An open-label, single arm, multicenter extension study to evaluate long-term safety and tolerability of inclisiran in participants with heterozygous or homozygous familial hypercholesterolemia who have completed the adolescent ORION-16 or ORION-13 studies (VICTORION-PEDS-OLE)

As the degree and duration of exposure to elevated LDL-C levels increases the
atherosclerotic burden, early treatment of FH to lower LDL-C levels is vital.
HeFH, guidelines recommend statins as first line drug therapy for
lipid-lowering in children, however, multiple drug therapy is often needed. In
the more severe homozygous FH, maximal statin therapy is the mainstay drug
treatment, often in combination with ezetimibe and other lipid-modifying
therapy. However, even at the highest doses of the most efficacious statins,
only modest reductions in LDL-C plasma levels of 10-25% are observed in most
patients. Where available, low-density lipoprotein (LDL)-apheresis is regarded
an important adjunctive treatment.
Inclisiran is a double-stranded small interfering RNA which inhibits
translation of PCSK9 protein in hepatocytes. Reduced intrahepatic PCSK9
increases LDLR recycling and expression on the hepatocyte cell surface, thereby
increasing LDL-C uptake and lowering LDL-C levels in the circulation.
Two currently ongoing randomized, multicenter, double-blind, Phase 3 studies
(ORION-16 and ORION-13) evaluate the effects of inclisiran sodium 300mg s.c. on
lowering LDL-C levels in adolescents with HeFH or HoFH. To collect long-term
safety, tolerability and efficacy data and to ensure continuous treatment of
participants with HeFH or HoFH upon completion of the Phase 3 studies with
inclisiran, participants who complete ORION-16 or ORION-13 will be offered the
opportunity to enroll in the present VICTORION-PEDS-OLE study (CKJX839C12001B)
and thus continue to receive open-label treatment with 300mg s.c. inclisiran
sodium. Only participants who derived a treatment benefit from inclisiran in
ORION-16 and -13, per the investigator's opinion, will be included in this
study.

This study has been transitioned to CTIS with ID 2023-507278-41-00 check the CTIS register for the current data.

The primary objective of the study is to evaluate the long-term safety and
tolerability of inclisiran in participants with HeFH or HoFH

This study is an open-label, single arm, multicenter, extension study to
characterize long-term safety and tolerability of inclisiran and to provide
access to participants with HeFH or HoFH who have completed the adolescent
CKJX839C12301 (ORION-16) or CKJX839C12302 (ORION-13) studies with inclisiran
and are judged by the respective study investigator to derive benefit from
inclisiran treatment. Long-term efficacy of inclisiran will also be assessed.

All participants will receive open-label, subcutaneous (s.c.) injections of
inclisiran sodium 300mg.

Injections site reactions: itching, pain, rash, redness, skin color changes,
sores, swelling, tenderness, or other reactions around the injection site.
Allergic reactions: these reactions can be mild or serious. common symptoms of
an allergic reaction include rash, itching, skin problems, swelling of the face
and throat, or trouble breathing. No general allergic reactions or signs or
symptoms suggestive of general allergic reactions have been seen following
administration of inclisiran in three large previous clinical studies.
Blood sampling can cause some pain and/or bruising.