Inclisiran Sodium for Hypercholesterolemia

Phase-Based Estimates
2
Effectiveness
3
Safety
Research Site 10001-027, Pembroke Pines, FL
Hypercholesterolemia+5 More
Inclisiran Sodium - Drug
Eligibility
18+
All Sexes
Eligible conditions
Hypercholesterolemia

Study Summary

This study is evaluating whether long-term dosing of Inclisiran is safe and effective.

See full description

Eligible Conditions

  • Hypercholesterolemia
  • Hyperlipoproteinemia Type II
  • Homozygous Familial Hypercholesterolaemia (HoFH)
  • Heterozygous Familial Hypercholesterolemia (HeFH)
  • ASCVD
  • elevations of serum cholesterol

Treatment Effectiveness

Effectiveness Estimate

2 of 3
This is better than 85% of similar trials

Study Objectives

This trial is evaluating whether Inclisiran Sodium will improve 5 primary outcomes, 6 secondary outcomes, and 1 other outcome in patients with Hypercholesterolemia. Measurement will happen over the course of Baseline, Day 1080.

Baseline, Day 1080
Absolute and percentage change in LDL-C from baseline
Absolute and percentage change in LDL-C from baseline.
Absolute and percentage change in other lipids and lipoprotein from baseline.
Absolute and percentage change in other lipids and lipoproteins from baseline
Evaluate the effect of inclisiran on LDL-C levels
Evaluate the effect of inclisiran on total cholesterol (TC), triglycerides, LDL-C, and high density lipoprotein cholesterol (HDL-C)
Incidence of Adverse Events and Serious Adverse Events
Safety assessments including adverse events, serious adverse events, ECGs, concomitant medications, and safety laboratory parameters will be performed. The formation and further characterization of anti-drug antibodies will also be evaluated.
Day 1080
Percentage of subjects achieving prespecified LDL-C targets.
Proportion of subjects achieving prespecified LDL-C targets
Proportion of subjects reaching on treatment LDL-C targets of <100 mg/dL
Proportion of subjects reaching on treatment LDL-C targets of <70 mg/dL

