| Primary | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | 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. | Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo). | Posted | | Count of Participants | | Participants | | Up to Day 176 | | | | ID | Title | Description |
|---|
| OG000 | Multiple Dose Cohort: Placebo | 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. | | OG001 | 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. | | OG002 | 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. | | OG003 | 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. | | OG004 | 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. | | OG005 | 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. |
| | Units | Counts |
|---|
| Participants | - OG0006
- OG00110
- OG00210
- OG003
|
| | Title | Denominators | Categories |
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| | |
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| Primary | Percentage of Participants Using Concomitant Medications | 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. | Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo). | Posted | | Number | | percentage of participants | | Up to Day 176 | | | | ID | Title | Description |
|---|
| OG000 | Multiple Dose Cohort: Placebo | 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. | | OG001 | 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. | | OG002 | 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. |
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| Primary | Number of Participants With Clinically Significant Laboratory Values | 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. | Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo). | Posted | | Count of Participants | | Participants | | Up to Day 176 | | | | ID | Title | Description |
|---|
| OG000 | Multiple Dose Cohort: Placebo | 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. | | OG001 | 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. | | OG002 | Multiple Dose Cohort E: ION-682884 60 mg | |
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| Primary | Number of Participants With Clinically Significant Physical Examination Findings | 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. | Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo). | Posted | | Count of Participants | | Participants | | Up to Day 176 | | | | ID | Title | Description |
|---|
| OG000 | Multiple Dose Cohort: Placebo | 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. | | OG001 | 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. | | OG002 | 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. |
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| Primary | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | 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. | Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo). | Posted | | Count of Participants | | Participants | | Up to Day 176 | | | | ID | Title | Description |
|---|
| OG000 | Multiple Dose Cohort: Placebo | 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. | | OG001 | 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. | | OG002 | Multiple Dose Cohort E: ION-682884 60 mg |
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| Secondary | Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | micrograms per milliters (µg/mL) | | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | 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. | |
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| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx | | 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. | Posted | | Median | Full Range | hours | | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | 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. | | OG003 |
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| Secondary | AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | micrograms*hour per milliliter (µg*h/mL) | | 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 C | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | 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. |
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| Secondary | CL/F: Apparent Total Clearance of ION-TTR-LRx | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | liters per hour (L/h) | | 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 C | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | 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. | |
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| Secondary | t1/2λz: Termination Half-Life of ION-TTR-LRx | | 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. | Posted | | Median | Full Range | days | | Up to 92 hours; post-dose on Day 85 for Cohorts A, B, and E, and on Day 1 for Cohort C | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | 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. | | OG003 | Single Dose Cohort C: ION-682884 120 mg |
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| Secondary | Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | micrograms (μg) | | From 0 to 24 hours post-dose on Days 1 and 85 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | 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. | | OG003 |
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| Secondary | Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx | | 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. | Posted | | Mean | Standard Deviation | milligrams per deciliters (mg/dL) | | Baseline, Days 29 and 99 | | | | ID | Title | Description |
|---|
| OG000 | Multiple Dose Cohort: Placebo | 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. | | OG001 | 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. | | OG002 | 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. | | OG003 |
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| Secondary | Change From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx | | 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. | Posted | | Mean | Standard Deviation | micrograms per milliliters (µg/mL) | | Baseline, Days 29 and 99 | | | | ID | Title | Description |
|---|
| OG000 | Multiple Dose Cohort: Placebo | 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. | | OG001 | 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. | | OG002 | 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. | | OG003 |
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| Secondary | Percent Abundance of ION-682884 Antisense Oligonucleotide (ASO) Species (Metabolite) Following Administration of ION-682884 90 mg | As prespecified in the protocol, this outcome measure was planned to be analyzed only in the Multiple Dose Cohort B: 90 mg ION-682884. | 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. | Posted | | Mean | Standard Deviation | percent abundance of ION-682884 ASO | | 2 hours post-dose on Day 85 | | | | ID | Title | Description |
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| OG000 | 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. |
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