Mild to Moderate Chronic obstructive pulmonary disease (COPD) with Chronic Bronchitis MedDRA version: 21.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Interventions
Product Name: antisense inhibitor of ENaC
Product Code: ION-827359
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: ION-827359
CAS Number: 2247669-97-0
Current Sponsor code: ION-827359
O
Sponsors
Ionis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion 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 (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 condom in addition to a highly effective contraceptive method by the partner 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 =65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
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 1.5 × upper limit of normal (ULN); d. Platelet count 5.2 mmol/L; f. Estimated GFR 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,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of IONIS-ENaCRx on forced expiratory volume in 1 second (FEV1) in patients with mild to moderate chronic obstructive pulmonary disease (COPD) with chronic bronchitis (CB).;Secondary Objective: - To evaluate the effect of IONIS-ENaCRx on symptoms of CB; - To evaluate the effect of IONIS-ENaCRx on quality of life (QoL)in patients of CB; - To evaluate the pharmacokinetics (PK) of IONIS-ENaCRx in patients with CB; - To evaluate the safety and tolerability of IONIS-ENaCRx compared to placebo.;Primary end point(s): Change from baseline to the primary time point (defined as the average of Weeks 13 and 14) in FEV1 compared to placebo;Timepoint(s) of evaluation of this end point: Average of Weeks 13 and 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in the EXACT respiratory symptoms (E-RS) (evaluating respiratory symptoms) daily symptom diary to the primary time point - Change from baseline in the COPD assessment test (CAT) to the Week 14 time point - Change from baseline in St. George’s Respiratory Questionnaire (SGRQ) to the Week 14 time point - Change from baseline in post-bronchodilator FEV1 - Pharmacokinetics (Section 1.2.3.1) - Safety Secondary Endpoints - Incidence and severity of treatment-emergent adverse events (TEAE) - Abnormal findings in laboratory assessments, electrocardiogram (ECGs), and vital signs;Timepoint(s) of evaluation of this end point: Up to 13 weeks | — |
Countries
Czechia, Czech Republic, Germany, Hungary, Italy, Poland, Spain, United Kingdom
Contacts
Public ContactIonis Clinical Trial
Ionis Pharmaceuticals, Inc.
Outcome results
None listed