NCT03728634 is a Phase 1, PHASE2 clinical trial of ION-682884 in Healthy Volunteers, sponsored by Ionis Pharmaceuticals, Inc..

Who is sponsoring NCT03728634?

NCT03728634 is sponsored by Ionis Pharmaceuticals, Inc..

What drugs are being tested in NCT03728634?

Interventions in NCT03728634: ION-682884, Placebo, Vitamin A.

What condition does NCT03728634 study?

NCT03728634 studies Healthy Volunteers, hATTR Amyloidosis.

Is NCT03728634 still recruiting?

NCT03728634 is currently completed. Last updated 19 December 2022.

Are results published for NCT03728634?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2022-12-19 · How we verify

NCT03728634

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

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 ).

Completed Phase 1, PHASE2 Results posted Last updated 19 December 2022

What this trial tests

Phase 1, PHASE2 trial testing ION-682884 in Healthy Volunteers in 47 participants. Completed in 20 February 2020.

Timeline

21 December 2018

Primary endpoint
20 February 2020

20 February 2020

Quick facts

Lead sponsor	Ionis Pharmaceuticals, Inc.
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	47
Start date	21 December 2018
Primary completion	20 February 2020
Estimated completion	20 February 2020
Sites	1 location across Canada

Drugs / interventions tested

ION-682884
Placebo
Vitamin A — full drug profile →

Conditions studied

Healthy Volunteers — all drugs for Healthy Volunteers →
hATTR Amyloidosis — all drugs for hATTR Amyloidosis →

Sponsor

Ionis Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 18 to 65, any sex, with Healthy Volunteers or hATTR Amyloidosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Multiple Dose Cohort: Placebo	3
Multiple Dose Cohort A: ION-682884 45 mg	1
Multiple Dose Cohort E: ION-682884 60 mg	3
Multiple Dose Cohort B: ION-682884 90 mg	7
Single Dose Cohort: Placebo	1
Single Dose Cohort C: ION-682884 120 mg	4

Percentage of Participants Using Concomitant Medications Primary · 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.

Group	Value	95% CI
Multiple Dose Cohort: Placebo	0.0
Multiple Dose Cohort A: ION-682884 45 mg	0.0
Multiple Dose Cohort E: ION-682884 60 mg	30.0
Multiple Dose Cohort B: ION-682884 90 mg	0.0
Single Dose Cohort: Placebo	0.0
Single Dose Cohort C: ION-682884 120 mg	22.2

Number of Participants With Clinically Significant Laboratory Values Primary · 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.

Group	Value	95% CI
Multiple Dose Cohort: Placebo	0
Multiple Dose Cohort A: ION-682884 45 mg	0
Multiple Dose Cohort E: ION-682884 60 mg	0
Multiple Dose Cohort B: ION-682884 90 mg	0
Single Dose Cohort: Placebo	0
Single Dose Cohort C: ION-682884 120 mg	0

Number of Participants With Clinically Significant Physical Examination Findings Primary · 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.

Group	Value	95% CI
Multiple Dose Cohort: Placebo	0
Multiple Dose Cohort A: ION-682884 45 mg	0
Multiple Dose Cohort E: ION-682884 60 mg	0
Multiple Dose Cohort B: ION-682884 90 mg	0
Single Dose Cohort: Placebo	0
Single Dose Cohort C: ION-682884 120 mg	0

Number of Participants With Clinically Significant Electrocardiogram (ECG) Values Primary · 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.

Group	Value	95% CI
Multiple Dose Cohort: Placebo	0
Multiple Dose Cohort A: ION-682884 45 mg	0
Multiple Dose Cohort E: ION-682884 60 mg	0
Multiple Dose Cohort B: ION-682884 90 mg	0
Single Dose Cohort: Placebo	0
Single Dose Cohort C: ION-682884 120 mg	0

Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx Secondary · Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85

Day 1

Group	Value	95% CI
Multiple Dose Cohort A: ION-682884 45 mg	0.143	± 39.3
Multiple Dose Cohort E: ION-682884 60 mg	0.239	± 62.6
Multiple Dose Cohort B: ION-682884 90 mg	0.332	± 43.6
Single Dose Cohort C: ION-682884 120 mg	0.542	± 65.0

