Healthy VolunteersPhase 1/2NCT03728634

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 ).

A Phase 1/2 study testing ION-682884 and Vitamin A in people with Healthy Volunteers and hATTR Amyloidosis, run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To 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 ). Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers, hATTR Amyloidosis
What is being tested?: ION-682884 and Vitamin A
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 47 participants
Where: 1 siteCanada
Study dates: 21 Dec 2018to 20 Feb 2020
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Aged 18 to 82 years at the time of informed consent
Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method
Diagnosis of hereditary transthyretin-mediated polyneuropathy
BMI > 16 kg/m2

Who cannot join

Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to abnormal safety labs
Karnofsky performance status ≤ 50
Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes
Prior liver transplant or anticipated liver transplant within 1-yr of Screening
New York Heart Association (NYHA) functional classification of ≥ 3
Acute coronary syndrome or major surgery within 3 months of Screening
Other types of amyloidosis
Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

Trial locations and contacts

1 site in 1 country.

Canada1 site

Bio Pharma Services, Inc.
Toronto, Ontario, M9L 3A2

Other trials in Canada

About this study

Official title: This Was a Phase 1/2, Double-blind, Randomized, Placebo-controlled, Dose-escalation Study Conducted at a Single Center for the Healthy Volunteer Cohorts in up to 56 Participants. It Consisted of 1 Single-dose Cohort and 3 Multiple-dose Cohorts (n = 12 Per Cohort, 10 Active:2 Placebo). The Open-label, hATTR Patient Cohort Portion of the Study Was Conducted at Multiple Centers.

Read the detailed description

This will be a Phase 1/2, double-blind, randomized, placebo-controlled, dose-escalation study conducted at a single center for the healthy volunteer cohorts in up to 56 participants. It will consist of 1 single-dose cohort and 3 multiple-dose cohorts (n = 12 per cohort, 10 active:2 placebo). The open-label, hATTR patient cohort portion of the study will be conducted at multiple centers.

Conditions: Healthy Volunteers, hATTR Amyloidosis
Being tested: ION-682884, Placebo, Vitamin A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ION-682884Drug
Also called Eplontersen, AKCEA-TTR-LRx, IONIS-TTR-LRx
ION-682884 administered SC
PlaceboDrug
Placebo comparator calculated volume to match ION-682884 administered SC
Vitamin ADietary supplement
Oral supplement

Study groups in NCT03728634
Study group	Role	What they receive
Multiple Dose Cohort: Placebo	Placebo comparator	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. Receives: Drug: Placebo; Dietary Supplement: Vitamin A
Multiple Dose Cohort A: ION-682884 45 mg	Experimental	Participants received ION-682884, 45 milligrams (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. Receives: Drug: ION-682884; Dietary Supplement: Vitamin A
Multiple Dose Cohort E: ION-682884 60 mg	Experimental	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. Receives: Drug: ION-682884; Dietary Supplement: Vitamin A
Multiple Dose Cohort B: ION-682884 90 mg	Experimental	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. Receives: Drug: ION-682884; Dietary Supplement: Vitamin A
Single Dose Cohort: Placebo	Placebo comparator	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. Receives: Drug: Placebo; Dietary Supplement: Vitamin A
Single Dose Cohort C: ION-682884 120 mg	Experimental	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. Receives: Drug: ION-682884; Dietary Supplement: Vitamin A

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to Day 176
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.
Measured: Up to Day 176
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.
Measured: Up to Day 176
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.
Measured: Up to Day 176
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.
Measured: Up to Day 176

Secondary outcomes (9)

Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx
Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx
Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85
AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx
Measured: 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
CL/F: Apparent Total Clearance of ION-TTR-LRx
Measured: 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
t1/2λz: Termination Half-Life of ION-TTR-LRx
Measured: Up to 92 hours; post-dose on Day 85 for Cohorts A, B, and E, and on Day 1 for Cohort C
Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period
Measured: From 0 to 24 hours post-dose on Days 1 and 85
Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx
Measured: Baseline, Days 29 and 99
Change From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx
Measured: Baseline, Days 29 and 99
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.
Measured: 2 hours post-dose on Day 85

