A Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) With Chronic Bronchitis (CB)

Sponsor

Ionis Pharmaceuticals, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT04441788

Collaborator

(none)

Enrollment

Locations

Arms

4.1

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Bronchitis Chronic Obstructive Pulmonary Disease	Drug: ION-827359 Drug: Placebo	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 22, 2020

Actual Primary Completion Date :

Apr 27, 2021

Actual Study Completion Date :

Apr 27, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ION-827359 Single-dose of ION-827359 will be administered by oral inhalation via nebulizer, once every week for up to 13 weeks	Drug: ION-827359 ION-827359 administered by oral inhalation
Placebo Comparator: Placebo Single-dose of placebo will be administered by oral inhalation via nebulizer, once every week for up to 13 weeks	Drug: Placebo Placebo administered by oral inhalation

Arm

Intervention/Treatment

Experimental: ION-827359

Single-dose of ION-827359 will be administered by oral inhalation via nebulizer, once every week for up to 13 weeks

Drug: ION-827359

ION-827359 administered by oral inhalation

Placebo Comparator: Placebo

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

Drug: Placebo

Placebo administered by oral inhalation

Outcome Measures

Primary Outcome Measures

Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo [From Baseline up to average of Weeks 13 and 14]

Secondary Outcome Measures

Change From Baseline in the EXACT Respiratory Symptoms (E-RS) Daily Symptom Diary to the Primary Time Point [One week prior to first dose through one week after the last dose.]
The EXACT (E-RS) scale is a participant-reported outcome (PRO) designed to measure the symptoms of participants with COPD. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms. The E-RS will be collected on the daily e-diary, which will include all 14 items from the EXACT questionnaire.
Change From Baseline in the COPD Assessment Test (CAT) to the Week 14 Time Point [From Baseline up to Week 14]
The CAT is an eight-item questionnaire that will be completed by the participant and is designed to quantify the impact of COPD symptoms on the health status of participants. The CAT provides a score of 0-40 to indicate the impact of the disease.
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) to the Week 14 Time Point [From Baseline up to Week 14]
The SGRQ is a participant completed, a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in participants with obstructive airway disease. Scores of the SGRQ-C range from 0 to 100, with higher scores indicating more limitations.
Change from Baseline in Post-Bronchodilator FEV1 [From Baseline up to average of Weeks 13 and 14]
Cmax: Maximum Observed Plasma Concentration for ION-827359 [Up to Week 24]
Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359 [Up to Week 24]
AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Time Zero to t for ION-827359 [Up to Week 24]
Incidence of Participants With at Least One Treatment-Emergent Adverse Event (TEAE), Graded by Severity [Up to Week 24]
Number of Participants With Abnormal Laboratory Values [Up to Week 24]
Number of Participants With Abnormal Vital Signs Measurements [Up to Week 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

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/m2
Patients 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:

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

Exclusion Criteria

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
Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a subject unsuitable for inclusion
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 patient (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. Patients 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)
Patients participating in, or scheduled for, an intensive (active) COPD rehabilitation program (patients who are in the maintenance phase of a rehabilitation program are eligible to take part)
Concomitant medication restrictions: Oral anticoagulants, oral steroids (e.g. prednisone or Medrol), theophylline, chronic azithromycin, or roflumilast
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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	MediTrial s.r.o.	Jindrichuv Hradec	Czechia	37701
2	Plicni ambulance Kralupy	Kralupy Nad Vltavou	Czechia	27801
3	CEFISPIRO s.r.o.	Lovosice	Czechia	410 02
4	Plicni Ambulance Rokycany, s.r.o.	Rokycany	Czechia	33701
5	PNEUMOLOGIE VARNSDORF s.r.o.	Varnsdorf	Czechia	40747
6	Pneumologisches Studienzentrum Markgrafenstrasse	Berlin	Germany	10969
7	MECS Research GmbH	Berlin	Germany	12203
8	Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH	Grosshansdorf	Germany	22927
9	Hamburger Institut far Therapieforschung GmbH	Hamburg	Germany	20354
10	KLB Gesundheitsforschung Lubeck GmbH	Lübeck	Germany	23552
11	IKF Pneumologie Mainz Helix Medical Excellence Center Mainz	Mainz	Germany	55128
12	ZMS-Zentrum fur medizinische Studien GmbH	Warendorf	Germany	48231
13	Csongrad Megyei Mellkasi Betegsegek Szakkorhaza	Deszk	Hungary	6772
14	Selye Janos Korhaz, Rendelointezet	Komarom	Hungary	2900
15	Queen Anne Street Medical Centre, Heart Lung Center	London	United Kingdom	Nw1 8HU