Day 85

Group	Value	95% CI
Multiple Dose Cohort A: ION-682884 45 mg	0.215	± 66.1
Multiple Dose Cohort E: ION-682884 60 mg	0.282	± 74.5
Multiple Dose Cohort B: ION-682884 90 mg	0.471	± 69.5

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx Secondary · Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85

Day 1

Group	Value	95% CI
Multiple Dose Cohort A: ION-682884 45 mg	2.01	1.00 – 4.00
Multiple Dose Cohort E: ION-682884 60 mg	6.00	3.00 – 12.0
Multiple Dose Cohort B: ION-682884 90 mg	2.25	1.00 – 6.00
Single Dose Cohort C: ION-682884 120 mg	4.00	1.00 – 8.00

Day 85

Group	Value	95% CI
Multiple Dose Cohort A: ION-682884 45 mg	3.00	1.00 – 3.00
Multiple Dose Cohort E: ION-682884 60 mg	1.00	1.00 – 3.00
Multiple Dose Cohort B: ION-682884 90 mg	3.00	1.00 – 8.00

AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx Secondary · 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

Day 1

Group	Value	95% CI
Single Dose Cohort C: ION-682884 120 mg	6.78	± 20.3

Day 85

Group	Value	95% CI
Multiple Dose Cohort A: ION-682884 45 mg	1.81	± 36.3
Multiple Dose Cohort E: ION-682884 60 mg	2.73	± 43.2
Multiple Dose Cohort B: ION-682884 90 mg	4.35	± 43.2

CL/F: Apparent Total Clearance of ION-TTR-LRx Secondary · 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

Day 1

Group	Value	95% CI
Single Dose Cohort C: ION-682884 120 mg	17.7	± 20.3

Day 85

Group	Value	95% CI
Multiple Dose Cohort A: ION-682884 45 mg	24.8	± 36.3
Multiple Dose Cohort E: ION-682884 60 mg	22.0	± 43.2
Multiple Dose Cohort B: ION-682884 90 mg	20.7	± 43.2

t1/2λz: Termination Half-Life of ION-TTR-LRx Secondary · Up to 92 hours; post-dose on Day 85 for Cohorts A, B, and E, and on Day 1 for Cohort C

Day 1

Group	Value	95% CI
Single Dose Cohort C: ION-682884 120 mg	17.9	12.8 – 40.7

Day 85

Group	Value	95% CI
Multiple Dose Cohort A: ION-682884 45 mg	22.3	10.3 – 52.7
Multiple Dose Cohort E: ION-682884 60 mg	30.3	20.1 – 58.9
Multiple Dose Cohort B: ION-682884 90 mg	24.8	15.2 – 45.0

Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period Secondary · From 0 to 24 hours post-dose on Days 1 and 85

Day 1

Group	Value	95% CI
Multiple Dose Cohort A: ION-682884 45 mg	17.0	± 54.1
Multiple Dose Cohort E: ION-682884 60 mg	23.5	± 62.3
Multiple Dose Cohort B: ION-682884 90 mg	29.9	± 146
Single Dose Cohort C: ION-682884 120 mg	87.4	± 87.9

Day 85

Group	Value	95% CI
Multiple Dose Cohort A: ION-682884 45 mg	40.6	± 38.0
Multiple Dose Cohort E: ION-682884 60 mg	68.3	± 57.2
Multiple Dose Cohort B: ION-682884 90 mg	133	± 33.8

Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx Secondary · Baseline, Days 29 and 99

Day 29

Group	Value	95% CI
Multiple Dose Cohort: Placebo	-0.225	± 2.935
Multiple Dose Cohort A: ION-682884 45 mg	-13.40	± 4.312
Multiple Dose Cohort E: ION-682884 60 mg	-18.63	± 4.933
Multiple Dose Cohort B: ION-682884 90 mg	-19.42	± 5.441
Single Dose Cohort: Placebo	0.725	± 1.732
Single Dose Cohort C: ION-682884 120 mg	-20.06	± 3.615

Day 99

Group	Value	95% CI
Multiple Dose Cohort: Placebo	0.908	± 4.050
Multiple Dose Cohort A: ION-682884 45 mg	-18.60	± 2.911
Multiple Dose Cohort E: ION-682884 60 mg	-22.02	± 3.564
Multiple Dose Cohort B: ION-682884 90 mg	-21.91	± 5.175

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 176. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Multiple Dose Cohort: Placebo

Serious: 0/6 (0%)

Deaths: 0/6

Multiple Dose Cohort A: ION-682884 45 mg

Serious: 0/10 (0%)

Deaths: 0/10

Multiple Dose Cohort E: ION-682884 60 mg

Serious: 0/10 (0%)

Deaths: 0/10

Multiple Dose Cohort B: ION-682884 90 mg

Serious: 0/10 (0%)

Deaths: 0/10

Single Dose Cohort: Placebo

Serious: 0/2 (0%)

Deaths: 0/2

Single Dose Cohort C: ION-682884 120 mg

Serious: 0/9 (0%)

Deaths: 0/9

Other adverse events (20 terms — click to expand)

Reaction	System	Multiple Dose Cohort: Plac…	Multiple Dose Cohort A: IO…	Multiple Dose Cohort E: IO…	Multiple Dose Cohort B: IO…	Single Dose Cohort: Placebo	Single Dose Cohort C: ION-…
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Weight increased	Investigations	—	—	—	—	—	—
Injection site bruising	General disorders	—	—	—	—	—	—
Injection site erythema	General disorders	—	—	—	—	—	—
Injection site reaction	General disorders	—	—	—	—	—	—
Injection site swelling	General disorders	—	—	—	—	—	—
Vessel puncture site bruise	General disorders	—	—	—	—	—	—
Vessel puncture site paraesthesia	General disorders	—	—	—	—	—	—
Skin abrasion	Injury, poisoning and procedural complications	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Influenza like illness	General disorders	—	—	—	—	—	—
Malaise	General disorders	—	—	—	—	—	—
Limb discomfort	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—

Data from ClinicalTrials.gov NCT03728634 adverse events section.

Sponsor's own description

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 ).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Noncoding RNA therapeutics - challenges and potential solutions.
Winkle M, El-Daly SM, Fabbri M, Calin GA. · · 2021 · cited 1123× · PMID 34145432 · DOI 10.1038/s41573-021-00219-z
Antisense technology: A review.
Crooke ST, Liang XH, Baker BF, Crooke RM. · · 2021 · cited 237× · PMID 33600796 · DOI 10.1016/j.jbc.2021.100416
Pathophysiology and Therapeutic Approaches to Cardiac Amyloidosis.
Griffin JM, Rosenblum H, Maurer MS. · · 2021 · cited 130× · PMID 33983835 · DOI 10.1161/circresaha.121.318187
ATTR Amyloidosis: Current and Emerging Management Strategies: <i>JACC: CardioOncology</i> State-of-the-Art Review.
Griffin JM, Rosenthal JL, Grodin JL, Maurer MS, et al · · 2021 · cited 110× · PMID 34729521 · DOI 10.1016/j.jaccao.2021.06.006
Diagnosis and Treatment of Hereditary Transthyretin Amyloidosis (hATTR) Polyneuropathy: Current Perspectives on Improving Patient Care.
Luigetti M, Romano A, Di Paolantonio A, Bisogni G, et al · · 2020 · cited 91× · PMID 32110029 · DOI 10.2147/tcrm.s219979
Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis.
Carroll A, Dyck PJ, de Carvalho M, Kennerson M, et al · · 2022 · cited 79× · PMID 35256455 · DOI 10.1136/jnnp-2021-327909
Hereditary transthyretin amyloidosis overview.
Manganelli F, Fabrizi GM, Luigetti M, Mandich P, et al · · 2022 · cited 78× · PMID 33188616 · DOI 10.1007/s10072-020-04889-2
Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review.
Nappi F. · · 2024 · cited 72× · PMID 38612441 · DOI 10.3390/ijms25073630

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Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT03728634 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Ionis Pharmaceuticals, Inc.
Last refreshed: 19 December 2022

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03728634.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing

NCT03728634

Quick facts

Drugs / interventions tested

Conditions studied

Sponsor

Who can join

Results — posted to ClinicalTrials.gov

Adverse events — posted to ClinicalTrials.gov

Sponsor's own description

Publications & conference data

Related trials

Other recruiting trials for Healthy Volunteers

Other Ionis Pharmaceuticals, Inc. trials

Verify against primary sources