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Dec 201820 Feb 2020

First posted2 Nov 2018
Study start21 Dec 2018
Primary completion20 Feb 2020
Study completion20 Feb 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03728634
Sponsor's protocol ID: ION-682884-CS1
Status last verified: Nov 2022
First submitted: 31 Oct 2018
Last updated: 19 Dec 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Diep JK, Yu RZ, Viney NJ, Schneider E, Guo S, Henry S, Monia B, Geary R, Wang Y. Population pharmacokinetic/pharmacodynamic modelling of eplontersen, an antisense oligonucleotide in development for transthyretin amyloidosis. Br J Clin Pharmacol. 2022 Dec;88(12):5389-5398. doi: 10.1111/bcp.15468. Epub 2022 Aug 7.
PubMed 35869634
Viney NJ, Guo S, Tai LJ, Baker BF, Aghajan M, Jung SW, Yu RZ, Booten S, Murray H, Machemer T, Burel S, Murray S, Buchele G, Tsimikas S, Schneider E, Geary RS, Benson MD, Monia BP. Ligand conjugated antisense oligonucleotide for the treatment of transthyretin amyloidosis: preclinical and phase 1 data. ESC Heart Fail. 2021 Feb;8(1):652-661. doi: 10.1002/ehf2.13154. Epub 2020 Dec 7.
PubMed 33283485

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: This Was a Phase 1/2, Double-blind, Randomized, Placebo-controlled, Dose-escalation Study Conducted at a Single Center for the Healthy Volunteer Cohorts in up to 56 Participants. It Consisted of 1 Single-dose Cohort and 3 Multiple-dose Cohorts (n = 12 Per Cohort, 10 Active:2 Placebo). The Open-label, hATTR Patient Cohort Portion of the Study Was Conducted at Multiple Centers.
ClinicalTrials.gov ID: NCT03728634
Acronym / sponsor ID: ION-682884-CS1
Conditions: Healthy Volunteers, hATTR Amyloidosis
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 47 participants (actual)
Lead sponsor: Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 21 Dec 2018 (actual)
Primary completion: 20 Feb 2020 (actual)
Study completion: 20 Feb 2020 (actual)
First posted: 2 Nov 2018 (actual)
Results: Posted 19 Dec 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
Multiple Dose Cohort: Placebo	Placebo comparator	Drug: Placebo, Dietary Supplement: Vitamin AParticipants 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	Experimental	Drug: ION-682884, Dietary Supplement: Vitamin AParticipants received ION-682884, 45 milligrams (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	Experimental	Drug: ION-682884, Dietary Supplement: Vitamin AParticipants 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	Experimental	Drug: ION-682884, Dietary Supplement: Vitamin AParticipants 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	Placebo comparator	Drug: Placebo, Dietary Supplement: Vitamin AParticipants 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	Experimental	Drug: ION-682884, Dietary Supplement: Vitamin AParticipants received single dose of ION-682884, 120 mg, SC along with daily oral supplemental doses of the RDA of vitamin A on Day 1.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Aged 18 to 82 years at the time of informed consent
Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method
Diagnosis of hereditary transthyretin-mediated polyneuropathy
BMI > 16 kg/m2

Key exclusion criteria (8 listed)

Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to abnormal safety labs
Karnofsky performance status ≤ 50
Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes
Prior liver transplant or anticipated liver transplant within 1-yr of Screening
New York Heart Association (NYHA) functional classification of ≥ 3

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ION-682884Also: Eplontersen, AKCEA-TTR-LRx, IONIS-TTR-LRxION-682884 administered SC	Drug	Multiple Dose Cohort A: ION-682884 45 mg, Multiple Dose Cohort B: ION-682884 90 mg, Multiple Dose Cohort E: ION-682884 60 mg, Single Dose Cohort C: ION-682884 120 mg
PlaceboPlacebo comparator calculated volume to match ION-682884 administered SC	Drug	Multiple Dose Cohort: Placebo, Single Dose Cohort: Placebo
Vitamin AOral supplement	Dietary supplement	Multiple Dose Cohort A: ION-682884 45 mg, Multiple Dose Cohort B: ION-682884 90 mg, Multiple Dose Cohort E: ION-682884 60 mg, Multiple Dose Cohort: Placebo, Single Dose Cohort C: ION-682884 120 mg, Single Dose Cohort: Placebo

Primary outcome

Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
Time frame: Up to Day 176
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.
Percentage of Participants Using Concomitant Medications
Time frame: Up to Day 176
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.
Number of Participants With Clinically Significant Laboratory Values
Time frame: Up to Day 176
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.
Number of Participants With Clinically Significant Physical Examination Findings
Time frame: Up to Day 176
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.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Values
Time frame: Up to Day 176
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.

