ORION-9: Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH)

• Sponsor: The Medicines Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03397121
• Collaborator: (none)
• Enrollment: 482
• Locations: 45
• Arms: 2
• Actual Duration (Months): 21.6
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Heterozygous Familial Hypercholesterolemia; Elevated Cholesterol	Drug: Inclisiran; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 482 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• 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).
• Actual Study Start Date: Nov 28, 2017
• Actual Primary Completion Date: Aug 27, 2019
• Actual Study Completion Date: Sep 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Inclisiran Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90 then every 6 months.	Drug: Inclisiran; Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
Placebo Comparator: Placebo Placebo will be administered as SC injections of saline solution on Day 1, Day 90 then every 6 months.	Drug: Placebo; Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).; Other Names: Saline Solution

Outcome Measures

Primary Outcome Measures

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

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

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

Secondary Outcome Measures

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

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

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

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

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

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

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Participants may be included if they meet all of the following inclusion criteria prior to randomization:

1. Male or female participants ≥18 years of age.

2. 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.

3. Serum LDL-C ≥2.6 millimoles (mmol)/liter (L) (≥100 mg/dL) at screening.

4. Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.

5. Participants on statins should be receiving a maximally tolerated dose.

6. Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.

7. 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.

Exclusion Criteria:

Participants will be excluded from the study if any of the following exclusion criteria apply immediately prior to randomization:

1. New York Heart Association (NYHA) class IV heart failure.

2. Uncontrolled cardiac arrhythmia

3. Uncontrolled severe hypertension

4. Active liver disease

5. 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:

6. Women >2 years postmenopausal (defined as 1 year or longer since last menstrual period) AND more than 55 years of age.

7. Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization.

8. Women who are surgically sterilized at least 3 months prior to enrollment.

9. Males who are unwilling to use an acceptable method of birth control during the entire study period (condom with spermicide).

10. Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.

11. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 90001-005	Mission Viejo	California	United States	92691
2	Site 90001-001	Newport Beach	California	United States	92663
3	Site 90001-015	Stanford	California	United States	94305
4	Site 90001-047	Boca Raton	Florida	United States	33434
5	Site 90001-004	Boston	Massachusetts	United States	02114
6	Site 90001-056	Saint Paul	Minnesota	United States	55102
7	Site 90001-012	Butte	Montana	United States	59701
8	Site 90001-112	Las Vegas	Nevada	United States	89119
9	Site 90001-014	Summit	New Jersey	United States	07901
10	Site 90001-002	Cincinnati	Ohio	United States	45227
11	Site 90011-005	Chicoutimi	Quebec	Canada	G7H 7K9
12	Site 90011-001	Montréal	Quebec	Canada	H2W 1R7
13	Site 90011-002	Quebec City	Quebec	Canada	G1V 4W2
14	Site 90420-001	Prague		Czechia	140 21
15	Site 90420-006	Prague		Czechia	180 00
16	Site 90420-005	Trutnov		Czechia	541 01
17	Site 90045-001	Aalborg		Denmark	DK-9000
18	Site 90045-004	Esbjerg		Denmark	DK-6700
19	Site 90045-003	Herning		Denmark	7400
20	Site 90045-006	Hvidovre		Denmark	2650
21	Site 90045-002	Roskilde		Denmark	DK-4000
22	Site 90045-005	Viborg		Denmark	DK-8800
23	Site 90031-001	Amersfoort		Netherlands	3813 TZ
24	Site 90031-003	Amsterdam		Netherlands	1105 AZ
25	Site 90031-009	Hoorn		Netherlands	1624 NP
26	Site 90031-006	Tilburg		Netherlands	5042 AD
27	Site 90031-005	Utrecht		Netherlands	3584 CX
28	Site 90027-004	Cape Town	Western Cape	South Africa	7130
29	Site 90027-003	Bloemfontein		South Africa	9301
30	Site 90027-005	Cape Town		South Africa	7130
31	Site 90027-001	Cape Town		South Africa	7500
32	Site 90027-008	Cape Town		South Africa	7530
33	Site 90027-010	Johannesburg		South Africa	2193
34	Site 90027-007	Pretoria		South Africa	0157
35	Site 90027-006	Pretoria		South Africa	0184
36	Site 90027-009	Witbank		South Africa	1035
37	Site 90034-003	A Coruña		Spain	15006
38	Site 90034-005	Barcelona		Spain
39	Site 90034-004	Córdoba		Spain	14004
40	Site 90034-006	L'Hospitalet De Llobregat		Spain	8907
41	Site 90034-001	Reus		Spain	43204
42	Site 90034-002	Zaragoza		Spain	50009
43	Site 90046-002	Göteborg		Sweden	SE-41345
44	Site 90046-001	Stockholm		Sweden	SE-11157
45	Site 90046-003	Stockholm		Sweden	SE-14186

Sponsors and Collaborators

• The Medicines Company

Investigators

• Principal Investigator: Frederick J. Raal, MD, University of Witwatersrand, South Africa

Study Documents (Full-Text)

• Study Protocol - Jan 31, 2019
• Statistical Analysis Plan - Sep 13, 2019

More Information

Publications

None provided.

