Atherosclerotic Cardiovascular DiseasePhase 2ORION-3NCT03060577
An Extension Trial of Inclisiran in Participants With Cardiovascular Disease and High Cholesterol
A Phase 2 study testing Inclisiran and Evolocumab in people with Atherosclerotic Cardiovascular Disease and Symptomatic Atherosclerosis, run by Novartis Pharmaceuticals at 52 sites in 5 countries.
Trial summary
This clinical study was designed to assess the efficacy, safety, and tolerability of long-term dosing of inclisiran and evolocumab given as subcutaneous injections in participants with high cardiovascular risk and elevated low-density lipoprotein cholesterol (LDL-C). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atherosclerotic Cardiovascular Disease, Symptomatic Atherosclerosis, Type2 Diabetes
- What is being tested?
- Inclisiran and Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 382 participants
- Where
- 52 sitesin 5 countries
- Study dates
- 27 Apr 2017to 17 Dec 2021
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Completion of Study MDCO-PCS-15-01 and no contraindication to receiving inclisiran or evolocumab.
- Willing and able to give written and informed consent before initiation of any study related procedures and willing to comply with all required study procedures.
- Willing to self-inject.
Who cannot join
- Any uncontrolled or serious disease, or any medical or surgical condition that may either interfere with participation in the clinical study and/or put the participant at significant risk (according to investigator's [or delegate's] judgment).
- An underlying known disease or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate), might interfere with interpretation of the clinical study results.
- Serious comorbid disease in which the life expectancy of the participant is shorter than the duration of the trial (for example, acute systemic infection, cancer, or other serious illnesses).
- Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver; unexplained alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation greater than 2 times upper limit of normal (ULN); or total bilirubin elevation greater than 1.5 times ULN at study entry visit.
- Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of contraception (for example, oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device) for the entire duration of the study. Exemptions from this criterion are
- Women >2 years postmenopausal (defined as 1 year or longer since their last menstrual period) AND more than 55 years of age
Show all 19Show fewer
- Postmenopausal women (as defined above) and less than 55 years old with a negative pregnancy test within 24 hours of enrollment
- Women who are surgically sterilized at least 3 months prior to enrollment
- Males who are unwilling to use an acceptable method of birth control during the entire study period (that is, condom with spermicide).
- Treatment with investigational medicinal products other than inclisiran or devices within 30 days or five half˗lives, whichever is longer.
- Planned use of investigational medicinal products other than inclisiran or devices during the course of the study.
- Participants with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients
- Previous or current treatment (within 90 days of study entry) with monoclonal antibodies directed towards PCSK9.
- Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:
- Inappropriate for this study, including participants who are unable to communicate or to cooperate with the investigator.
- Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including participants whose cooperation is doubtful due to drug abuse or alcohol dependency).
- Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (for example, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study).
- Involved with, or a relative of, someone directly involved in the conduct of the study.
- Any known cognitive impairment (for example, Alzheimer's Disease).
Trial locations and contacts
52 sites in 5 countries.