9 secondary outcomes

Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85
AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx
Time frame: 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
CL/F: Apparent Total Clearance of ION-TTR-LRx
Time frame: 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
t1/2λz: Termination Half-Life of ION-TTR-LRx
Time frame: Up to 92 hours; post-dose on Day 85 for Cohorts A, B, and E, and on Day 1 for Cohort C
Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period
Time frame: From 0 to 24 hours post-dose on Days 1 and 85
Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx
Time frame: Baseline, Days 29 and 99
Change From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx
Time frame: Baseline, Days 29 and 99
Percent Abundance of ION-682884 Antisense Oligonucleotide (ASO) Species (Metabolite) Following Administration of ION-682884 90 mg
Time frame: 2 hours post-dose on Day 85

Results and safety

Results posted to the registry on 19 Dec 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Multiple Dose Cohort: Placebo	6	6
Multiple Dose Cohort A: ION-682884 45 mg	10	10
Multiple Dose Cohort E: ION-682884 60 mg	10	10
Multiple Dose Cohort B: ION-682884 90 mg	10	10
Single Dose Cohort: Placebo	2	2
Single Dose Cohort C: ION-682884 120 mg	9	9

Primary outcome: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)

Time frame: Up to Day 176. Count of participants. Unit: Participants

Measure	Multiple Dose Cohort: Placebo n = 6	Multiple Dose Cohort A: ION-682884 45 mg n = 10	Multiple Dose Cohort E: ION-682884 60 mg n = 10	Multiple Dose Cohort B: ION-682884 90 mg n = 10	Single Dose Cohort: Placebo n = 2	Single Dose Cohort C: ION-682884 120 mg n = 9
Value	3	1	3	7	1	4

Population analysed: Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo).

Primary outcome: Percentage of Participants Using Concomitant Medications

Time frame: Up to Day 176. Number. Unit: percentage of participants

Measure	Multiple Dose Cohort: Placebo n = 6	Multiple Dose Cohort A: ION-682884 45 mg n = 10	Multiple Dose Cohort E: ION-682884 60 mg n = 10	Multiple Dose Cohort B: ION-682884 90 mg n = 10	Single Dose Cohort: Placebo n = 2	Single Dose Cohort C: ION-682884 120 mg n = 9
Value	0.0	0.0	30.0	0.0	0.0	22.2

Population analysed: Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo).

Primary outcome: Number of Participants With Clinically Significant Laboratory Values

Time frame: Up to Day 176. Count of participants. Unit: Participants

Measure	Multiple Dose Cohort: Placebo n = 6	Multiple Dose Cohort A: ION-682884 45 mg n = 10	Multiple Dose Cohort E: ION-682884 60 mg n = 10	Multiple Dose Cohort B: ION-682884 90 mg n = 10	Single Dose Cohort: Placebo n = 2	Single Dose Cohort C: ION-682884 120 mg n = 9
Value	0	0	0	0	0	0

Population analysed: Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo).

Primary outcome: Number of Participants With Clinically Significant Physical Examination Findings

Time frame: Up to Day 176. Count of participants. Unit: Participants

Measure	Multiple Dose Cohort: Placebo n = 6	Multiple Dose Cohort A: ION-682884 45 mg n = 10	Multiple Dose Cohort E: ION-682884 60 mg n = 10	Multiple Dose Cohort B: ION-682884 90 mg n = 10	Single Dose Cohort: Placebo n = 2	Single Dose Cohort C: ION-682884 120 mg n = 9
Value	0	0	0	0	0	0

Population analysed: Safety Set included all randomized participants who receive at least 1 injection of study drug (ION-682884 or placebo).

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Day 176. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Multiple Dose Cohort: Placebo	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Multiple Dose Cohort A: ION-682884 45 mg	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Multiple Dose Cohort E: ION-682884 60 mg	0 of 10 (0%)	3 of 10 (30%)	0 of 10
Multiple Dose Cohort B: ION-682884 90 mg	0 of 10 (0%)	7 of 10 (70%)	0 of 10
Single Dose Cohort: Placebo	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Single Dose Cohort C: ION-682884 120 mg	0 of 9 (0%)	4 of 9 (44.4%)	0 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35869634Diep JK, Yu RZ, Viney NJ, Schneider E, Guo S, Henry S, Monia B, Geary R, Wang Y. Population pharmacokinetic/pharmacodynamic modelling of eplontersen, an antisense oligonucleotide in development for transthyretin amyloidosis. Br J Clin Pharmacol. 2022 Dec;88(12):5389-5398. doi: 10.1111/bcp.15468. Epub 2022 Aug 7.
Derived from this study: PubMed 33283485Viney NJ, Guo S, Tai LJ, Baker BF, Aghajan M, Jung SW, Yu RZ, Booten S, Murray H, Machemer T, Burel S, Murray S, Buchele G, Tsimikas S, Schneider E, Geary RS, Benson MD, Monia BP. Ligand conjugated antisense oligonucleotide for the treatment of transthyretin amyloidosis: preclinical and phase 1 data. ESC Heart Fail. 2021 Feb;8(1):652-661. doi: 10.1002/ehf2.13154. Epub 2020 Dec 7.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ION-682884 and Vitamin A in people with Healthy Volunteers and hATTR Amyloidosis, run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) (time frame: Up to Day 176). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03728634, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2022.