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT03397121
• Other Study ID Numbers: MDCO-PCS-17-03; 2017-002472-30
• First Posted: Jan 11, 2018
• Last Update Posted: Oct 28, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by The Medicines Company: HeFH; LDL-C; Inclisiran
• Additional relevant MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia

Study Results

Participant Flow

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90 then every 6 months. Inclisiran: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Placebo will be administered as SC injections of saline solution on Day 1, Day 90 then every 6 months. Placebo: Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Period Title: Overall Study
STARTED	242	240
COMPLETED	235	231
NOT COMPLETED	7	9

Baseline Characteristics

Arm/Group Title	Inclisiran	Placebo	Total
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90 then every 6 months. Inclisiran: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Placebo will be administered as SC injections of saline solution on Day 1, Day 90 then every 6 months. Placebo: Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).	Total of all reporting groups
Overall Participants	242	240	482
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	189 78.1%	185 77.1%	374 77.6%
>=65 years	53 21.9%	55 22.9%	108 22.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.4 (12.48)	55.0 (11.81)	54.7 (12.14)
Sex: Female, Male (Count of Participants)
Female	130 53.7%	125 52.1%	255 52.9%
Male	112 46.3%	115 47.9%	227 47.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 2.9%	8 3.3%	15 3.1%
Not Hispanic or Latino	235 97.1%	232 96.7%	467 96.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.4%	0 0%	1 0.2%
Asian	7 2.9%	5 2.1%	12 2.5%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.4%	1 0.2%
Black or African American	8 3.3%	7 2.9%	15 3.1%
White	226 93.4%	227 94.6%	453 94%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	12 5%	11 4.6%	23 4.8%
Netherlands	19 7.9%	19 7.9%	38 7.9%
Sweden	18 7.4%	16 6.7%	34 7.1%
United States	33 13.6%	32 13.3%	65 13.5%
Czechia	7 2.9%	5 2.1%	12 2.5%
Denmark	23 9.5%	26 10.8%	49 10.2%
South Africa	88 36.4%	89 37.1%	177 36.7%
Spain	42 17.4%	42 17.5%	84 17.4%

Outcome Measures

1. Primary Outcome

Title	Percent Change in LDL-C From Baseline To Day 510
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) Population

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Measure Participants	242	240
Least Squares Mean (95% Confidence Interval) [percent change]	-41.15	8.37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-49.52
	Confidence Interval	(2-Sided) 95%; -55.04 to -43.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	Represents the least squares mean difference from Placebo

2. Primary Outcome

Title	Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 540
Description	Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 90 reported
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) Population

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Measure Participants	242	240
Least Squares Mean (95% Confidence Interval) [percent change]	-38.08	6.22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-44.30
	Confidence Interval	(2-Sided) 95%; -48.48 to -40.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Represents the least squares mean difference from Placebo

3. Secondary Outcome

Title	Absolute Change in LDL-C From Baseline to Day 510
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) Population

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Measure Participants	242	240
Least Squares Mean (95% Confidence Interval) [mg/dL]	-58.95	9.94

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-68.89
	Confidence Interval	(2-Sided) 95%; -77.11 to -60.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Represents the least squares mean difference from Placebo

4. Secondary Outcome

Title	Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540
Description	Assessments performed at Baseline, Day 90, Day 540, absolute change at Day 90 reported
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) Population

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Measure Participants	242	240
Least Squares Mean (95% Confidence Interval) [mg/dL]	-56.58	6.17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-62.74
	Confidence Interval	(2-Sided) 95%; -69.01 to -56.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Represents the least squares mean difference from Placebo

5. Secondary Outcome

Title	Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) Population

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Measure Participants	242	240
Least Squares Mean (95% Confidence Interval) [percent change]	-60.68	17.66

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-78.34
	Confidence Interval	(2-Sided) 95%; -83.65 to -73.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Represents the least squares mean difference from Placebo

6. Secondary Outcome

Title	Percentage Change in Total Cholesterol From Baseline to Day 510
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) Population

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.s.	Placebo administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Measure Participants	242	240
Least Squares Mean (95% Confidence Interval) [percent change]	-25.11	6.66

