Trial Outcomes & Findings for Evaluate the Safety and Tolerability, as Well as the Pharmacokinetic and Pharmacodynamic Profiles of Single and Multiple Doses of Eplontersen Administered Subcutaneously to Healthy Volunteers and Patients With Hereditary Transthyretin-Mediated Amyloidosis (hATTR ). (NCT NCT03728634)
NCT ID: NCT03728634
Last Updated: 2022-12-19
Results Overview
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of study drug and subsequently worsened or was not present prior to receiving the first dose of study drug but subsequently appeared.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
47 participants
Primary outcome timeframe
Up to Day 176
Results posted on
2022-12-19
Participant Flow
A total of 47 participants were enrolled, of which 36 were randomized in multiple-dose cohorts and 11 in single-dose cohorts. This study consisted of a single-dose on Day 1, and 13 weeks of Post-Treatment Follow-up for participants in Cohort C and a 12-week Treatment Period followed by 13-week Post Treatment Evaluation Period for participants in Cohorts A, B, and E. Due to limited number of suitable participants with hereditary transthyretin amyloidosis (hATTR), Cohort D was never initiated.
Participant milestones
| Measure |
Multiple Dose Cohort: Placebo
Participants received ION-682884 matching placebo, subcutaneously (SC), once every 4 weeks \[Q4W\] (total of 4 doses) along with daily oral supplemental doses of the recommended daily allowance (RDA) of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
10
|
10
|
10
|
2
|
9
|
|
Overall Study
COMPLETED
|
6
|
10
|
10
|
10
|
2
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluate the Safety and Tolerability, as Well as the Pharmacokinetic and Pharmacodynamic Profiles of Single and Multiple Doses of Eplontersen Administered Subcutaneously to Healthy Volunteers and Patients With Hereditary Transthyretin-Mediated Amyloidosis (hATTR ).
Baseline characteristics by cohort
| Measure |
Multiple Dose Cohort: Placebo
n=6 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=10 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
n=2 Participants
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
n=9 Participants
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
49.2 years
n=5 Participants
|
51.6 years
n=7 Participants
|
51.6 years
n=5 Participants
|
51.1 years
n=4 Participants
|
57.0 years
n=21 Participants
|
43.4 years
n=10 Participants
|
49.84 years
n=115 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
20 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
8 Participants
n=10 Participants
|
27 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
9 Participants
n=10 Participants
|
47 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
11 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
11 Participants
n=115 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
25 Participants
n=115 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: Up to Day 176Population: Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo).
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of study drug and subsequently worsened or was not present prior to receiving the first dose of study drug but subsequently appeared.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=6 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=10 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
n=2 Participants
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
n=9 Participants
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
|
3 Participants
|
1 Participants
|
3 Participants
|
7 Participants
|
1 Participants
|
4 Participants
|
PRIMARY outcome
Timeframe: Up to Day 176Population: Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo).
A concomitant therapy was any non-protocol-specified drug or substance (including over-the-counter \[OTC\] medications, herbal medications, and vitamin supplements) administered between signing of informed consent and the last study visit.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=6 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=10 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
n=2 Participants
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
n=9 Participants
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Using Concomitant Medications
|
0.0 percentage of participants
|
0.0 percentage of participants
|
30.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
22.2 percentage of participants
|
PRIMARY outcome
Timeframe: Up to Day 176Population: Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo).
Laboratory parameters included measurement of blood chemistry, hematology, coagulation, complement, or urinalysis parameters for the single-dose and multiple-dose cohorts. Number of participants with clinically significant values in laboratory based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=6 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=10 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
n=2 Participants
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
n=9 Participants
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Laboratory Values
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Day 176Population: Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo).
Physical examination included measurement of height and weight for body mass index (BMI) determination. Number of participants with clinically significant findings in physical examination based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=6 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=10 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
n=2 Participants
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
n=9 Participants
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Physical Examination Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Day 176Population: Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo).