52 sites in 5 countries
Netherlands14 sites
Novartis Investigative Site
Amsterdam, 1105 AZ
Novartis Investigative Site
Deventer, 7416 SE
Novartis Investigative Site
Eindhoven, 5611NJ
Novartis Investigative Site
Goes, 4462 RA
Novartis Investigative Site
Hoogeveen, 7909 AA
Novartis Investigative Site
Hoogezand, 9603 AE
Novartis Investigative Site
Hoorn, 1624 NP
Novartis Investigative Site
Leiden, South Holland, 2333 ZA
Novartis Investigative Site
Rotterdam, The Netherlands, 3021 HC
Novartis Investigative Site
The Hague, 2545 CH
Novartis Investigative Site
Utrecht, 3582 KE
Novartis Investigative Site
Utrecht, 3584 CX
Novartis Investigative Site
Venlo, 5912 BL
Novartis Investigative Site
Zwijndrecht, 3331 LZ
United Kingdom14 sites
Novartis Investigative Site
Birmingham, B15 2TH
Novartis Investigative Site
Edinburgh, ED16 4SA
Novartis Investigative Site
Exeter, EX2 5DW
Novartis Investigative Site
Fowey, Cornwall, PL23 1DT
Novartis Investigative Site
High Wycombe, HP16 9QJ
Novartis Investigative Site
Liskeard, Cornwall, PL14 3XA
Novartis Investigative Site
London, NW3 2QG
Novartis Investigative Site
Manchester, M13 9WL
Novartis Investigative Site
Newcastle Upon Tyme, NE4 4LP
Novartis Investigative Site
Penzance, Cornwall, TR18 AJH
Novartis Investigative Site
Plymouth, PL5 3JB
Novartis Investigative Site
St Austell, Cornwall, PL26 7RL
Novartis Investigative Site
Torpoint, Cornwall, PL11 2TB
Novartis Investigative Site
Worcester, WR5 1DD
Canada11 sites
Novartis Investigative Site
Brampton, Ontario, L6Z 4N5
Novartis Investigative Site
Chicoutimi, Quebec, G7H 7K9
Novartis Investigative Site
London, Ontario, N6A 4G5
Novartis Investigative Site
Montreal, Quebec, H2W 1R7
Novartis Investigative Site
Québec, G1V 4G5
Novartis Investigative Site
Québec, G1V 4W2
Novartis Investigative Site
Sherbrooke, Quebec, J1H 5N4
Novartis Investigative Site
St. Johns, A1B 3V6
Novartis Investigative Site
Toronto, Ontario, M5C 2T2
Novartis Investigative Site
Vancouver, British Columbia, V6Z 1Y6
Novartis Investigative Site
Winnipeg, Manitoba, R2H 2A6
United States8 sites
Novartis Investigative Site
Amarillo, Texas, 79106
Novartis Investigative Site
Cincinnati, Ohio, 45229
Novartis Investigative Site
Cincinnati, Ohio, 45246
Novartis Investigative Site
Greenville, Tennessee, 37745
Novartis Investigative Site
Indianapolis, Indiana, 46260
Novartis Investigative Site
Jacksonville, Florida, 32216
Novartis Investigative Site
New York, New York, 10029
Novartis Investigative Site
Richmond, Virginia, 23294
Germany5 sites
Novartis Investigative Site
Berlin, 12203
Novartis Investigative Site
Essen, 45355
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Munich, 80636
About this study
Official title: An Open Label, Active Comparator Extension Trial to Assess the Effect of Long Term Dosing of Inclisiran and Evolocumab Given as Subcutaneous Injections in Participants With High Cardiovascular Risk and Elevated LDL-C (ORION-3)
This clinical study was designed to assess the efficacy, safety, and tolerability of long-term dosing of inclisiran and evolocumab given as subcutaneous injections in participants with high cardiovascular risk and elevated low-density lipoprotein cholesterol (LDL-C).
Read the detailed description
MDCO-PCS-16-01 (ORION-3) was a Phase II, open-label, multicenter, non-randomized, active comparator long term extension study. Total study duration was 4 years from first participant enrolled to the last subject completed. The study consisted of three study periods:
Screening Period: Participants completing study MDCO-PCS-15-01 (ORION-1) were screened for all inclusion and exclusion criteria of study ORION-3.
Treatment Period: Participants fulfilling all eligibility criteria of ORION-3 were enrolled. Participants who received inclisiran in ORION-1 received inclisiran sodium throughout this study up to 4 years (Group 1; Inclisiran-only arm), and participants who received placebo in ORION-1 received evolocumab as open-label comparator up to Day 336, and then transitioned to inclisiran on Day 360 and every 180 days thereafter for up to 4 years (Group 2; Switching arm).
Safety follow up: Participants were followed up for safety during 4 weeks after the last dose of study treatment. Including the Screening Period, the total study duration for a participant was up to 4 years.
- Conditions
- Atherosclerotic Cardiovascular Disease, Symptomatic Atherosclerosis, Type2 Diabetes, Familial Hypercholesterolemia
- Being tested
- Inclisiran, Evolocumab
- Medical subject headings
- Atherosclerosis, Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InclisiranDrug
Also called ALN-PCSSC
Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.
EvolocumabDrug
Also called REPATHA
Evolocumab is a fully human monoclonal antibody that inhibits PCSK9.
| Study group | Role | What they receive |
|---|---|---|
| Inclisiran-only | Experimental | Participants received subcutaneous injections of inclisiran 300 milligrams (mg) on Day 1 and every 180 days thereafter for up to 4 years. Receives: Drug: Inclisiran |
| Switching | Active comparator | Participants received self-administered subcutaneous injections of evolocumab 140 mg on Day 1 and every 14 days thereafter until Day 336. Then, participants received subcutaneous injections of inclisiran 300 mg on Day 360 and every 180 days thereafter for up to 4 years. Receives: Drug: Inclisiran; Drug: Evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change in LDL-C From Baseline of the ORION-1 Study to Day 210 in ORION-3 (Inclisiran Arm)
Percent Change in LDL-C (beta-quantification) from baseline of the ORION-1 Study to Day 210 in ORION-3. A negative percentage score represents a reduction in LDL-C. Change is relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Day 210 (ORION-3) (up to 570 days total)
Secondary outcomes (12)
Percentage Change in LDL-C From Baseline of the ORION-1 Study (Inclisiran Arm)
Percent Change in LDL-C (beta-quantification) from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in LDL-C. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 360, 720, 1080 and 1440 (ORION-3) (up to 390, 720, 1080, 1440 and 1800 days total, respectively)
Absolute Change in LDL-C From Baseline of the ORION-1 Study (Inclisiran Arm)
Absolute Change in LDL-C (beta-quantification) from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in LDL-C. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 360, 720, 1080 and 1440 (ORION-3) (up to 390, 720, 1080, 1440 and 1800 days total, respectively)
Percentage Change in PCSK9 Levels From Baseline of the ORION-1 Study (Inclisiran Arm)
Percent Change in PCSK9 from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in PCSK9. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 360, 720 and 1440 (ORION-3) (up to 390, 720, 1080 and 1800 days total, respectively)
Absolute Change in PCSK9 Levels From Baseline of the ORION-1 Study (Inclisiran Arm)
Absolute Change in PCSK9 from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in PCSK9. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 360, 720 and 1440 (ORION-3) (up to 390, 720, 1080 and 1800 days total, respectively)
Percentage Change in Triglycerides From Baseline of the ORION-1 Study (Inclisiran Arm)
Percent Change in Triglycerides from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in Triglycerides. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Absolute Change in Triglycerides From Baseline of the ORION-1 Study (Inclisiran Arm)
Absolute Change in Triglycerides from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in Triglycerides. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Percentage Change in Apolipoprotein B From Baseline of the ORION-1 Study (Inclisiran Arm)
Percent Change in Apolipoprotein B from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in Apolipoprotein B. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Absolute Change in Apolipoprotein B From Baseline of the ORION-1 Study (Inclisiran Arm)
Absolute Change in Apolipoprotein B from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in Apolipoprotein B. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Percentage Change in Lipoprotein-a From Baseline of the ORION-1 Study (Inclisiran Arm)
Percent Change in Lipoprotein-a from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in Lipoprotein-a. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Absolute Change in Lipoprotein-a From Baseline of the ORION-1 Study (Inclisiran Arm)
Absolute Change in Lipoprotein-a from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in Lipoprotein-a. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Number of Participants With ≥50% LDL-C Reduction From Baseline of the ORION-1 Study (Inclisiran Arm)
Number of Participants with ≥50% LDL-C (beta-quantification) Reduction from baseline of the ORION-1 Study overtime in ORION-3. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
Measured: Baseline (ORION-1) and Days 30, 360, 720 and 1440 (ORION-3) (up to 390, 720, 1080 and 1800 days total, respectively)
Number of Participants Reaching on Treatment LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL (Inclisiran Arm)
Individual responsiveness to inclisiran is defined as the number of Participants Reaching on Treatment LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL at any time point.
Measured: From the start of treatment in ORION-3 to 90 days after end of treatment, assessed up to maximum duration of 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2017
- Study start27 Apr 2017
- Primary completion17 Dec 2021
- Study completion17 Dec 2021
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 Atherosclerotic Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 382 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kausik Ray, MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03060577
- Sponsor's protocol ID
- MDCO-PCS-16-01
- Other IDs
- 2016-003815-37, 2016
- Acronym
- ORION-3
- Status last verified
- Feb 2023
- First submitted
- 17 Feb 2017
- Last updated
- 24 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Ray KK, Troquay RPT, Visseren FLJ, Leiter LA, Scott Wright R, Vikarunnessa S, Talloczy Z, Zang X, Maheux P, Lesogor A, Landmesser U. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. Lancet Diabetes Endocrinol. 2023 Feb;11(2):109-119. doi: 10.1016/S2213-8587(22)00353-9. Epub 2023 Jan 5.
PubMed 36620965Warden BA, Duell PB. Inclisiran: A Novel Agent for Lowering Apolipoprotein B-containing Lipoproteins. J Cardiovasc Pharmacol. 2021 Aug 1;78(2):e157-e174. doi: 10.1097/FJC.0000000000001053.
PubMed 33990512
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Active Comparator Extension Trial to Assess the Effect of Long Term Dosing of Inclisiran and Evolocumab Given as Subcutaneous Injections in Participants With High Cardiovascular Risk and Elevated LDL-C (ORION-3)
- ClinicalTrials.gov ID
- NCT03060577
- Acronym / sponsor ID
- ORION-3 / MDCO-PCS-16-01
- Conditions
- Atherosclerotic Cardiovascular Disease, Symptomatic Atherosclerosis, Type2 Diabetes, Familial Hypercholesterolemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 382 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 27 Apr 2017 (actual)
- Primary completion
- 17 Dec 2021 (actual)
- Study completion
- 17 Dec 2021 (actual)
- First posted
- 23 Feb 2017 (actual)
- Results
- Posted 24 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical study was designed to assess the efficacy, safety, and tolerability of long-term dosing of inclisiran and evolocumab given as subcutaneous injections in participants with high cardiovascular risk and elevated low-density lipoprotein cholesterol (LDL-C).
Detailed description
MDCO-PCS-16-01 (ORION-3) was a Phase II, open-label, multicenter, non-randomized, active comparator long term extension study. Total study duration was 4 years from first participant enrolled to the last subject completed. The study consisted of three study periods:
Screening Period: Participants completing study MDCO-PCS-15-01 (ORION-1) were screened for all inclusion and exclusion criteria of study ORION-3.
Treatment Period: Participants fulfilling all eligibility criteria of ORION-3 were enrolled. Participants who received inclisiran in ORION-1 received inclisiran sodium throughout this study up to 4 years (Group 1; Inclisiran-only arm), and participants who received placebo in ORION-1 received evolocumab as open-label comparator up to Day 336, and then transitioned to inclisiran on Day 360 and every 180 days thereafter for up to 4 years (Group 2; Switching arm).
Safety follow up: Participants were followed up for safety during 4 weeks after the last dose of study treatment. Including the Screening Period, the total study duration for a participant was up to 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inclisiran-only | Experimental | Drug: InclisiranParticipants received subcutaneous injections of inclisiran 300 milligrams (mg) on Day 1 and every 180 days thereafter for up to 4 years. |
| Switching | Active comparator | Drug: Inclisiran, Drug: EvolocumabParticipants received self-administered subcutaneous injections of evolocumab 140 mg on Day 1 and every 14 days thereafter until Day 336. Then, participants received subcutaneous injections of inclisiran 300 mg on Day 360 and every 180 days thereafter for up to 4 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Completion of Study MDCO-PCS-15-01 and no contraindication to receiving inclisiran or evolocumab.
- Willing and able to give written and informed consent before initiation of any study related procedures and willing to comply with all required study procedures.
- Willing to self-inject.
Key exclusion criteria (19 listed)
- Any uncontrolled or serious disease, or any medical or surgical condition that may either interfere with participation in the clinical study and/or put the participant at significant risk (according to investigator's [or delegate's] judgment).
- An underlying known disease or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate), might interfere with interpretation of the clinical study results.
- Serious comorbid disease in which the life expectancy of the participant is shorter than the duration of the trial (for example, acute systemic infection, cancer, or other serious illnesses).
- Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver; unexplained alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation greater than 2 times upper limit of normal (ULN); or total bilirubin elevation greater than 1.5 times ULN at study entry visit.
- Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of contraception (for example, oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device) for the entire duration of the study. Exemptions from this criterion are
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 |
|---|---|---|
| InclisiranAlso: ALN-PCSSCInclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand. | Drug | Inclisiran-only, Switching |
| EvolocumabAlso: REPATHAEvolocumab is a fully human monoclonal antibody that inhibits PCSK9. | Drug | Switching |
Primary outcome
Percentage Change in LDL-C From Baseline of the ORION-1 Study to Day 210 in ORION-3 (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Day 210 (ORION-3) (up to 570 days total)
Percent Change in LDL-C (beta-quantification) from baseline of the ORION-1 Study to Day 210 in ORION-3. A negative percentage score represents a reduction in LDL-C. Change is relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.
12 secondary outcomes
Percentage Change in LDL-C From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 360, 720, 1080 and 1440 (ORION-3) (up to 390, 720, 1080, 1440 and 1800 days total, respectively)
Absolute Change in LDL-C From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 360, 720, 1080 and 1440 (ORION-3) (up to 390, 720, 1080, 1440 and 1800 days total, respectively)
Percentage Change in PCSK9 Levels From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 360, 720 and 1440 (ORION-3) (up to 390, 720, 1080 and 1800 days total, respectively)
Absolute Change in PCSK9 Levels From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 360, 720 and 1440 (ORION-3) (up to 390, 720, 1080 and 1800 days total, respectively)
Percentage Change in Triglycerides From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Absolute Change in Triglycerides From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Percentage Change in Apolipoprotein B From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Absolute Change in Apolipoprotein B From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Percentage Change in Lipoprotein-a From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Absolute Change in Lipoprotein-a From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)
Number of Participants With ≥50% LDL-C Reduction From Baseline of the ORION-1 Study (Inclisiran Arm)
Time frame: Baseline (ORION-1) and Days 30, 360, 720 and 1440 (ORION-3) (up to 390, 720, 1080 and 1800 days total, respectively)
Number of Participants Reaching on Treatment LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL (Inclisiran Arm)
Time frame: From the start of treatment in ORION-3 to 90 days after end of treatment, assessed up to maximum duration of 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36620965Ray KK, Troquay RPT, Visseren FLJ, Leiter LA, Scott Wright R, Vikarunnessa S, Talloczy Z, Zang X, Maheux P, Lesogor A, Landmesser U. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. Lancet Diabetes Endocrinol. 2023 Feb;11(2):109-119. doi: 10.1016/S2213-8587(22)00353-9. Epub 2023 Jan 5.
- Derived from this study: PubMed 33990512Warden BA, Duell PB. Inclisiran: A Novel Agent for Lowering Apolipoprotein B-containing Lipoproteins. J Cardiovasc Pharmacol. 2021 Aug 1;78(2):e157-e174. doi: 10.1097/FJC.0000000000001053.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
Kausik Ray, MD principal investigator
Imperial College London
52 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Inclisiran and Evolocumab in people with Atherosclerotic Cardiovascular Disease and Symptomatic Atherosclerosis, run by Novartis Pharmaceuticals at 52 sites in 5 countries.
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 3 inclusion and 19 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 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 52 sites in Netherlands, United Kingdom, Canada, United States, Germany. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 24 Mar 2023). 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?
Percentage Change in LDL-C From Baseline of the ORION-1 Study to Day 210 in ORION-3 (Inclisiran Arm) (time frame: Baseline (ORION-1) and Day 210 (ORION-3) (up to 570 days total)). 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 NCT03060577, 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 24 Mar 2023.