Trial Safety

Safety Estimate

3 of 3
This is better than 85% of similar trials

Side Effects for

Saline Solution
Diabetes mellitus
14%
Hypertension
5%
Back pain
5%
Bronchitis
4%
Coronary artery disease
3%
Cardiac failure congestive
3%
Acute myocardial infarction
2%
Syncope
1%
Atrial fibrillation
1%
Myocardial infarction
1%
Non-cardiac chest pain
1%
Angina pectoris
1%
Ischaemic stroke
1%
Sepsis
1%
Ventricular tachycardia
1%
Pneumonia
1%
Lumbar spinal stenosis
1%
Angina unstable
1%
Atrioventricular block
0%
Clostridium difficile colitis
0%
Pneumonia bacterial
0%
Cardiomyopathy
0%
Atrioventricular block complete
0%
Haemorrhagic anaemia
0%
Cardio-respiratory arrest
0%
Ectopic hyperthyroidism
0%
Visual impairment
0%
Ophthalmic vein thrombosis
0%
Ventricular extrasystoles
0%
Gastrointestinal haemorrhage
0%
Cardiac failure acute
0%
Rectal haemorrhage
0%
Device related infection
0%
Intestinal ischaemia
0%
Cardiac failure
0%
Adenocarcinoma of colon
0%
Infectious colitis
0%
Osteomyelitis acute
0%
Osteomyelitis
0%
Periotinitis
0%
Craniocerebral injury
0%
Arthritis
0%
Foot fracture
0%
Post procedural hawmorrhage
0%
Post procedural haematuria
0%
Rib fracture
0%
Hypercalcaemia
0%
Hypoglycaemia
0%
Hypokalaemia
0%
Adenocarcinoma
0%
Colon cancer metastatic
0%
Spinal osteoarthritis
0%
Breast cancer
0%
Carcinoid tumour of the stomach
0%
Carotid artery stenosis
0%
Cerebrovascular disorder
0%
Spinal subdural haematoma
0%
Metastases to liver
0%
Squamous cell carcinoma of lung
0%
Gastritis erosive
0%
Supraventricular tachycardia
0%
Facial bones fracture
0%
Liposarcoma recurrent
0%
Colitis ischaemic
0%
Influenza
0%
Sensation of foreign body
0%
Cystitis
0%
Sepsis syndrome
0%
Head injury
0%
Subarachnoid haemorrhage
0%
Spinal column stenosis
0%
Bowen's disease
0%
Hepatic cancer
0%
Prostate cancer
0%
Post procedural infection
0%
Fluid overload
0%
Anal abscess
0%
Dehydration
0%
Escherichia bacteraemia
0%
Septic shock
0%
Contusion
0%
Cervical radiculopathy
0%
Cholecystitis acute
0%
Squamous cell carcinoma
0%
Urinary tract infection
0%
Tibia fracture
0%
Bladder cancer
0%
Arthralgia
0%
Fracture malunion
0%
Lung adenocarcinoma
0%
Musculoskeletal pain
0%
Osteoarthritis
0%
Acute myeloid leukaemia
0%
Breast cancer stage 1
0%
Endometrial cancer
0%
Gastrooesophageal cancer
0%
Demetia
0%
Retinal artery occlusion
0%
Malignant melanoma
0%
Prostate cancer recurrent
0%
Abdominal pain upper
0%
Diverticulum intestinal haemorrhagic
0%
Diarrhoea
0%
Upper gastrointestinal haemorrhage
0%
Chest pain
0%
Procedural pain
0%
Nerve compression
0%
Diabetes Mellitus
0%
Renal cancer
0%
Dizziness
0%
Diabetic ketoacidosis
0%
Vascular stent restenosis
0%
Staphylococcal abscess
0%
Joint dislocation
0%
Meningioma
0%
Myelodyplastic syndrome
0%
Non-small cell lung cancer
0%
Pancreatic carcinoma metastatic
0%
Renal cell carcinoma
0%
Carotid artery disease
0%
Cerebral infarction
0%
Hepatic cirrhosis
0%
Thoracic vertebral fracture
0%
Cerebral haemorrhage
0%
Pyrexia
0%
Subdural haemorrhage
0%
Cholelithiasis
0%
Appendicitis perforated
0%
Fall
0%
Hyponatraemia
0%
Rhabdomyolysis
0%
Metastases to central nervous system
0%
Pneumonia viral
0%
Wrist fracture
0%
Constipation
0%
Oesophageal varices haemorrhage
0%
Hypothermia
0%
Headache
0%
Anaemia
0%
Leukopenia
0%
Acute coronary syndrome
0%
Left ventricular failure
0%
Leukocytosis
0%
Intestinal obstruction
0%
Thrombocytopenia
0%
Pericardial effusion
0%
Cardiac arrest
0%
Ischaemic cardiomyopathy
0%
Mitral valve incompetence
0%
Pancreatitis
0%
Bradycardia
0%
Nodal arrythmia
0%
Palpitations
0%
Ventricular fibrillation
0%
Sinus node dysfunction
0%
Diverticulum
0%
Intestinal infarction
0%
Tachycardia
0%
Abdominal pain
0%
Duodenal polyp
0%
Enteritis
0%
Larger intestine perforation
0%
Gait disturbance
0%
Appendicitis
0%
Pancreatic mass
0%
Retroperitoneal haemorrhage
0%
Vomiting
0%
Small intestinal obstruction
0%
Ulcer haemorrhage
0%
Asthenia
0%
Multiple organ dysfunction syndrome
0%
Death
0%
Anaphylactic reaction
0%
Bacterial pyelonephritis
0%
Cholecystitis
0%
Diabetic foot infection
0%
Bile duct stone
0%
Arthritis infective
0%
Cavernous sinus thrombosis
0%
Gangrene
0%
Localised infection
0%
Cellulitis
0%
Diverticultis
0%
Gastroenteritis
0%
Gastroenteritis norovirus
0%
Periorbital cellulitis
0%
Pyelonephritis
0%
Cardiac valve replacement complication
0%
Chemical burn
0%
Postoperative wound infection
0%
Accidental overdose
0%
Cardiac contusion
0%
Hip fracture
0%
Femoral neck fracture
0%
Gun shot wound
0%
Humerus fracture
0%
Incisional hernia, obstructive
0%
Multiple injuries
0%
Lumbar vertebral fracture
0%
Occupational exposure to product
0%
Road traffic accident
0%
Spinal compression fracture
0%
Diabetes mellitus inadequate control
0%
Vascular pseudoaneurysm
0%
Blood pressure increased
0%
Gout
0%
Hyperglycaemia
0%
Hyperkalaemia
0%
Hypovolaemia
0%
Intervertebral disc degeneration
0%
Muscular weakness
0%
Cervical spinal stenosis
0%
Bladder transitional cell carcinoma
0%
Clear cell renal cell carcinoma
0%
Gastrointestinal lymphoma
0%
Invasive ductal breast carcinoma
0%
Squamous cell carcinoma of skin
0%
Cerebrovascular accident
0%
Hemiparesis
0%
Normal pressure hydrocephalus
0%
Metabolic encephalopathy
0%
Migraine
0%
Myelopathy
0%
Presyncope
0%
Radiculopathy
0%
Seizure
0%
Status migrainosus
0%
Arteriosclerosis coronary artery
0%
Atrial flutter
0%
Ventricular tachyarrhythmia
0%
Pericarditis
0%
Atrioventricular block second degree
0%
Atrial septal defect
0%
Anal fistula
0%
Coronary artery occlusion
0%
Iron deficiency anaemia
0%
This histogram enumerates side effects from a completed 2019 Phase 3 trial (NCT03399370) in the Saline Solution ARM group. Side effects include: Diabetes mellitus with 14%, Hypertension with 5%, Back pain with 5%, Bronchitis with 4%, Coronary artery disease with 3%.

