Chronic Bronchitis, Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Bronchitis, IONIS-ENaCRx
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.
Interventions
DRUGION-827359
ION-827359 administered by oral inhalation
DRUGPlacebo
Placebo administered by oral inhalation
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point | From Baseline to Week 14 | The CAT is an eight-item questionnaire that was completed by the participant and is designed to quantify the impact of COPD symptoms on the health status of participants. Each item is rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40. Higher scores indicate a severe condition (more severe impact of COPD on a participant's life). |
| 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 | 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. The shorter 40-item version (SGRQ-C) which does not specify a Recall Period and has been validated specifically for COPD participants was used in this study. It consists of 40 items each weighted from 0 to a possible maximum of 100. Items 1-7 produced the symptoms score, 9-12 the activity score, and items 8, 10, 11, 13 and 14 the impacts score. Each component sub-score was calculated as a percentage of the summed weights of each item out of the sum of the maximum possible weight for that component (range 0-100). The total score was calculated by summing the weights to all positive responses in each component, where a positive item indicated the presence of symptoms, expressed as a percentage (range 0-100). Higher scores indicated a worse outcome (more limitations) |
| Change From Baseline in Post-Bronchodilator FEV1 | From Baseline to end of treatment (EOT) [Up to Week 14] | Post-bronchodilator FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation after administration of bronchodilator. Baseline was defined as the last non-missing measurement prior to the first study drug administration. |
| Cmax: Maximum Observed Plasma Concentration for ION-827359 | Days 1 and 85 | — |
| Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359 | Days 1 and 85 | — |
| 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 | The E-RS scale is a participant-reported outcome (PRO) designed to measure the symptoms of participants with chronic obstructive pulmonary disease (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 (comprised of 5 items, score range \[0-17\]), cough and sputum (comprised of 3 items, score range \[0-11\]), and chest symptoms (comprised of 3 items, score range \[0-12\]). The E-RS was collected on the daily e-diary. The total score was derived by summing the 11-item scores and ranged between 0 to 40 with higher values indicating severe respiratory symptoms. The primary time point was defined as the average of weeks 13 and 14. |
| Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Up to Week 24 | An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE is considered related to the medicinal (investigational) product. A TEAE is defined as any AE starting or getting worse on or after the first dose of the study drug. The severity of a TEAE was assessed by the investigator and classified into one of the following: mild, moderate, and severe. |
| Percentage of Participants With Clinically Significant Change in Laboratory Values | Up to Week 24 | Laboratory parameters for serum chemistry, hematology, urinalysis, coagulation, complement, and lipids were assessed. |
| Percentage of Participants With Clinically Significant Change in Vital Sign Parameters | Up to Week 24 | Vital signs included assessment of heart rate, blood pressure, respiratory rate, and temperature. |
| Percentage of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | Up to Week 24 | ECG parameters of ventricular rate, PR interval, QRS duration, QT, or QTc were assessed. |
| AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359 | Days 1 and 85 | — |
Countries
Czechia, Germany, Hungary, United Kingdom
Participant flow
Recruitment details
60 participants were randomized at 11 study centers in Czech Republic, Germany, Hungary and the United Kingdom.
Pre-assignment details
Of the 60 randomized participants, one was randomized but did not receive study treatment as the participant was ineligible. The study included a 2-week screening period (including a diet-stabilization period), a 12-week treatment period, and a 10-week post-treatment evaluation period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Single-dose of placebo was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. | 19 |
| ION-827359 37.5 mg Single-dose of ION-827359 37.5 mg was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. | 21 |
| 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. | 19 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 4 |
| Overall Study | Ineligibility | 1 | 0 | 0 |
| Overall Study | Study Terminated by Sponsor | 16 | 16 | 12 |
| Overall Study | Voluntary Withdrawl | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | ION-827359 37.5 mg | ION-827359 75 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 4.54 | 61.8 years STANDARD_DEVIATION 5.86 | 61.8 years STANDARD_DEVIATION 5.39 | 61.6 years STANDARD_DEVIATION 5.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 21 Participants | 19 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Forced Expiratory Volume in 1 Second (FEV1) | 1.8317 liters STANDARD_DEVIATION 0.467 | 1.9311 liters STANDARD_DEVIATION 0.6608 | 1.6536 liters STANDARD_DEVIATION 0.3498 | 1.8097 liters STANDARD_DEVIATION 0.5193 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 21 Participants | 18 Participants | 58 Participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 5 Participants | 21 Participants |
| Sex: Female, Male Male | 10 Participants | 14 Participants | 14 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 21 | 0 / 19 |
| other Total, other adverse events | 14 / 19 | 8 / 21 | 16 / 19 |
| serious Total, serious adverse events | 1 / 19 | 1 / 21 | 1 / 19 |
Outcome results
Primary
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.
