This study has been transitioned to CTIS with ID 2024-510735-21-00 check the CTIS register for the current data. Study CKJX839B12302 is a pivotal Phase III study designed to test the hypothesis that treatment with inclisiran sodium 300 mg s.c.…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Demonstrate the superiority of inclisiran compared to placebo in reducing the
risk of 3P-MACE (composite of CV death, non-fatal MI and non-fatal ischemic
stroke) in participants with established ASCVD and a LDL-C >=1.8 mmol/L (70
mg/dL) (Endpoint = Time to the first occurrence of 3P-MACE).
Secondary outcome
- Demonstrate the superiority of inclisiran compared to placebo in reducing the
risk of CV death (Endpoint = Time to occurrence of CV death)
- Demonstrate the superiority of inclisiran compared to placebo in reducing the
risk of 4P-MACE (composite of CV death, non-fatal MI, non-fatal ischemic stroke
and urgent coronary revascularization). (Endpoint = Time to the first
occurrence of 4P-MACE)
- Demonstrate the superiority of inclisiran compared to placebo in reducing the
risk of major limb events (MALE) (Endpoint = time to the first occurence of
MALE (including acute lower limb ischemia, or urgent lower limb
revascularization for ischemia)
- Demonstrate the superiority of inclisiran compared to placebo in reducing the
risk of all-cause death (Endpoint = Time to the occurrence of all-cause death)
- Evaluate the safety and tolerability of inclisiran compared to placebo.
Background summary
Inclisiran (KJX839) is the first and only small interfering RNA (siRNA) therapy
to reduce low-density lipoprotein cholesterol (LDL-C) levels via an RNA
interference (RNAi) mechanism of action and could help improve outcomes for
patients with atherosclerotic cardiovascular disease (ASCVD). One key benefit
of the mechanism of action of inclisiran is that the duration of its effect is
significantly longer than that of currently available lipid-lowering therapy,
including PCSK9-blocking mAbs and statins. Inclisiran is approved by EMA based
on a on a robust clinical development program demonstrating effective and
sustained LDL-C reduction of up to 52% in patients with elevated LDL-C despite
maximally tolerated statin therapy. The relationship between LDL-C levels and
CV risk has been clearly documented with evidence from >200 studies involving
>2 million participants that have shown a dose-dependent log-linear association
between the magnitude of exposure to LDL-C and risk of ASCVD. Moreover,
evidence has consistently linked therapeutic reductions in LDL-C with reduced
risk of CV events. While the strength of this correlation enables regulators to
approve LDL-C lowering therapies, a longer and larger trial is needed to
confirm the effects on CV outcomes.
This study is planned to investigate if treatment with inclisiran 300 mg (every
6 months) vs placebo, in adjunct to well-tolerated high-intensity statin
therapy, reduces major adverse cardiovascular events (MACE) in patients with
established ASCVD.
See pages 14-16 of the protocol.
Study objective
This study has been transitioned to CTIS with ID 2024-510735-21-00 check the CTIS register for the current data.
Study CKJX839B12302 is a pivotal Phase III study designed to test the
hypothesis that treatment with inclisiran sodium 300 mg s.c. administered on
Day 1, Month 3 (Day 90), and every 6 months thereafter taken in addition to
well-tolerated high-intensity statin therapy in participants with established
ASCVD will significantly reduce the risk of 3-Point-Major Adverse
Cardiovascular Events (3P-MACE) defined as a composite of CV death, non-fatal
MI and non-fatal ischemic stroke. This will be compared to placebo in adjunct
to well-tolerated high-intensity statin therapy.
Study CKJX839B12302 is specifically aimed at supporting an indication of
inclisiran for the reduction of CV risk in participants with established ASCVD
who have LDL-C >=1.8 mmol/L (70 mg/dL) mol/L (70 mg/dL) despite being on a
background of well-tolerated dose of a high-intensity statin therapy.
Study design
CKJX839B12302 is a randomized, double-blind, parallel group,
placebo-controlled, multi-center, event-driven study evaluating inclisiran
sodium 300 mg s.c. administered on Day 1, Month 3 (Day 90), and every 6 months
thereafter in participants with established ASCVD as evidenced by history of
MI, history of ischemic stroke or symptomatic PAD, and elevated levels of LDL-C
despite being on a well-tolerated dose of a high-intensity statin therapy.
The study consists of:
• A Statin Optimization Period of approximately 5-7 weeks, applicable only to
participants who are not on the minimum doses of the high-intensity statin
therapies pre-specified in Section 3.1 at the Statin Optimization Screening
Visit,
• A Screening Period of approximately 1-2 weeks for all participants, and
• A double-blind Treatment Period with a minimum of 3 years in approximately
75% of the randomized participants.
The overall trial duration is expected to be approximately 6 years, and the
study will continue until at least 1634 participant have experienced a
CEC-confirmed primary 3P-MACE endpoint, at least 570 cardiovasular deaths have
occurred, and approximately 75% of participants have had at least 3 years of
follow-up time (Figure 1-1).
See protocol pages 18-32.
Intervention
Participants will be randomized in a 1:1 ratio to double-blind s.c. injections
of inclisiran sodium 300 mg or placebo.
Investigational and control drugs will not be dispensed to the participants but
rather administered by qualified healthcare personnel.
Study burden and risks
- Injection site reactions: itching, pain, rash, redness, changes of the color
of the skin, ulcers, swelling, sensitive skin, or other reactions near the
injection site.
- Allergic reactions. Frequently seen allergic reactions are rash, itching,
skin problems, swelling of the face and throat and problems with breathing. So
far no general allergic reactions have been reported with inclisiran and no
symptoms have been seen which matches an
- Blood sampling can cause some pain and/or bruising.
- Fasting could cause dizziness, headache, stomach discomfort, or fainting.
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Listed location countries
Age
Inclusion criteria
1) Male or female >=40 years of age
2) Fasting LDL-C >=1.8 mmol/L (70 mg/dL) at the Screening Visit
3) At the Screening Visit, participants must be on a stable (>=4 weeks) and
well-tolerated lipid-lowering regimen (including e.g. with or without
Ezetimibe) that must include a high-intensity statin therapy with either
atorvastatin >=40 mg QD or rosuvastatin >=20 mg QD
4) Established CV disease, defined as any of the following: Previous myocardial
infarction, Previous ischemic stroke, Symptomatic peripheral arterial disease
(PAD).
Other inclusion criteria are listed in the clinical study protocol.
Exclusion criteria
1) Acute coronary syndrome, ischemic stroke, peripheral arterial
revascularization procedure or amputation due to atherosclerotic disease <4
weeks prior to the first study visit.
2) Planned or expected cardiac, cerebrovascular or peripheral artery surgery or
coronary re-vascularization within the 6 months after the first study visit.
3) New York Heart Association (NYHA) class III or IV heart failure
4) Active liver disease
5) Previous exposure to inclisiran or any other non-mAb PCSK9-targeted therapy,
either as an investigational or marketed drug within 2 years prior to the first
study visit
6) Pregnant or nursing (lactating) women
Other exclusion criteria are listed in the clinical study protocol.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-510735-21-00 |
| EudraCT | EUCTR2021-002006-27-NL |
| ClinicalTrials.gov | NCT05030428 |
| CCMO | NL78939.000.21 |