ECG measurements included assessment of ventricular rate (VR), PR interval, QR interval, QT interval, QT corrected using Fridericia's formula (QTcF), and QT corrected using Bazett's formula (QTcB). Number of participants with clinically significant values in electrocardiogram based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=6 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=10 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
n=2 Participants
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
n=9 Participants
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Values
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85Population: Pharmacokinetic (PK) Set included all participants who were randomized, received at least 1 dose of ION-682884, and had at least 1 evaluable PK sample. Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=10 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=9 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx
Day 1
|
0.143 micrograms per milliters (µg/mL)
Geometric Coefficient of Variation 39.3
|
0.239 micrograms per milliters (µg/mL)
Geometric Coefficient of Variation 62.6
|
0.332 micrograms per milliters (µg/mL)
Geometric Coefficient of Variation 43.6
|
0.542 micrograms per milliters (µg/mL)
Geometric Coefficient of Variation 65.0
|
—
|
—
|
|
Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx
Day 85
|
0.215 micrograms per milliters (µg/mL)
Geometric Coefficient of Variation 66.1
|
0.282 micrograms per milliters (µg/mL)
Geometric Coefficient of Variation 74.5
|
0.471 micrograms per milliters (µg/mL)
Geometric Coefficient of Variation 69.5
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85Population: PK Set included all participants who were randomized, received at least 1 dose of ION-682884, and had at least 1 evaluable PK sample. Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=10 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=9 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx
Day 1
|
2.01 hours
Interval 1.0 to 4.0
|
6.00 hours
Interval 3.0 to 12.0
|
2.25 hours
Interval 1.0 to 6.0
|
4.00 hours
Interval 1.0 to 8.0
|
—
|
—
|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx
Day 85
|
3.00 hours
Interval 1.0 to 3.0
|
1.00 hours
Interval 1.0 to 3.0
|
3.00 hours
Interval 1.0 to 8.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From 0 to 672 hours post-dose on Day 85 for Cohorts A, B, and E; 0 hours to extrapolation to infinity post-dose on Day 1 for Cohort CPopulation: PK Set included all participants who were randomized, received at least 1 dose of ION-682884, and had at least 1 evaluable PK sample. Overall number analyzed are the number of participants with data available for analyses.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=10 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=7 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx
Day 1
|
—
|
—
|
—
|
6.78 micrograms*hour per milliliter (µg*h/mL)
Geometric Coefficient of Variation 20.3
|
—
|
—
|
|
AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx
Day 85
|
1.81 micrograms*hour per milliliter (µg*h/mL)
Geometric Coefficient of Variation 36.3
|
2.73 micrograms*hour per milliliter (µg*h/mL)
Geometric Coefficient of Variation 43.2
|
4.35 micrograms*hour per milliliter (µg*h/mL)
Geometric Coefficient of Variation 43.2
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From 0 to 672 hours post-dose on Day 85 for Cohorts A, B, and E; 0 hours to extrapolation to infinity post-dose on Day 1 for Cohort CPopulation: PK Set included all participants who were randomized, received at least 1 dose of ION-682884, and had at least 1 evaluable PK sample. Overall number analyzed are the number of participants with data available for analyses.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=10 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=7 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
CL/F: Apparent Total Clearance of ION-TTR-LRx
Day 1
|
—
|
—
|
—
|
17.7 liters per hour (L/h)
Geometric Coefficient of Variation 20.3
|
—
|
—
|
|
CL/F: Apparent Total Clearance of ION-TTR-LRx
Day 85
|
24.8 liters per hour (L/h)
Geometric Coefficient of Variation 36.3
|
22.0 liters per hour (L/h)
Geometric Coefficient of Variation 43.2
|
20.7 liters per hour (L/h)
Geometric Coefficient of Variation 43.2
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 92 hours; post-dose on Day 85 for Cohorts A, B, and E, and on Day 1 for Cohort CPopulation: PK Set included all participants who were randomized, received at least 1 dose of ION-682884, and had at least 1 evaluable PK sample. Number analyzed is the number of participants with data available for analysis at the given timepoint.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=6 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=8 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=8 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=7 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
t1/2λz: Termination Half-Life of ION-TTR-LRx
Day 1
|
—
|
—
|
—
|
17.9 days
Interval 12.8 to 40.7
|
—
|
—
|
|
t1/2λz: Termination Half-Life of ION-TTR-LRx
Day 85
|
22.3 days
Interval 10.3 to 52.7
|
30.3 days
Interval 20.1 to 58.9
|
24.8 days
Interval 15.2 to 45.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From 0 to 24 hours post-dose on Days 1 and 85Population: PK Set included all participants who were randomized, received at least 1 dose of ION-682884, and had at least 1 evaluable PK sample. Number analyzed is the number of participants with data available for analysis at the given timepoint.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=10 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=9 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period
Day 1
|
17.0 micrograms (μg)
Geometric Coefficient of Variation 54.1
|
23.5 micrograms (μg)
Geometric Coefficient of Variation 62.3
|
29.9 micrograms (μg)
Geometric Coefficient of Variation 146
|
87.4 micrograms (μg)
Geometric Coefficient of Variation 87.9
|
—
|
—
|
|
Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period
Day 85
|
40.6 micrograms (μg)
Geometric Coefficient of Variation 38.0
|
68.3 micrograms (μg)
Geometric Coefficient of Variation 57.2
|
133 micrograms (μg)
Geometric Coefficient of Variation 33.8
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Days 29 and 99Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo). Number analyzed is the number of participants with data available for analysis at the given timepoint.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=6 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=10 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
n=2 Participants
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
n=9 Participants
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx
Day 29
|
-0.225 milligrams per deciliters (mg/dL)
Standard Deviation 2.935
|
-13.40 milligrams per deciliters (mg/dL)
Standard Deviation 4.312
|
-18.63 milligrams per deciliters (mg/dL)
Standard Deviation 4.933
|
-19.42 milligrams per deciliters (mg/dL)
