A Study of RPL554 in Patients With Cystic Fibrosis

NCT02919995 | Completed Phase 2 Results

• 2 other identifiers: RPL554-010-20152015-004263-36
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (4)

• AUC by Dose

  Area under the curve (AUC)

  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

  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

  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

  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

  Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose after treatment

• AUC FEV1(0-4h)

  Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose

• AUC FEV1(0-6h)

  Pre dose and 15 and 30 minutes and 1, 2, 4 and 6 hours post dose

• AUC FEV1(0-8h)

  pre dose and 15 and 30 minutes and 1, 2, 4, 6 and 8 hours post dose

• FVC

  Over 24 hours after treatment

Other Outcomes (2)

• Sputum Rheology

  8 and 12 hours after treatment

• Sputum Measurements

  8 and 12 hours after treatment

Study Arms (3)

Higher Dose RPL554

EXPERIMENTAL

Single dose of inhaled 6 mg RPL554

Drug: RPL554

Lower dose RPL554

EXPERIMENTAL

Single dose of inhaled 1.5 mg RPL554

Drug: RPL554

Placebo

PLACEBO COMPARATOR

Inhaled placebo dose

Drug: Placebo

Interventions

RPL554 DRUG

RPL554 suspension administered using a nebuliser

Higher Dose RPL554; Lower dose RPL554

Placebo DRUG

Placebo solution administered using a nebuliser

Placebo

Eligibility Criteria

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

You may qualify if:

• \. 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.
• \. 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.
• \. 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
• 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.
• \. Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) with a minimum weight of 40 kg.
• \. Patients with a genetic diagnosis of CF. 7. Spirometry at screening demonstrating an FEV1 ≥40% and ≤80% of predicted normal.
• \. 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.
• \. Clinically stable CF in the 2 weeks prior to randomisation (Visit 2).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Verona Pharma plc: lead
• Cystic Fibrosis Trust: collaborator

Study Sites (1)

Papworth Hospital

Cambridge, CB23 3RE, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ensifentrine

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Brian Maurer
• Organization: Verona Pharma plc

brian.maurer@veronapharma.com

+19147675037

Study Officials

• Andres Floto

  Cambridge Centre for Medical Research, Papworth Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2016
• First Posted: September 30, 2016
• Study Start: February 8, 2017
• Primary Completion: November 3, 2017
• Study Completion: November 3, 2017
• Last Updated: May 21, 2024
• Results First Posted: March 20, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)