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Heterozygous Familial HypercholesterolemiaPhase 3ORION-9NCT03397121

Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH)

A Phase 3 study testing Inclisiran in people with Heterozygous Familial Hypercholesterolemia and Elevated Cholesterol, run by The Medicines Company at 45 sites in 8 countries.

Completed

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

Official record
Search all trials

Trial summary

This is a Phase III, placebo-controlled, double-blind, randomized study in participants with HeFH and elevated LDL-C to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) injection(s) of inclisiran. The study will be multicenter and international. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Inclisiran
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
482 participants
Where
45 sitesin 8 countries
Study dates
28 Nov 2017to 17 Sep 2019
Phase
Phase 3
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

  • Participants may be included if they meet all of the following inclusion criteria prior to randomization:
  • Male or female participants ≥18 years of age.
  • History of HeFH with a diagnosis of HeFH by genetic testing; and/or a documented history of untreated LDL-C of >190 mg/dL, and a family history of familial hypercholesterolemia, elevated cholesterol or early heart disease that may indicate familial hypercholesterolemia.
  • Serum LDL-C ≥2.6 millimoles (mmol)/liter (L) (≥100 mg/dL) at screening.
  • Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
  • Participants on statins should be receiving a maximally tolerated dose.
  • Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
  • Participants on lipid-lowering therapies (such as a statin and/or ezetimibe) should be on a stable dose for ≥30 days before screening with no planned medication or dose change during study participation.

Who cannot join

  • Participants will be excluded from the study if any of the following exclusion criteria apply immediately prior to randomization:
  • New York Heart Association (NYHA) class IV heart failure.
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled severe hypertension
  • Active liver disease
  • Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of highly effective contraception (failure rate less than 1% per year) (combined oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, or intrauterine device) for the entire duration of the study. Exemptions from this criterion:
Show all 13Show fewer
  • Women >2 years postmenopausal (defined as 1 year or longer since last menstrual period) AND more than 55 years of age.
  • Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization.
  • 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 (condom with spermicide).
  • Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.
  • Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9.
  • The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial locations and contacts

45 sites in 8 countries.

45 sites in 8 countries

United States10 sites

  • Site 90001-047

    Boca Raton, Florida, 33434

  • Site 90001-004

    Boston, Massachusetts, 02114

  • Site 90001-012

    Butte, Montana, 59701

  • Site 90001-002

    Cincinnati, Ohio, 45227

  • Site 90001-112

    Las Vegas, Nevada, 89119

  • Site 90001-005

    Mission Viejo, California, 92691

  • Site 90001-001

    Newport Beach, California, 92663

  • Site 90001-056

    Saint Paul, Minnesota, 55102

  • Site 90001-015

    Stanford, California, 94305

  • Site 90001-014

    Summit, New Jersey, 07901

Other trials in United States

South Africa9 sites

  • Site 90027-003

    Bloemfontein, 9301

  • Site 90027-004

    Cape Town, Western Cape, 7130

  • Site 90027-005

    Cape Town, 7130

  • Site 90027-001

    Cape Town, 7500

  • Site 90027-008

    Cape Town, 7530

  • Site 90027-010

    Johannesburg, 2193

  • Site 90027-007

    Pretoria, 0157

  • Site 90027-006

    Pretoria, 0184

  • Site 90027-009

    Witbank, 1035

Other trials in South Africa

Denmark6 sites

  • Site 90045-001

    Aalborg, DK-9000

  • Site 90045-004

    Esbjerg, DK-6700

  • Site 90045-003

    Herning, 7400

  • Site 90045-006

    Hvidovre, 2650

  • Site 90045-002

    Roskilde, DK-4000

  • Site 90045-005

    Viborg, DK-8800

Other trials in Denmark

Spain6 sites

  • Site 90034-003

    A Coruña, 15006

  • Site 90034-005

    Barcelona

  • Site 90034-004

    Córdoba, 14004

  • Site 90034-006

    L'Hospitalet de Llobregat, 8907

  • Site 90034-001

    Reus, 43204

  • Site 90034-002

    Zaragoza, 50009

Other trials in Spain

Netherlands5 sites

  • Site 90031-001

    Amersfoort, 3813 TZ

  • Site 90031-003

    Amsterdam, 1105 AZ

  • Site 90031-009

    Hoorn, 1624 NP

  • Site 90031-006

    Tilburg, 5042 AD

  • Site 90031-005

    Utrecht, 3584 CX

Other trials in Netherlands

Canada3 sites

  • Site 90011-005

    Chicoutimi, Quebec, G7H 7K9

  • Site 90011-001

    Montreal, Quebec, H2W 1R7

  • Site 90011-002

    Québec, Quebec, G1V 4W2

Other trials in Canada

Czechia3 sites

  • Site 90420-001

    Prague, 140 21

  • Site 90420-006

    Prague, 180 00

  • Site 90420-005

    Trutnov, 541 01

Other trials in Czechia

Sweden3 sites

  • Site 90046-002

    Gothenburg, SE-41345

  • Site 90046-001

    Stockholm, SE-11157

  • Site 90046-003

    Stockholm, SE-14186

Other trials in Sweden

About this study

Official title: Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH) and Elevated Low-Density Lipoprotein Cholesterol (LDL-C).