Time frame: From Baseline up to average of Weeks 13 and 14
Population: FAS=all randomized participants who had ≥1 dose of study drug(ION 827359/placebo),≥1 post-Baseline efficacy assessment(i.e.,post-Baseline FEV1,Exacerbations of Chronic pulmonary Disease Tool\[EXACT\]Respiratory Symptoms\[E-RS\]score,Chronic Obstructive Pulmonary Disease\[COPD\]Assessment Test\[CAT\]score,or St.George's Respiratory Questionnaire-COPD Specific\[SGRQ-C score\],post-bronchodilator FEV1).Overall number analyzed:number of participants with data available for analyses in this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo | 0.0642 liters | Standard Deviation 0.2506 |
| ION-827359 37.5 mg | Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo | -0.0240 liters | Standard Deviation 0.3581 |
| ION-827359 75 mg | Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo | 0.1336 liters | Standard Deviation 0.1087 |
Secondary
AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359
Time frame: Days 1 and 85
Population: PK population consisted of all the participants who were randomized and received at least 1 dose of active study drug (ION-827359) and had at least 1 evaluable PK sample collected and analyzed with reportable result. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359 | Day 1 | 528 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 190 |
| Placebo | AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359 | Day 85 | 312 hours*nanogram per milliliter (h*ng/mL) | — |
| ION-827359 37.5 mg | AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359 | Day 1 | 1323 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 66 |
| ION-827359 37.5 mg | AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359 | Day 85 | 2416 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 252 |
Secondary
Change From Baseline in Post-Bronchodilator FEV1
Post-bronchodilator FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation after administration of bronchodilator. Baseline was defined as the last non-missing measurement prior to the first study drug administration.
Time frame: From Baseline to end of treatment (EOT) [Up to Week 14]
Population: FAS included all randomized participants who received at least 1 dose of study drug (ION-827359 or placebo) and who had at least 1 post-Baseline efficacy assessment (i.e., post-Baseline FEV1 assessment, E-RS score, CAT score, or SGRQ-C score). Overall number of participants analyzed is the number of participants with data available for analyses in this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Post-Bronchodilator FEV1 | 0.0663 liters | Standard Deviation 0.0685 |
| ION-827359 37.5 mg | Change From Baseline in Post-Bronchodilator FEV1 | 0.0320 liters | Standard Deviation 0.2379 |
| ION-827359 75 mg | Change From Baseline in Post-Bronchodilator FEV1 | 0.1180 liters | Standard Deviation 0.1006 |
Secondary
Change From Baseline in St. George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score to the Week 14 Time Point
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. The shorter 40-item version (SGRQ-C) which does not specify a Recall Period and has been validated specifically for COPD participants was used in this study. It consists of 40 items each weighted from 0 to a possible maximum of 100. Items 1-7 produced the symptoms score, 9-12 the activity score, and items 8, 10, 11, 13 and 14 the impacts score. Each component sub-score was calculated as a percentage of the summed weights of each item out of the sum of the maximum possible weight for that component (range 0-100). The total score was calculated by summing the weights to all positive responses in each component, where a positive item indicated the presence of symptoms, expressed as a percentage (range 0-100). Higher scores indicated a worse outcome (more limitations)
Time frame: From Baseline to Week 14
Population: FAS included all randomized participants who received at least 1 dose of study drug (ION-827359 or placebo) and who had at least 1 post-Baseline efficacy assessment (i.e., post-Baseline FEV1 assessment, E-RS score, CAT score, or SGRQ-C score). Overall number of participants analyzed is the number of participants with data available for analyses in this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in St. George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score to the Week 14 Time Point | -15.93 score on a scale | Standard Deviation 19.515 |
| ION-827359 37.5 mg | Change From Baseline in St. George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score to the Week 14 Time Point | -1.74 score on a scale | Standard Deviation 3.839 |
| ION-827359 75 mg | Change From Baseline in St. George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score to the Week 14 Time Point | -0.76 score on a scale | Standard Deviation 2.35 |
Secondary
Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point
The CAT is an eight-item questionnaire that was completed by the participant and is designed to quantify the impact of COPD symptoms on the health status of participants. Each item is rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40. Higher scores indicate a severe condition (more severe impact of COPD on a participant's life).
Time frame: From Baseline to Week 14
Population: FAS included all randomized participants who received at least 1 dose of study drug (ION-827359 or placebo) and who had at least 1 post-Baseline efficacy assessment (i.e., post-Baseline FEV1 assessment, E-RS score, CAT score, or SGRQ-C score). Overall number of participants analyzed is the number of participants with data available for analyses in this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point | -2.6 score on a scale | Standard Deviation 2.51 |
| ION-827359 37.5 mg | Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point | -0.6 score on a scale | Standard Deviation 3.78 |
| ION-827359 75 mg | Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point | 0.0 score on a scale | Standard Deviation 1.73 |
Secondary
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
The E-RS scale is a participant-reported outcome (PRO) designed to measure the symptoms of participants with chronic obstructive pulmonary disease (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 (comprised of 5 items, score range \[0-17\]), cough and sputum (comprised of 3 items, score range \[0-11\]), and chest symptoms (comprised of 3 items, score range \[0-12\]). The E-RS was collected on the daily e-diary. The total score was derived by summing the 11-item scores and ranged between 0 to 40 with higher values indicating severe respiratory symptoms. The primary time point was defined as the average of weeks 13 and 14.