Trial Design

2 Treatment Groups

Control
Inclisiran

This trial requires 3275 total participants across 2 different treatment groups

This trial involves 2 different treatments. Inclisiran Sodium is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 3 and have had some early promising results.

Inclisiran
Drug
Inclisiran sodium 300 milligrams (mg) will be administered as a single SC injection on Day 1*, 90, then every 180 days to Day 990. *Subjects who received blinded placebo in the feeder study will receive blinded inclisiran and subjects who received blinded inclisiran in the feeder study will receive blinded placebo on Day 1 in ORION-8. Subjects from the open label ORION-3 study will not receive any injection of study drug on Day 1. Their first dose of study medication will be at day 90
ControlNo treatment in the control group
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Inclisiran
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: day 1080
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly day 1080 for reporting.

Closest Location

Research Site 10001-027 - Pembroke Pines, FL

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. There are 3 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Completion on a previously qualifying inclisiran Phase II trial MDCO-PCS-16-01 (ORION-3), or Phase III lipid lowering ORION feeder study [MDCO-PCS-17-03 (ORION-9), MDCO-PCS-17-4 (ORION-10), or MDCO-PCS-17-08 (ORION-11)] meaning the subject received the last dose of study drug and completed the final study visit per applicable protocol.
On current lipid-lowering therapies (such as a statin and/or ezetimibe) from previous study with no planned medication or dose change during study participation.
Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

How many people get hypercholesterolemia a year in the United States?

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The lifetime risk of having this condition is 20.5% for men and 23.7% for women. The lifetime risk of developing heart disease is greater than 10% in both sexes.

Unverified Answer

What are the signs of hypercholesterolemia?

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Symptoms of the condition can be mild and easily overlooked. Hypercholesterolemia may become a serious problem as people get older. It can take time before symptoms are noticed and treatment can be started. Treatment options include weight control programmes on diet and exercise alone or combination of diet and medication. Hypercholesterolemia can be detected during screening tests before the condition progresses to heart disease.

