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)

NCT ID: NCT04441788

Last Updated: 2022-12-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-22
• Study Completion Date: 2021-08-09

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.

Conditions

Chronic Bronchitis; Chronic Obstructive Pulmonary Disease

Keywords

Chronic Bronchitis; IONIS-ENaCRx

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Single-dose of placebo was administered by oral inhalation via nebulizer, once every week for up to 13 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo administered by oral inhalation

ION-827359 37.5 milligrams (mg)

Single-dose of ION-827359 37.5 mg was administered by oral inhalation via nebulizer, once every week for up to 13 weeks.

Group Type: EXPERIMENTAL

ION-827359

Intervention Type: DRUG

ION-827359 administered by oral inhalation

ION-827359 75 mg

Single-dose of ION-827359 75 mg was administered by oral inhalation via nebulizer, once every week for up to 13 weeks.

Group Type: EXPERIMENTAL

ION-827359

Intervention Type: DRUG

ION-827359 administered by oral inhalation

Interventions

ION-827359

ION-827359 administered by oral inhalation

Intervention Type: DRUG

Placebo

Placebo administered by oral inhalation

Intervention Type: DRUG

ION-827359

ION-827359 administered by oral inhalation

Intervention Type: DRUG

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Plicni ambulance Kralupy

Kralupy nad Vltavou, , Czechia

CEFISPIRO s.r.o.

Lovosice, , Czechia

Plicni Ambulance Rokycany, s.r.o.

Rokycany, , Czechia

PNEUMOLOGIE VARNSDORF s.r.o.

Varnsdorf, , Czechia

MediTrial s.r.o.

Jindřichův Hradec, , Czechia

Pneumologisches Studienzentrum Markgrafenstrasse

Berlin, , Germany

MECS Research GmbH

Berlin, , Germany

Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH

Großhansdorf, , Germany

Hamburger Institut far Therapieforschung GmbH

Hamburg, , Germany

KLB Gesundheitsforschung Lubeck GmbH

Lübeck, , Germany

IKF Pneumologie Mainz Helix Medical Excellence Center Mainz

Mainz, , Germany

ZMS-Zentrum fur medizinische Studien GmbH

Warendorf, , Germany

Csongrad Megyei Mellkasi Betegsegek Szakkorhaza

Deszk, , Hungary

Selye Janos Korhaz, Rendelointezet

Komárom, , Hungary

Queen Anne Street Medical Centre, Heart Lung Center

London, , United Kingdom

Countries

Czechia; Germany; Hungary; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2020-000210-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ION-827359-CS2

Identifier Type: -

Identifier Source: org_study_id