This is a Phase III, placebo-controlled, double-blind, randomized study in participants with HeFH and elevated LDL-C to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) injection(s) of inclisiran. The study will be multicenter and international.

Being tested
Inclisiran, Placebo
Keywords
HeFH, LDL-C, Inclisiran
Medical subject headings
Hypercholesterolemia

What participants receive

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

  • InclisiranDrug

    Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.

  • PlaceboDrug

    Also called Saline Solution

    Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Study groups in NCT03397121
Study groupRoleWhat they receive
InclisiranExperimentalInclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90 then every 6 months.
Receives: Drug: Inclisiran
PlaceboPlacebo comparatorPlacebo will be administered as SC injections of saline solution on Day 1, Day 90 then every 6 months.
Receives: Drug: Placebo

What is being measured

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

  1. Percent Change in LDL-C From Baseline To Day 510

    Measured: Baseline, Day 510

  2. Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 540

    Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 90 reported

    Measured: Baseline, Day 90

Secondary outcomes (6)

  1. Absolute Change in LDL-C From Baseline to Day 510

    Measured: Baseline, Day 510

  2. Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540

    Assessments performed at Baseline, Day 90, Day 540, absolute change at Day 90 reported

    Measured: Baseline, Day 90

  3. Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510

    Measured: Baseline, Day 510

  4. Percentage Change in Total Cholesterol From Baseline to Day 510

    Measured: Baseline, Day 510

  5. Percent Change in Apolipoprotein B (Apo-B) From Baseline To Day 510

    Measured: Baseline, Day 510

  6. Percent Change in Non-high-density Lipoprotein (HDL)-C From Baseline To Day 510

    Measured: Baseline, Day 510

Timeline

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

  1. First posted11 Jan 2018
  2. Study start28 Nov 2017
  3. Primary completion27 Aug 2019
  4. Study completion17 Sep 2019

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
482 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03397121
Sponsor's protocol ID
MDCO-PCS-17-03
Other IDs
2017-002472-30, 2017
Acronym
ORION-9
Status last verified
Oct 2020
First submitted
2 Jan 2018
Last updated
28 Oct 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Landmesser U, Ray KK, Raal FJ, Garcia Conde L, Han J, Koenig W, Leiter LA, Schwartz GG, Wright RS; on behalf of the ORION Investigators. Inclisiran in Patients with CKD: Post Hoc Pooled Analysis of Three Phase 3 Trials. J Am Soc Nephrol. 2026 Jul 1;37(7):1497-1506. doi: 10.1681/ASN.0000001006. Epub 2026 Jan 28.

    PubMed 41604274

  • Leiter LA, Raal FJ, Schwartz GG, Koenig W, Ray KK, Landmesser U, Han J, Conde LG, Wright RS. Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the ORION-9, ORION-10 and ORION-11 Phase 3 randomized trials. Diabetes Obes Metab. 2024 Aug;26(8):3223-3237. doi: 10.1111/dom.15650. Epub 2024 May 17.

    PubMed 38757725

  • Dutta S, Shah R, Singhal S, Singh S, Piparva K, Katoch CDS. A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients. Expert Opin Drug Saf. 2024 Feb;23(2):187-198. doi: 10.1080/14740338.2023.2293201. Epub 2023 Dec 19.

    PubMed 38063346

  • Raal FJ, Kallend D, Ray KK, Turner T, Koenig W, Wright RS, Wijngaard PLJ, Curcio D, Jaros MJ, Leiter LA, Kastelein JJP; ORION-9 Investigators. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Apr 16;382(16):1520-1530. doi: 10.1056/NEJMoa1913805. Epub 2020 Mar 18.

    PubMed 32197277

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Inclisiran in people with Heterozygous Familial Hypercholesterolemia and Elevated Cholesterol, run by The Medicines Company at 45 sites in 8 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 8 inclusion and 13 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 28 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States, South Africa, Denmark, Spain, Netherlands and 3 more countries. 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 phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 28 Oct 2020). 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?

Percent Change in LDL-C From Baseline To Day 510 (time frame: Baseline, Day 510). The study lists 2 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 NCT03397121, which also lists 4 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 28 Oct 2020.

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