Unverified Answer

What is hypercholesterolemia?

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These experiments revealed that the treatment with statins was beneficial to correct the dyslipidemia in this animal model of hypercholesterolemia. Data from a recent study shows that hypercholesterolemia affects lipid handling through a complex mechanism involving the regulation of genes controlling lipid catabolism and genes controlling lipid synthesis.

Unverified Answer

Can hypercholesterolemia be cured?

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Chronic (prolonged) hypercholesterolemia is not necessarily a curable disease but can be effectively controlled with appropriate therapy (e.g., statins, lifestyle modification, exercise, bariatric surgery, or weight loss) if patient readiness is obtained and motivation is maintained.

Unverified Answer

What causes hypercholesterolemia?

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Hypercholesterolemia is defined by the National Cholesterol Education Program as a total serum cholesterol level ≥ 200mg/dl (5.55 mmol/L) in men or ≥ 200mg/dl in women. It is estimated that 10 to 20% of men and 12%-24% of women have hypercholesterolemia. Although the exact cause is unknown, elevated production of cholesterol by the liver and/or other organs, and/or defects in its uptake or metabolism, along with low levels of high-density lipoprotein or other apolipoprotein particles, likely play a role.

Unverified Answer

What are common treatments for hypercholesterolemia?

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Hypercholesterolemia is commonly treated with lip- and statin-based prescription drug therapy, particularly statins such as atorvastatin or rosuvastatin. Also, dietary modification with low-fat diets supplemented with plant sterols for cholesterol lowering has been shown to reduce cholesterol levels, whereas fibrate medications are recommended only for those with very high cholesterol levels.

Unverified Answer

Is inclisiran sodium safe for people?

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Inclisiran sodium, an oral agent for the treatment of hypercholesterolemia, reduces LDL-cholesterol by 37% in adults. Its efficacy decreases with increasing age. The tolerability of inhalation-based inhalation formulations is promising, with minimal impact on QTc interval. Further study is required to confirm that inhaled agents are no more safety risks than oral agents.

Unverified Answer

Has inclisiran sodium proven to be more effective than a placebo?

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Results from a recent paper demonstrates that the use of Inclisiran sodium is more effective than a placebo, for the lowering of LDL cholesterol and TC. However, no difference in the effect on HDL cholesterol was found.

Unverified Answer

What are the common side effects of inclisiran sodium?

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Almost all patients reported headache and dizziness as the most common side effects. The common side effects of inclisiran sodium are as follows: dizziness, fatigue, and an itch. All of these are manageable with drug tapering.

Unverified Answer

What is the average age someone gets hypercholesterolemia?

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These data should not be used to determine at what age people should be screened for [hypercholesterolemia], because screening at 75 to 85 was associated with a 0.33 and 0.40 % prevalence of [high-density lipoprotein cholesterol]<35, 90 and 95 mg/dL in men and women, respectively. As people age, screening for [low-density lipoprotein cholesterol]<55 mg/dL will be more cost effective and may prevent unnecessary treatment and the associated costs.

Unverified Answer

Does hypercholesterolemia run in families?

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Families with a single affected member are similar at the level of lipid profile to families with an affected member and of similar phenotype and age, suggesting a multifactorial determinants of the lipid phenotype. Thus cholesterol levels are likely multifactorial, which should be expected as part of the natural history of this disease.

Unverified Answer

Have there been any new discoveries for treating hypercholesterolemia?

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There are a long list of treatments that offer hope to many patients with cholesterol problems; the list is never-ending. Although many of these treatments are not effective, one does stand out as the best-performing study of all: The pioglitazone [brand name Actos] study of patients with hypercholesterolemia. Since 2002, patients randomized to this drug regimen showed improvements on each of the major clinical outcomes studied. [Power(https://www.withpower.com/d/hypercholesterolemia-trials) offers a powerful resource to locate more recent studies on lipid-lowering treatment for patients with hypercholesterolemia.

Unverified Answer
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