Clinical trial NCT04441788: A Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Participants With Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) With Chronic Bronchitis (CB)
Official title: A Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate COPD With Chronic Bronchitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Bronchitis
Chronic Obstructive Pulmonary Disease
Keywords: Chronic Bronchitis
IONIS-ENaCRx
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-22
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the effect of ION-827359 on forced expiratory volume in 1 second (FEV1) in participants with mild to moderate COPD with CB.

Detailed description: This was a multi-center, double-blind, placebo-controlled, randomized, Phase 2a study of ION-827359 in up to 180 participants. The participants were randomized to receive oral inhalation of either ION-827359 or placebo for up to 13 weeks. At the end of 13 weeks, participants entered a 10-week post-treatment evaluation period.

Eligibility criteria: Inclusion Criteria

1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements
2. Males or females. Aged 40-70 inclusive at the time of informed consent
3. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or postmenopausal
4. BMI \< 35.0 kg/m\^2
5. Participants with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)

   1. Ability to perform acceptable and reproducible spirometry
   2. Post-bronchodilator (4 puffs of albuterol) spirometry at Screening demonstrating the following:

   i. FEV1/ forced vital capacity (FVC) ratio of \< 0.70 ii. FEV1 ≥ 50% and ≤ 90% of predicted normal
6. Clinically stable COPD in the 4 weeks prior to Screening (Visit 1)
7. Current and former smokers with smoking history of ≥ 20 pack years
8. Meet SGRQ definition of CB
9. CAT score ≥ 10

Exclusion Criteria

1. Clinically significant abnormalities in medical history (e.g., previous acute coronary syndrome within 6 months of screening, congestive heart failure, major surgery within 3 months of Screening) or physical examination
2. Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a subject unsuitable for inclusion

   1. Urine protein/creatinine (P/C) ratio ≥ 0.3 mg/mg. In the event of P/C ratio above this threshold eligibility may be confirmed by a quantitative total urine protein measurement of \< 300 mg/24 hr
   2. Positive test (including trace) for blood on urinalysis. In the event of a positive test eligibility may be confirmed with urine microscopy showing ≤ 5 red blood cells per high power field
   3. alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN) \> 1.5 × upper limit of normal (ULN)
   4. Platelet count \< LLN
   5. Serum potassium \> 5.2 mmol/L
   6. Estimated GFR \< 60 mL/min (as determined by the Cockcroft-Gault Equation for creatinine clearance)
   7. A positive PCR test for SARS-CoV-2 at any time prior to randomization
3. Any active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to first day Study Drug product is administered to the participant (Study Day 1)
4. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
5. Clinically important pulmonary disease other than COPD
6. Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines (GINA 2011) or other accepted guidelines. Participants with a past medical history of asthma (e.g. childhood or adolescence) may be included
7. Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 4 weeks prior to enrolment (Visit 1)
8. Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 4 weeks prior to enrolment (Visit 1)
9. Long term oxygen therapy (LTOT)
10. Participants participating in, or scheduled for, an intensive (active) COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible to take part)
11. Concomitant medication restrictions: Oral anticoagulants, oral steroids (e.g. prednisone or Medrol), theophylline, chronic azithromycin, or roflumilast
12. Have any other conditions, which, in the opinion of the Investigator would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

Primary outcomes:
measure: Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo
timeFrame: From Baseline up to average of Weeks 13 and 14
Secondary outcomes:
measure: Change From Baseline in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Respiratory Symptoms (E-RS) Daily Symptom Diary Total Score to the Primary Time Point
timeFrame: From Baseline up to average of weeks 13 and 14
measure: Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point
timeFrame: From Baseline to Week 14
measure: Change From Baseline in St. George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score to the Week 14 Time Point
timeFrame: From Baseline to Week 14
measure: Change From Baseline in Post-Bronchodilator FEV1
timeFrame: From Baseline to end of treatment (EOT) [Up to Week 14]
measure: Cmax: Maximum Observed Plasma Concentration for ION-827359
timeFrame: Days 1 and 85
measure: Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359
timeFrame: Days 1 and 85
measure: AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359
timeFrame: Days 1 and 85
measure: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity
timeFrame: Up to Week 24
measure: Percentage of Participants With Clinically Significant Change in Laboratory Values
timeFrame: Up to Week 24
measure: Percentage of Participants With Clinically Significant Change in Vital Sign Parameters
timeFrame: Up to Week 24
measure: Percentage of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Jindrichuv Hradec
country: Czechia
facility: MediTrial s.r.o.
city: Kralupy Nad Vltavou
country: Czechia
facility: Plicni ambulance Kralupy
city: Lovosice
country: Czechia
facility: CEFISPIRO s.r.o.
city: Rokycany
country: Czechia
facility: Plicni Ambulance Rokycany, s.r.o.
city: Varnsdorf
country: Czechia
facility: PNEUMOLOGIE VARNSDORF s.r.o.
city: Berlin
country: Germany
facility: Pneumologisches Studienzentrum Markgrafenstrasse
city: Berlin
country: Germany
facility: MECS Research GmbH
city: Grosshansdorf
country: Germany
facility: Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
city: Hamburg
country: Germany
facility: Hamburger Institut far Therapieforschung GmbH
city: Lübeck
country: Germany
facility: KLB Gesundheitsforschung Lubeck GmbH
city: Mainz
country: Germany
facility: IKF Pneumologie Mainz Helix Medical Excellence Center Mainz
city: Warendorf
country: Germany
facility: ZMS-Zentrum fur medizinische Studien GmbH
city: Deszk
country: Hungary
facility: Csongrad Megyei Mellkasi Betegsegek Szakkorhaza
city: Komarom
country: Hungary
facility: Selye Janos Korhaz, Rendelointezet
city: London
country: United Kingdom
facility: Queen Anne Street Medical Centre, Heart Lung Center
Study officials:
References: