4 and 6 hours post dose
AUC FEV1(0-8h)
Area under the curve for FEV1 over 8 hours measured using spirometry
Measured: pre dose and 15 and 30 minutes and 1, 2, 4, 6 and 8 hours post dose
FVC
Forced vital capacity (FVC) measured using spirometry
Measured: Over 24 hours after treatment
Breath Samples
Exhaled breath pH
Measured: 8 and 24 hours after treatment
Laboratory Safety Tests 1
Biochemistry panel parameters
Measured: Screening and end of study
Laboratory Safety Tests 2
Haematology panel parameters
Measured: Screening and end of study
Laboratory Safety Tests 3
Urinalysis measured by urine dipstick
Measured: Screening and end of study
Vital Signs 1
Pulse rate after 5 minutes supine
Measured: Over 8 hours after treatment
Vital Signs 2
Blood pressure after 5 minutes supine
Measured: Over 8 hours after treatment
ECG 1
Heart rate
Measured: Over 8 hours after treatment
ECG 2
QT interval
Measured: Over 8 hours after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2016 (estimated)
- Study start8 Feb 2017
- Primary completion3 Nov 2017
- Study completion3 Nov 2017
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 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cystic Fibrosis Trust
- Responsible party
- Sponsor
- Investigators
- Andres Floto, Principal investigator, Cambridge Centre for Medical Research, Papworth Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02919995
- Sponsor's protocol ID
- RPL554-010-2015
- Other IDs
- 2015-004263-36, 2015
- Status last verified
- May 2019
- First submitted
- 21 Sep 2016
- Last updated
- 21 May 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 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa, Randomised, Double Blind, Placebo Controlled, Three Way Crossover Study to Assess the Pharmacokinetics of RPL554 Administered to Adult Patients With Cystic Fibrosis.
- ClinicalTrials.gov ID
- NCT02919995
- Acronym / sponsor ID
- RPL554-010-2015
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USAIndustry (pharma, biotech, devices)
- Collaborators
- Cystic Fibrosis Trust
- Study start
- 8 Feb 2017 (actual)
- Primary completion
- 3 Nov 2017 (actual)
- Study completion
- 3 Nov 2017 (actual)
- First posted
- 30 Sep 2016 (estimated)
- Results
- Posted 20 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates two doses of RPL554 and placebo in adult patients with cystic fibrosis. All patients receive all three treatments in a randomised sequence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Higher Dose RPL554 | Experimental | Drug: RPL554Single dose of inhaled 6 mg RPL554 |
| Lower dose RPL554 | Experimental | Drug: RPL554Single dose of inhaled 1.5 mg RPL554 |
| Placebo | Placebo comparator | Drug: PlaceboInhaled placebo dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 1. Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
- 2. Male or female aged ≥18 years at the time of informed consent. Females of childbearing potential must have been using a consistent and reliable form of contraception (see Appendix 1) from the last menses before the first study treatment administration, and must commit to continue to do so during the study and for 3 months after the last dose of study treatment.
- 3. Have a 12-lead ECG recording at screening (Visit 1) and Visit 2 pre-dose showing the following:
- 5. Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) with a minimum weight of 40 kg.
- 6. Patients with a genetic diagnosis of CF. 7. Spirometry at screening demonstrating an FEV1 ≥40% and ≤80% of predicted normal.
Key exclusion criteria (18 listed)
- History of cirrhotic liver disease or portal hypertension.
- CF exacerbation requiring hospitalisation in the month prior to screening (Visit 1) or prior to randomisation (Visit 2).
- Use of oral or intravenous antibiotics (in additional to usual maintenance therapy) in the 2 weeks prior to screening (Visit 1) or randomisation (Visit 2).
- Other non-CF related respiratory disorders: Patients with a current diagnosis of active tuberculosis, lung cancer, sarcoidosis, sleep apnoea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
- Previous lung resection or lung transplant.
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 |
|---|---|---|
| RPL554RPL554 suspension administered using a nebuliser | Drug | Higher Dose RPL554, Lower dose RPL554 |
| PlaceboPlacebo solution administered using a nebuliser | Drug | Placebo |
Primary outcome
AUC by Dose
Time frame: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose after each treatment
Area under the curve (AUC)
Maximum Plasma Concentration After Each Dose
Time frame: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose
Maximum plasma concentration (Cmax) after a single dose of RPL554
Time to Maximum Plasma Concentration After Each Dose
Time frame: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose
Time to maximum concentration (Tmax) after a single dose of RPL554
Half Life for Each Dose
Time frame: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose
Half life (t1/2) of RPL554
13 secondary outcomes
Peak FEV1 for Each Treatment
Time frame: Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose after treatment
AUC FEV1(0-4h)
Time frame: Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose
AUC FEV1(0-6h)
Time frame: Pre dose and 15 and 30 minutes and 1, 2, 4 and 6 hours post dose
AUC FEV1(0-8h)
Time frame: pre dose and 15 and 30 minutes and 1, 2, 4, 6 and 8 hours post dose
FVC
Time frame: Over 24 hours after treatment
Breath Samples
Time frame: 8 and 24 hours after treatment
Laboratory Safety Tests 1
Time frame: Screening and end of study
Laboratory Safety Tests 2
Time frame: Screening and end of study
Laboratory Safety Tests 3
Time frame: Screening and end of study
Vital Signs 1
Time frame: Over 8 hours after treatment
Vital Signs 2
Time frame: Over 8 hours after treatment
ECG 1
Time frame: Over 8 hours after treatment
ECG 2
Time frame: Over 8 hours after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 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.
Andres Floto principal investigator
Cambridge Centre for Medical Research, Papworth Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RPL554 in people with Cystic Fibrosis, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA 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 18 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 21 May 2024. 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 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?
Yes. Results are posted in the registry (first posted 20 Mar 2019). 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?
AUC by Dose (time frame: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose after each treatment). 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 21 May 2024.