Time frame: From Baseline up to average of weeks 13 and 14
Population: FAS included all randomized participants who received at least 1 dose of study drug (ION-827359 or placebo) and who had at least 1 post-Baseline efficacy assessment (i.e., post-Baseline FEV1 assessment, E-RS score, CAT score, or SGRQ-C score). Overall number of participants analyzed is the number of participants with data available for analyses in this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | -1.08 score on a scale | Standard Deviation 1.171 |
| ION-827359 37.5 mg | 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 | -1.41 score on a scale | Standard Deviation 2.486 |
| ION-827359 75 mg | 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 | -1.99 score on a scale | Standard Deviation 4.217 |
Secondary
Cmax: Maximum Observed Plasma Concentration for ION-827359
Time frame: Days 1 and 85
Population: Pharmacokinetic (PK) population included all participants who were randomized and received at least 1 dose of active study drug (ION-827359) and had at least 1 evaluable PK sample collected and analyzed with reportable result. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax: Maximum Observed Plasma Concentration for ION-827359 | Day 1 | 85.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 198 |
| Placebo | Cmax: Maximum Observed Plasma Concentration for ION-827359 | Day 85 | 53.5 nanogram per milliliter (ng/mL) | — |
| ION-827359 37.5 mg | Cmax: Maximum Observed Plasma Concentration for ION-827359 | Day 1 | 203 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 52.6 |
| ION-827359 37.5 mg | Cmax: Maximum Observed Plasma Concentration for ION-827359 | Day 85 | 195 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 124 |
Secondary
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity
An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE is considered related to the medicinal (investigational) product. A TEAE is defined as any AE starting or getting worse on or after the first dose of the study drug. The severity of a TEAE was assessed by the investigator and classified into one of the following: mild, moderate, and severe.
Time frame: Up to Week 24
Population: Safety population included all participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Moderate | 52.6 percentage of participants |
| Placebo | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Mild | 10.5 percentage of participants |
| Placebo | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Severe | 10.5 percentage of participants |
| ION-827359 37.5 mg | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Moderate | 38.1 percentage of participants |
| ION-827359 37.5 mg | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Mild | 14.3 percentage of participants |
| ION-827359 37.5 mg | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Severe | 0 percentage of participants |
| ION-827359 75 mg | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Mild | 15.8 percentage of participants |
| ION-827359 75 mg | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Severe | 5.3 percentage of participants |
| ION-827359 75 mg | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity | Moderate | 63.2 percentage of participants |
Secondary
Percentage of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
ECG parameters of ventricular rate, PR interval, QRS duration, QT, or QTc were assessed.
Time frame: Up to Week 24
Population: Safety population included all participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | 0 percentage of participants |
| ION-827359 37.5 mg | Percentage of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | 0 percentage of participants |
| ION-827359 75 mg | Percentage of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | 0 percentage of participants |
Secondary
Percentage of Participants With Clinically Significant Change in Laboratory Values
Laboratory parameters for serum chemistry, hematology, urinalysis, coagulation, complement, and lipids were assessed.
Time frame: Up to Week 24
Population: Safety population included all participants who are were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Clinically Significant Change in Laboratory Values | 0 percentage of participants |
| ION-827359 37.5 mg | Percentage of Participants With Clinically Significant Change in Laboratory Values | 0 percentage of participants |
| ION-827359 75 mg | Percentage of Participants With Clinically Significant Change in Laboratory Values | 0 percentage of participants |
Secondary
Percentage of Participants With Clinically Significant Change in Vital Sign Parameters
Vital signs included assessment of heart rate, blood pressure, respiratory rate, and temperature.
Time frame: Up to Week 24
Population: Safety population included all participants who are were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Clinically Significant Change in Vital Sign Parameters | 0 percentage of participants |
| ION-827359 37.5 mg | Percentage of Participants With Clinically Significant Change in Vital Sign Parameters | 0 percentage of participants |
| ION-827359 75 mg | Percentage of Participants With Clinically Significant Change in Vital Sign Parameters | 0 percentage of participants |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359
Time frame: Days 1 and 85
Population: PK population included all participants who were randomized and received at least 1 dose of active study drug (ION-827359) and had at least 1 evaluable PK sample collected and analyzed with reportable result. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359 | Day 1 | 1.54 hours |
| Placebo | Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359 | Day 85 | 1.98 hours |
| ION-827359 37.5 mg | Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359 | Day 1 | 1.64 hours |
| ION-827359 37.5 mg | Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359 | Day 85 | 3.11 hours |