Dose Ranging Study of RPL554 in Chronic Obstructive Pulmonary Disease (COPD) Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03443414
• Date of registration: 07/02/2018
• Prospective Registration: No
• Primary sponsor: Verona Pharma plc
• Public title: Dose Ranging Study of RPL554 in Chronic Obstructive Pulmonary Disease (COPD) Patients
• Scientific title: Phase IIb, Randomized, Double Blind, Placebo Controlled, Dose Ranging Study to Assess the Effect of RPL554 in Patients With Moderate to Severe COPD.
• Date of first enrolment: June 1, 2017
• Target sample size: 405
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03443414
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Bulgaria, Czechia, Germany, Poland, Romania, United Kingdom

Contacts

• Name: Dr Singh
• Affiliation: Medicines Evaluation Unit (MEU)

Key inclusion & exclusion criteria

Inclusion Criteria:

- Provide informed consent

- Male or female aged 40 to 75 years

- Meeting specified contraception requirements

- 12-lead electrocardiogram with heart rate 50-90 beats per minute, QT interval
corrected using Fridericia's formula (QTcF) =450 msec (males) or =470 msec (females),
QRS interval =120 msec, PR interval =200 msec and no clinically significant
abnormalities

- Capable of complying with all study restrictions and procedures, including ability to
use the study nebulizer correctly.

- Body mass index (BMI) 18 to 35 kg/m2 and minimum weight 45 kg.

- COPD diagnosis with symptoms compatible with COPD for at least 1 year

- Clinically stable COPD in the previous 4 weeks

- Ability to perform acceptable and reproducible spirometry.

- Post-bronchodilator spirometry at screening must demonstrate FEV1/forced vital
capacity (FVC) ratio of =0.70 and FEV1 must be =40 % to =80% of predicted normal

- Chest X-ray (posterior-anterior) at screening, or chest X-ray, magnetic resonance
imaging (MRI) or computed tomography (CT) scan in the last 12 months, showing no
abnormalities which are both clinically significant and unrelated to COPD.

- Meet the concomitant medication restrictions and be expected to do so for the rest of
the study.

- Current and former smokers with a smoking history of =10 pack years.

- Capable of withdrawing long acting bronchodilators until the end of the treatment
period, and short acting bronchodilators for 8 hours prior to administration of study
medication.

Exclusion Criteria:

- A history of life-threatening COPD including Intensive Care Unit admission and
requiring intubation.

- COPD exacerbation requiring oral steroids in the previous 3 months

- A history of one or more hospitalizations for COPD in the previous 6 months

- Lower respiratory tract infection treated with antibiotics in the previous 3 months

- Evidence of cor pulmonale or clinically significant pulmonary hypertension.

- Patients with a current diagnosis of asthma, active tuberculosis, lung cancer,
bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea,
known alpha-1 antitrypsin deficiency or other active pulmonary diseases.

- Previous lung resection or lung reduction surgery.

- Oral therapies for COPD (e.g. oral steroids, theophylline, and roflumilast) in the
previous 3 months and throughout the study.

- Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to
Visit 1) and remains stable during the trial.

- A history of, or reason to believe a subject has, drug or alcohol abuse in the
previous 3 years.

- Received an experimental drug within 30 days or five half-lives of the first dose

- Prior exposure to RPL554.

- Women who are pregnant or breast-feeding.

- Patients with a history of current uncontrolled disease that the Investigator believes
are clinically significant.

- myocardial infarction in the previous 6 month; congestive heart failure, a history of
unstable or uncontrolled hypertension, or has been diagnosed with hypertension in last
3 months.

- Use of oral beta blockers.

- Major surgery (requiring general anesthesia) in the previous 6 weeks, lack of full
recovery from surgery at screening, or planned surgery through the end of the study.

- History of malignancy of any organ system within 5 years, with the exception of
localized skin cancers (basal or squamous cell).

- Clinically significant abnormal values for safety laboratory tests

- Significant non-compliance in previous investigational studies or with prescribed
medications.

- Requirement for oxygen therapy, even on an occasional basis.

- Known hypersensitivity to RPL554 or its excipients/components.

- Abnormal clinically significant 12 lead Holter findings,

- Any other reason that the Investigator considers makes the subject unsuitable to
participate.



Age minimum: 40 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

COPD

Intervention(s)

Drug: Placebo

Drug: RPL554 suspension

Primary Outcome(s)

Mean Change From Baseline in Peak FEV1 (Over 3 Hours) at Week 4 [Time Frame: Baseline (pre-dose, Visit 2) and Week 4 (Visit 6).]

Secondary Outcome(s)

Mean Change From Baseline FEV1 to Average FEV1 (Over 12 Hours) at Day 1 and Week 4 [Time Frame: Baseline (pre-dose, Visit 2), up to 12 hours post-dose at Visit 2 (Day 1) and Visit 6 (Week 4).]

Number of Patients With Treatment Emergent Adverse Events (TEAEs) [Time Frame: Up to end of study (approximately 6 weeks)]

Mean Change From Baseline in Breathlessness as Assessed Using the St George's Respiratory Questionnaire (SGRQ) at Week 4 [Time Frame: Baseline (pre-dose, Visit 2) and Week 4 (Visit 6).]

Mean Change From Baseline in COPD Symptoms Using the Exacerbations of Chronic Pulmonary Disease Tool Patient-Reported Outcome (EXACT-PRO) Scoring at Week 4 [Time Frame: Baseline (pre-dose, Visit 2) and Week 4 (Visit 6).]

Mean Change From Baseline FEV1 to Morning Trough FEV1 at Week 4 [Time Frame: Baseline (pre-dose, Visit 2) and Week 4 (Visit 6).]

Secondary ID(s)

RPL554-CO-203

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 04/06/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03443414