A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

A Two-Part (Double-Blind Placebo Controlled/Open-Label) Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Subjects With Homozygous Familial Hypercholesterolemia (Hofh) (ORION-5)

ClinicalTrials.gov Identifier: NCT03851705

Novartis Reference Number: MDCO-PCS-17-02

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

This study is a Phase III,A two-part (double-blind placebo-controlled/open-label) multicenter study to evaluate safety, tolerability, and efficacy of inclisiran in subjects with homozygous familial hypercholesterolemia (HoFH).

Condition 
Homozygous Familial Hypercholesterolemia
Phase 
Phase 3
Overall status 
Active, not recruiting
Enrollment count 
56 participants
Start date 
Feb 06, 2019
Completion date 
Sep 01, 2021
Gender 
All
Age(s)
18 Years - 80 Years (Adult, Older Adult)

Interventions

Drug
Inclisiran for injection
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.
Drug
Placebos
Sterile normal saline (0.9% sodium chloride in water for injection)

Eligibility Criteria

Inclusion Criteria:

Diagnosis of HoFH by genetic confirmation or a clinical diagnosis based on a history of an untreated LDL-C concentration >500 mg/dL (13 mmol/L) together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents
Stable on a low-fat diet.
Subjects on statins should be receiving a maximally tolerated dose. Maximum tolerated dose is defined as the maximum dose of statin that can be taken on a regular basis without intolerable adverse events.
Subjects not receiving statins must have documented evidence of intolerance to at least two different statins.
Subjects on lipid-lower therapies (such as 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.
Fasting central laboratory LDL-C concentration ≥130 mg/dL (3.4 mmol/L).
Triglyceride concentration <400 mg/dL (4.5 mmol/L)
No current or planned renal dialysis or renal transplantation
Subjects on a documented regimen of LDL or plasma apheresis will be allowed to continue the apheresis during the study, if needed.
Subjects must be willing and able to give written informed consent before initiation of any study-related procedures. The subject should be willing to comply with all required study procedures.
Willing to follow all study procedures including adherence to dietary guidelines, study visits, fasting blood draws, and compliance with study treatment regimens.

Exclusion Criteria:

Use of Mipomersen or Lomitapide therapy within 5 months of screening
Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
New York Heart Association (NYHA) class IV heart failure or last known left ventricular ejection fraction <25%
Major adverse cardiovascular event within 3 months prior to randomization
Planned cardiac surgery or revascularization
Uncontrolled severe hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite anti-hypertensive therapy
Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST), elevation >3x ULN, or total bilirubin >2x upper limit of normal (ULN) at screening confirmed by a repeat measurement at least 1 week apart
Severe concomitant noncardiovascular disease that carries the risk of reducing life expectancy to less than the duration of the trial
History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or commencement of systemic therapy as treatment during the 3 years prior to randomization

Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least one acceptable effective method of contraception (eg, oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, intrauterine device) for the entire duration of the study. Exemptions from this criterion:

Women >2 years postmenopausal (defined as 1 year or longer since their 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 enrolment
Women who are surgically sterilized at least 3 months prior to enrolment
Known history of alcohol and/or drug abuse within 5 years

Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:

Subjects 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 subjects whose cooperation is doubtful due to drug abuse or alcohol dependency)
Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study)
Have any medical or surgical condition, which in the opinion of the investigator would put the subject at increased risk from participating in the study
Persons directly involved in the conduct of the study
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 subject at significant risk (according to investigator's [or delegate] judgment) if he/she participates in the clinical study
Any underlying known disease, or surgical, physical, or medical condition that, in the opinion of the Investigator, might interfere with the interpretation of clinical study results
Treatment with other investigational medicinal products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer
Previous participation in the study
Hypersensitivity to any of the ingredients of Inclisiran

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Locations

Hong Kong
(50852-001) Queen Mary Hospital
-
Hong Kong,
-
Hong Kong
Israel
(50972-001) Hadassah Hospital Lipid Research Ein Kerem
-
Jerusalem, 91120
-
Israel
Russian Federation
(50007-001) Research Institute of Complex Issues of Cardiovascular Diseases
-
Kemerovo, 650002
-
Russian Federation
(50007-003) National Medical Research Centre of Cardiology
-
Moscow, 121552
-
Russian Federation
(50007-002) Hospital for War Veterans
-
Saint Petersburg, 193079
-
Russian Federation
Serbia
(50381-001) Clinical Center of Serbia
-
Belgrad, 11000
-
Serbia
South Africa
(50027-001) Johannesburg Hospital
-
Johannesburg, 2193
-
South Africa
Taiwan
(50886-001) Taipei Veterans General Hospital
-
Taipei, 11217
-
Taiwan
Turkey
(50090-002) University of Health Sciences
-
Etlik, 06010
-
Turkey
(50090-003) Istanbul University
-
Istanbul, 34093
-
Turkey
(50090-001) Ege Universitesi
-
İzmir, 35040
-
Turkey
Ukraine
(50380-002) IMunicipal Non-commercial Enterprise "Ivano-Frankivsk Regional Clinical Cardiology Center Ivano-Frankivsk Regional Council"
-
Ivano-Frankivs'k, 76018
-
Ukraine
(50380-001) National Scientific Center
-
Kyiv, 03680
-
Ukraine

Have a question?

Call 1-999-669-6682 or email [email protected]