Phase 2a Study to Assess the Safety, Tolerability, and Efficacy of IONIS-ENaCRx in Patients with Pulmonary Disease with Chronic Bronchitis

Phase 1

• Conditions: Mild to Moderate Chronic obstructive pulmonary disease (COPD) with Chronic Bronchitis; MedDRA version: 21.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2020-000210-15-HU
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-07-30
• Last Update Posted: 17 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 180

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 (defined as 12 months of spontaneous amenorrhea without an alternative medical cause and follicle stimulating hormone (FSH) levels in the post-menopausal range for the laboratory involved). Males must be surgically sterile or abstinent*, if engaged in sexual relations with a female of child-bearing potential, the subject must be using a highly effective contraceptive method from the time of signing the informed consent form until at least 10 weeks after the last dose of Study Drug (ION-827359 or placebo):
a. * Abstinence is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception.
4. BMI < 35.0 kg/m2;
5. Patients with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS):
a. Ability to perform acceptable and reproducible spirometry;
b. 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

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:
a. 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;
b. 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;
c. alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN) > 1.5 × upper limit of normal (ULN);
d. Platelet count < LLN;
e. Serum potassium > 5.2 mmol/L;
f. Estimated GFR < 60 mL/min (as determined by the Cockcroft-Gault Equation for creatinine clearance);
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 patient (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. Active infection with human immunodeficiency virus (HIV), hepatitis C or hepatitis B;
6. Uncontrolled hypertension (blood pressure (BP) > 160/100 mm Hg);
7. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Patients with a history of other malignancies that have been treated with curative intent and which have no recurrence within 5 years may also be eligible if approved by the PI and reviewed by the Sponsor medical monitor;
8. Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer;
9. Previous treatment with an oligonucleotide (including small interfering ribonucleic acid [siRNA]) within 4 months of screening if single dose received, or within 12 months of screening if multiple doses received;
10. Clinically important pulmonary disease other than COPD;
11. 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;
12. Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 4 weeks prior to enrolment (Visit 1);
13. Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 4 weeks prior to enrolment (Visit 1);
14. Long term oxygen therapy (LTOT);
15. 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);
16. Recent history of, or current drug or alcohol abuse;
17. Concomitant medication restrictions: Oral anticoagulants, oral steroids (e.g. prednisone or Medrol), theophylline, chronic azithromycin, or roflumilast;
18. Have any other conditions, which,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified