NCT03814187 (ORION-8) is a Phase 3 clinical trial of Inclisiran Sodium in ASCVD, sponsored by Novartis Pharmaceuticals.

Who is sponsoring NCT03814187?

NCT03814187 is sponsored by Novartis Pharmaceuticals.

What drugs are being tested in NCT03814187?

Interventions in NCT03814187: Inclisiran Sodium.

What condition does NCT03814187 study?

NCT03814187 studies ASCVD, Elevated Cholesterol, Heterozygous Familial Hypercholesterolemia, Homozygous Familial Hypercholesterolemia.

Is NCT03814187 still recruiting?

NCT03814187 is currently completed. Last updated 6 March 2024.

Are results published for NCT03814187?

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

Last reviewed 2024-03-06 · How we verify

NCT03814187: ORION-8

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

Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C

Completed Phase 3 Results posted Last updated 6 March 2024

What this trial tests

Phase 3 trial testing Inclisiran Sodium in ASCVD in 3,275 participants. Completed in 13 February 2023.

Timeline

16 April 2019

Primary endpoint
13 February 2023

13 February 2023

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	3,275
Start date	16 April 2019
Primary completion	13 February 2023
Estimated completion	13 February 2023
Sites	238 locations across Denmark, South Africa, Netherlands, Ukraine, Sweden, United Kingdom, Germany, Hungary

Drugs / interventions tested

Inclisiran Sodium — full drug profile →

Conditions studied

ASCVD — all drugs for ASCVD →
Elevated Cholesterol — all drugs for Elevated Cholesterol →
Heterozygous Familial Hypercholesterolemia — all drugs for Heterozygous Familial Hypercholesterolemia →
Homozygous Familial Hypercholesterolemia — all drugs for Homozygous Familial Hypercholesterolemia →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with ASCVD or Elevated Cholesterol. 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.

Proportion of Subjects Achieving Global Lipid Targets for Their Level of ASCVD Risk Primary · From ORION-8 Day 1 to the end of study (up to 1080 days)

The primary objective of the study is to evaluate the effect of inclisiran treatment on the proportion of subjects achieving prespecified LDL-C targets at end of study (EOS). Target is \<70 mg/dL for atherosclerotic cardiovascular disease (ASCVD) subjects and \<100 mg/dL for ASCVD risk equivalent subjects. Risk equivalent subjects are defined as either type 2 diabetes, familial hypercholesterolemia or a 10-year risk of a cardiovascular event ≥20% as assessed by the Framingham Risk Score or equivalent; without a medical history of coronary heart disease , cerebrovascular disease or peripheral

% of subjects Who Attain Global Lipid Targets at Day 1080 / EOS

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	78.18	75.8 – 80.4
Phase III Placebo-Inclisiran	79.07	76.7 – 81.3
ORION-3 Rollover	76.81	71.4 – 81.6
Total	78.43	76.8 – 80.0

% of ASCVD subjects Who Attain Global Lipid Targets of <70 mg/dL at Day 1080 / EOS

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	79.34	76.8 – 81.7
Phase III Placebo-Inclisiran	79.96	77.4 – 82.4
ORION-3 Rollover	76.70	70.0 – 82.5
Total	79.41	77.7 – 81.1

% of ASCVD Risk Equivalent subjects Who Attain Global Lipid Targets of <100 mg/dL at Day 1080 / EOS

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	72.56	66.1 – 78.3
Phase III Placebo-Inclisiran	74.88	68.6 – 80.5
ORION-3 Rollover	77.00	67.7 – 84.7
Total	74.33	70.4 – 78.0

Incidence of Treatment-emergent Adverse Events (TEAEs) Primary · From ORION-8 Day 1 to the end of study (up to 1080 days)

Safety assessments include adverse events and serious adverse events until the end of study. End of study visit occured at least 90 days following the last inclisiran dose once a decision was made to end the study (either by the subject, investigator or sponsor). For subjects prematurely and permanently discontinued from study treatment, who were not willing to return within the 90 day timeframe, the EOS visit was scheduled as soon as possible, or if decision to discontinue and not return was made at a specific visit, this visit became the EOS visit.

Adverse events

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	1197
Phase III Placebo-Inclisiran	1170
ORION-3 Rollover	181
Total	2548

Adverse events :Treatment-related

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	133
Phase III Placebo-Inclisiran	148
ORION-3 Rollover	16
Total	297

SAEs

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	464
Phase III Placebo-Inclisiran	482
ORION-3 Rollover	43
Total	989

SAEs: Treatment-related

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	2
Phase III Placebo-Inclisiran	2
ORION-3 Rollover	1
Total	5

Fatal SAEs

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	80
Phase III Placebo-Inclisiran	81
ORION-3 Rollover	4
Total	165

Fatal SAEs: Treatment-related

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	0
Phase III Placebo-Inclisiran	0
ORION-3 Rollover	0
Total	0

Absolute Change in LDL-C From the Initial Feeder Study Baseline Secondary · Feeder study baseline, ORION-8 baseline, Day 1080/EOS (ORION-8) (up to a maximum of 2340 days)

Absolute change from baseline in low density lipoprotein cholesterol (LDL-C) was calculated to evaluate the effect of inclisiran on LDL-C levels.

ORION-8 Baseline

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-55.21	-56.9 – -53.5
Phase III Placebo-Inclisiran	0.46	-1.4 – 2.3
ORION-3 Rollover	-61.58	-66.4 – -56.8

Day 1080 / EOS

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-55.81	-58.0 – -53.6
Phase III Placebo-Inclisiran	-54.70	-56.9 – -52.5
ORION-3 Rollover	-64.31	-69.0 – -59.7

Percentage Change in LDL-C From the Initial Feeder Study Baseline Secondary · Feeder study baseline, ORION-8 baseline, Day 1080/EOS (ORION-8) (up to a maximum of 2340 days)

Percentage change from baseline in low density lipoprotein cholesterol (LDL-C) was calculated to evaluate the effect of inclisiran on LDL-C levels.

ORION-8 Baseline

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-50.02	-51.3 – -48.8
Phase III Placebo-Inclisiran	3.10	1.4 – 4.9
ORION-3 Rollover	-48.22	-51.2 – -45.2

Day 1080 / EOS

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-48.96	-50.5 – -47.4
Phase III Placebo-Inclisiran	-49.69	-51.3 – -48.0
ORION-3 Rollover	-49.95	-52.6 – -47.3

Absolute Change From the Initial Feeder Study Baseline in Total Cholesterol, Triglycerides and HDL-C Secondary · Feeder study baseline, ORION-8 baseline, Day 1080/EOS (ORION-8) (up to a maximum of 2340 days)

Absolute change from baseline in total cholesterol, triglycerides and high density lipoprotein cholesterol (HDL-C) was calculated to evaluate the effect of inclisiran on other lipids and lipoproteins.

ORION-8 Baseline Total Cholesterol (TC)

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-59.05	-61.0 – -57.1
Phase III Placebo-Inclisiran	-0.07	-2.2 – 2.1
ORION-3 Rollover	-63.11	-68.3 – -57.9

Day 1080 / EOS Total Cholesterol (TC)

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-58.48	-61.0 – -55.9
Phase III Placebo-Inclisiran	-57.08	-59.6 – -54.6
ORION-3 Rollover	-65.43	-70.5 – -60.3

ORION-8 Baseline Triglycerides

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-21.50	-25.1 – -17.9
Phase III Placebo-Inclisiran	-5.74	-9.5 – -2.0
ORION-3 Rollover	-14.43	-23.7 – -5.1

Day 1080 / EOS Triglycerides

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-19.58	-23.7 – -15.4
Phase III Placebo-Inclisiran	-22.12	-26.3 – -17.9
ORION-3 Rollover	-21.32	-30.3 – -12.4

ORION-8 Baseline HDL Cholesterol

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	3.37	2.9 – 3.9
Phase III Placebo-Inclisiran	0.59	0.1 – 1.1
ORION-3 Rollover	3.41	2.2 – 4.6

Day 1080 / EOS HDL Cholesterol

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	3.60	3.0 – 4.2
Phase III Placebo-Inclisiran	4.39	3.8 – 5.0
ORION-3 Rollover	5.27	3.8 – 6.7

Percentage Change From the Initial Feeder Study Baseline in Total Cholesterol, Triglycerides and HDL-C Secondary · Feeder study baseline, ORION-8 baseline, Day 1080/EOS (ORION-8) (up to a maximum of 2340 days)

Percentage change from baseline in total cholesterol (TC), triglycerides and high density lipoprotein cholesterol (HDL-C) was calculated to evaluate the effect of inclisiran on other lipids and lipoproteins.

ORION-8 Baseline Total Cholesterol (TC)

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-30.64	-31.5 – -29.7
Phase III Placebo-Inclisiran	1.28	0.1 – 2.4
ORION-3 Rollover	-29.49	-31.6 – -27.4

Day 1080 / EOS Total Cholesterol (TC)

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-29.34	-30.5 – -28.2
Phase III Placebo-Inclisiran	-29.53	-30.7 – -28.4
ORION-3 Rollover	-30.44	-32.4 – -28.5

ORION-8 Baseline Triglycerides

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-7.84	-10.0 – -5.7
Phase III Placebo-Inclisiran	3.03	0.8 – 5.2
ORION-3 Rollover	-0.20	-7.6 – 7.2

Day 1080 / EOS Triglycerides

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	-3.90	-6.5 – -1.3
Phase III Placebo-Inclisiran	-6.85	-9.2 – -4.5
ORION-3 Rollover	-3.18	-9.2 – 2.8

ORION-8 Baseline HDL Cholesterol

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	9.28	8.2 – 10.4
Phase III Placebo-Inclisiran	3.48	2.4 – 4.6
ORION-3 Rollover	8.13	5.7 – 10.5

Day 1080 / EOS HDL Cholesterol

Group	Value	95% CI
Phase III Inclisiran-Inclisiran	9.91	8.7 – 11.2
Phase III Placebo-Inclisiran	11.75	10.3 – 13.2
ORION-3 Rollover	12.16	9.3 – 15.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were reported from the start of study in ORION-8 until end of study treatment plus 90 days post treatment, up to a maximum duration of 1080 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase III Inclisiran-Inclisiran

Serious: 464/1512 (31%)

Deaths: 80/1512

Phase III Placebo-Inclisiran

Serious: 482/1478 (33%)

Deaths: 81/1478

ORION-3 Rollover

Serious: 43/284 (15%)

Deaths: 4/284

Total

Serious: 989/3274 (30%)

Deaths: 165/3274

Serious adverse events (559 terms)

Reaction	System	Phase III Inclisiran-Incli…	Phase III Placebo-Inclisiran	ORION-3 Rollover	Total
Coronary artery disease	Cardiac disorders	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
COVID-19 pneumonia	Infections and infestations	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Death	General disorders	—	—	—	—
Angina unstable	Cardiac disorders	—	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—
Ischaemic stroke	Nervous system disorders	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—
Chest pain	General disorders	—	—	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Myocardial ischaemia	Cardiac disorders	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—

Other adverse events (1410 terms — click to expand)

Reaction	System	Phase III Inclisiran-Incli…	Phase III Placebo-Inclisiran	ORION-3 Rollover	Total
COVID-19	Infections and infestations	—	—	—	—
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Diabetes mellitus	Metabolism and nutrition disorders	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Injection site reaction	General disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
Type 2 diabetes mellitus	Metabolism and nutrition disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Cataract	Eye disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—
Lower respiratory tract infection	Infections and infestations	—	—	—	—
Renal impairment	Renal and urinary disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Benign prostatic hyperplasia	Reproductive system and breast disorders	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—
Chronic kidney disease	Renal and urinary disorders	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—	—

Most-reported serious reactions: Coronary artery disease, COVID-19, Acute myocardial infarction, Angina pectoris, Osteoarthritis, Atrial fibrillation, COVID-19 pneumonia, Pneumonia.

Data from ClinicalTrials.gov NCT03814187 adverse events section.

Sponsor's own description

The purpose of this extension study was to evaluate the efficacy, safety, and tolerability of long-term dosing of Inclisiran. The study was a global multicenter study.

Publications & conference data

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

Therapeutic siRNA: state of the art.
Hu B, Zhong L, Weng Y, Peng L, et al · · 2020 · cited 991× · PMID 32561705 · DOI 10.1038/s41392-020-0207-x
The growth of siRNA-based therapeutics: Updated clinical studies.
Zhang MM, Bahal R, Rasmussen TP, Manautou JE, et al · · 2021 · cited 366× · PMID 33513339 · DOI 10.1016/j.bcp.2021.114432
Inclisiran: First Approval.
Lamb YN. · · 2021 · cited 257× · PMID 33620677 · DOI 10.1007/s40265-021-01473-6
Therapeutic siRNA: State-of-the-Art and Future Perspectives.
Friedrich M, Aigner A. · · 2022 · cited 256× · PMID 35997897 · DOI 10.1007/s40259-022-00549-3
RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.
Traber GM, Yu AM. · · 2023 · cited 184× · PMID 35680378 · DOI 10.1124/jpet.122.001234
Paving the Road for RNA Therapeutics.
Dammes N, Peer D. · · 2020 · cited 159× · PMID 32893005 · DOI 10.1016/j.tips.2020.08.004
The landscape of nanoparticle-based siRNA delivery and therapeutic development.
Moazzam M, Zhang M, Hussain A, Yu X, et al · · 2024 · cited 116× · PMID 38204162 · DOI 10.1016/j.ymthe.2024.01.005
Opportunities and challenges for antisense oligonucleotide therapies.
Kuijper EC, Bergsma AJ, Pijnappel WWMP, Aartsma-Rus A. · · 2021 · cited 110× · PMID 32391605 · DOI 10.1002/jimd.12251

Verify or expand the search:

Other trials of Inclisiran Sodium

Trials testing the same drug.

NCT05192941 — Study of Efficacy, Safety, Tolerability and Quality of Life of Inclisiran (KJX839) vs Placebo, on Top of Ongoing Individ · Phase 4 · completed
NCT03399370 — Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol · Phase 3 · completed
NCT03400800 — Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol · Phase 3 · completed

Other recruiting trials for ASCVD

Currently open trials in the same condition.

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Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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NCT07484269 — PULSE Registry: for Patients Receiving Lutetium (177Lu) Vipivotide Tetraxetan · not yet recruiting
NCT07416162 — A Study of Iptacopan in Korean Patients With Paroxysmal Nocturnal Hemoglobinuria or C3 Glomerulopathy · not yet recruiting
NCT07387926 — Safety and Efficacy of Asciminib in Pediatrics and Young Adults With Relapse/Refractory (r/r) Philadelphia Positive (Ph+ · Phase 1, PHASE2 · not yet recruiting

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 NCT03814187 (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 Novartis Pharmaceuticals
Last refreshed: 6 March 2024

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/NCT03814187.

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