Standard Deviation 5.441
|
0.725 milligrams per deciliters (mg/dL)
Standard Deviation 1.732
|
-20.06 milligrams per deciliters (mg/dL)
Standard Deviation 3.615
|
|
Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx
Day 99
|
0.908 milligrams per deciliters (mg/dL)
Standard Deviation 4.050
|
-18.60 milligrams per deciliters (mg/dL)
Standard Deviation 2.911
|
-22.02 milligrams per deciliters (mg/dL)
Standard Deviation 3.564
|
-21.91 milligrams per deciliters (mg/dL)
Standard Deviation 5.175
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Days 29 and 99Population: FAS included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo). Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=6 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 Participants
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 Participants
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=10 Participants
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
n=2 Participants
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
n=9 Participants
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx
Day 99
|
171 micrograms per milliliters (µg/mL)
Standard Deviation 4311
|
-28693 micrograms per milliliters (µg/mL)
Standard Deviation 6132
|
-20124 micrograms per milliliters (µg/mL)
Standard Deviation 3946
|
-25365 micrograms per milliliters (µg/mL)
Standard Deviation 7275
|
—
|
—
|
|
Change From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx
Day 29
|
69 micrograms per milliliters (µg/mL)
Standard Deviation 5404
|
-19317 micrograms per milliliters (µg/mL)
Standard Deviation 8459
|
-16383 micrograms per milliliters (µg/mL)
Standard Deviation 5191
|
-21961 micrograms per milliliters (µg/mL)
Standard Deviation 8264
|
1786 micrograms per milliliters (µg/mL)
Standard Deviation 623
|
-24765 micrograms per milliliters (µg/mL)
Standard Deviation 7020
|
SECONDARY outcome
Timeframe: 2 hours post-dose on Day 85Population: PK Set included all participants who were randomized, received at least 1 dose of ION-682884, and had at least 1 evaluable PK sample. As prespecified in the protocol, this outcome measure was planned to be analyzed in healthy participants administered with 90 mg ION-682884 Q4W for 13 weeks i.e., in the Multiple Dose Cohort B: 90 mg ION-682884.
As prespecified in the protocol, this outcome measure was planned to be analyzed only in the Multiple Dose Cohort B: 90 mg ION-682884.
Outcome measures
| Measure |
Multiple Dose Cohort: Placebo
n=10 Participants
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
Participants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Percent Abundance of ION-682884 Antisense Oligonucleotide (ASO) Species (Metabolite) Following Administration of ION-682884 90 mg
|
99.1 percent abundance of ION-682884 ASO
Standard Deviation 1.19
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Multiple Dose Cohort: Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Multiple Dose Cohort A: ION-682884 45 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Multiple Dose Cohort E: ION-682884 60 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Multiple Dose Cohort B: ION-682884 90 mg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Single Dose Cohort: Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Single Dose Cohort C: ION-682884 120 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Multiple Dose Cohort: Placebo
n=6 participants at risk
Participants received ION-682884 matching placebo, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort A: ION-682884 45 mg
n=10 participants at risk
Participants received ION-682884, 45 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort E: ION-682884 60 mg
n=10 participants at risk
Participants received ION-682884, 60 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Multiple Dose Cohort B: ION-682884 90 mg
n=10 participants at risk
Participants received ION-682884, 90 mg, SC, Q4W (total of 4 doses) along with daily oral supplemental doses of the RDA of vitamin A during the 13-week Treatment Period.
|
Single Dose Cohort: Placebo
n=2 participants at risk
Participants received single dose of ION-682884 matching placebo, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
Single Dose Cohort C: ION-682884 120 mg
n=9 participants at risk
Participants received single dose of ION-682884,120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.
|
|---|---|---|---|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
40.0%
4/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Investigations
Blood creatine phosphokinase increased
|
16.7%
1/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
40.0%
4/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Investigations
Weight increased
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
10.0%
1/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
General disorders
Injection site bruising
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
10.0%
1/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
General disorders
Injection site erythema
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
10.0%
1/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
General disorders
Injection site reaction
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
10.0%
1/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
General disorders
Injection site swelling
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
10.0%
1/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
General disorders
Vessel puncture site bruise
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
10.0%
1/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
General disorders
Vessel puncture site paraesthesia
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
10.0%
1/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
10.0%
1/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
10.0%
1/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
1/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
22.2%
2/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
11.1%
1/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
11.1%
1/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
11.1%
1/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
11.1%
1/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
General disorders
Influenza like illness
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
11.1%
1/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
General disorders
Malaise
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
11.1%
1/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
0.00%
0/6 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/10 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
50.0%
1/2 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
0.00%
0/9 • Up to Day 176
Safety Set included all randomized participants who received at least 1 injection of study drug (ION-682884 or placebo).
|
Additional Information
Ionis Pharmaceuticals, Inc.
Ionis Pharmaceuticals, Inc.
Phone: 800-679-4747
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER