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)

NCT04441788 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ION-827359-CS22020-000210-15
• Study Type: interventional
• Target: 60
• Locations: 4 countries
• Sites: 15

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.

Conditions

Chronic Bronchitis; Chronic Obstructive Pulmonary Disease

Keywords

Chronic Bronchitis; IONIS-ENaCRx

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo

  FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Baseline was defined as the last non-missing measurement prior to the first study drug administration. The primary time point was defined as the average of weeks 13 and 14. FAS=Full analysis set.

  From Baseline up to average of Weeks 13 and 14

Secondary Outcomes (11)

• 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

  From Baseline up to average of weeks 13 and 14

• Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point

  From Baseline to Week 14

• Change From Baseline in St. George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score to the Week 14 Time Point

  From Baseline to Week 14

• Change From Baseline in Post-Bronchodilator FEV1

  From Baseline to end of treatment (EOT) [Up to Week 14]

• Cmax: Maximum Observed Plasma Concentration for ION-827359

  Days 1 and 85

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

ION-827359 37.5 milligrams (mg)

EXPERIMENTAL

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

Drug: ION-827359

ION-827359 75 mg

EXPERIMENTAL

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

Drug: ION-827359

Interventions

ION-827359 DRUG

ION-827359 administered by oral inhalation

ION-827359 37.5 milligrams (mg)

Placebo DRUG

Placebo administered by oral inhalation

Placebo

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Males or females. Aged 40-70 inclusive at the time of informed consent
• Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or postmenopausal
• BMI \< 35.0 kg/m\^2
• Participants with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)
• Ability to perform acceptable and reproducible spirometry
• 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
• Clinically stable COPD in the 4 weeks prior to Screening (Visit 1)
• Current and former smokers with smoking history of ≥ 20 pack years
• Meet SGRQ definition of CB
• CAT score ≥ 10

You may not qualify if:

• 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
• 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
• 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
• alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN) \> 1.5 × upper limit of normal (ULN)
• Platelet count \< LLN
• Serum potassium \> 5.2 mmol/L
• Estimated GFR \< 60 mL/min (as determined by the Cockcroft-Gault Equation for creatinine clearance)
• A positive PCR test for SARS-CoV-2 at any time prior to randomization
• 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)
• Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
• Clinically important pulmonary disease other than COPD
• 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
• Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 4 weeks prior to enrolment (Visit 1)
• Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 4 weeks prior to enrolment (Visit 1)
• Long term oxygen therapy (LTOT)

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (15)

MediTrial s.r.o.

Jindřichův Hradec, 37701, Czechia

Location

Plicni ambulance Kralupy

Kralupy nad Vltavou, 27801, Czechia

Location

CEFISPIRO s.r.o.

Lovosice, 410 02, Czechia

Location

Plicni Ambulance Rokycany, s.r.o.

Rokycany, 33701, Czechia

Location

PNEUMOLOGIE VARNSDORF s.r.o.

Varnsdorf, 40747, Czechia

Location

Pneumologisches Studienzentrum Markgrafenstrasse

Berlin, 10969, Germany

Location

MECS Research GmbH

Berlin, 12203, Germany

Location

Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927, Germany

Location

Hamburger Institut far Therapieforschung GmbH

Hamburg, 20354, Germany

Location

KLB Gesundheitsforschung Lubeck GmbH

Lübeck, 23552, Germany

Location

IKF Pneumologie Mainz Helix Medical Excellence Center Mainz

Mainz, 55128, Germany

Location

ZMS-Zentrum fur medizinische Studien GmbH

Warendorf, 48231, Germany

Location

Csongrad Megyei Mellkasi Betegsegek Szakkorhaza

Deszk, 6772, Hungary

Location

Selye Janos Korhaz, Rendelointezet

Komárom, 2900, Hungary

Location

Queen Anne Street Medical Centre, Heart Lung Center

London, Nw1 8HU, United Kingdom

Location

MeSH Terms

Conditions

Bronchitis, Chronic; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was terminated based on the toxicology findings from a 9-month study and participants who had not completed the treatment period were instructed to terminate dosing and return for an end of study visit, followed by the 10-week follow-up period.

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc
• Organization: Ionis Pharmaceuticals, Inc

patients@ionisph.com

800-679-4747

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 22, 2020
• Study Start: December 22, 2020
• Primary Completion: April 27, 2021
• Study Completion: August 9, 2021
• Last Updated: December 20, 2022
• Results First Posted: December 20, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7); HU (2); CZ (5); GB (1)