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	LS Mean Difference (95% CI) from Placebo
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-31.77
	Confidence Interval	(2-Sided) 95%; -35.59 to -27.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	Represents the least squares mean difference from Placebo

7. Secondary Outcome

Title	Percent Change in Apolipoprotein B (Apo-B) From Baseline To Day 510
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) Population

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Measure Participants	242	240
Least Squares Mean (95% Confidence Interval) [percent change]	-33.14	2.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-36.06
	Confidence Interval	(2-Sided) 95%; -39.99 to -32.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Represents the least squares mean difference from Placebo

8. Secondary Outcome

Title	Percent Change in Non-high-density Lipoprotein (HDL)-C From Baseline To Day 510
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) Population

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Measure Participants	242	240
Least Squares Mean (95% Confidence Interval) [percent change]	-34.93	7.43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-42.36
	Confidence Interval	(2-Sided) 95%; -47.32 to -37.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Represents the least squares mean difference from Placebo

Adverse Events

Time Frame	Day 0 - 510
Adverse Event Reporting Description	The safety population for adverse event collection was 481 subjects which is different from the Intent-to-Treat (ITT) population used in efficacy analysis (482 subjects). One subject was randomized in the Inclisiran arm, but never received study drug, therefore this subject not included in the safety population.
Arm/Group Title	Inclisiran		Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90 then every 6 months. Inclisiran: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.		Placebo will be administered as SC injections of saline solution on Day 1, Day 90 then every 6 months. Placebo: Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
All Cause Mortality
	Inclisiran		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/241 (0.4%)		1/240 (0.4%)
Serious Adverse Events
	Inclisiran		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/241 (7.5%)		33/240 (13.8%)
Cardiac disorders
Acute myocardial infarction	2/241 (0.8%)		1/240 (0.4%)
Angina Pectoris	1/241 (0.4%)		0/240 (0%)
Angina unstable	1/241 (0.4%)		4/240 (1.7%)
Aortic valve stenosis	2/241 (0.8%)		0/240 (0%)
Arteriosclerosis coronary artery	0/241 (0%)		1/240 (0.4%)
Atrial fibrillation	0/241 (0%)		1/240 (0.4%)
Cardiac arrest	1/241 (0.4%)		0/240 (0%)
Cardiac failure	1/241 (0.4%)		0/240 (0%)
Cardiac failure acute	1/241 (0.4%)		0/240 (0%)
Coronary artery disease	1/241 (0.4%)		0/240 (0%)
Myocardial infarction	1/241 (0.4%)		0/240 (0%)
Myocardial ischaemia	1/241 (0.4%)		3/240 (1.3%)
Supraventricular tachycardia	0/241 (0%)		1/240 (0.4%)
Eye disorders
Optic ischaemic neuropathy	0/241 (0%)		2/240 (0.8%)
Gastrointestinal disorders
Gastritis erosive	0/241 (0%)		1/240 (0.4%)
Pancreatitis acute	0/241 (0%)		1/240 (0.4%)
General disorders
Hernia	0/241 (0%)		1/240 (0.4%)
Non-cardiac chest pain	0/241 (0%)		1/240 (0.4%)
Hepatobiliary disorders
Biliary colic	0/241 (0%)		1/240 (0.4%)
Infections and infestations
Cellulitis	1/241 (0.4%)		0/240 (0%)
Diverticulitis	0/241 (0%)		1/240 (0.4%)
Infective tenosynovitis	1/241 (0.4%)		0/240 (0%)
Influenza	0/241 (0%)		1/240 (0.4%)
Pneumonia	1/241 (0.4%)		1/240 (0.4%)
Post procedural infection	0/241 (0%)		1/240 (0.4%)
Pyelitis	0/241 (0%)		1/240 (0.4%)
Pyelonephritis	0/241 (0%)		1/240 (0.4%)
Tick-borne fever	0/241 (0%)		1/240 (0.4%)
Viral upper respiratory tract infection	0/241 (0%)		1/240 (0.4%)
Wound sepsis	0/241 (0%)		1/240 (0.4%)
Injury, poisoning and procedural complications
Limb injury	0/241 (0%)		1/240 (0.4%)
Post procedural haematuria	0/241 (0%)		1/240 (0.4%)
Road traffic accident	0/241 (0%)		1/240 (0.4%)
Soft tissue injury	0/241 (0%)		1/240 (0.4%)
Spinal compression fracture	1/241 (0.4%)		0/240 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/241 (0%)		2/240 (0.8%)
Myalgia	0/241 (0%)		1/240 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma	0/241 (0%)		1/240 (0.4%)
Malignant melanoma in situ	0/241 (0%)		1/240 (0.4%)
Prostate cancer	1/241 (0.4%)		0/240 (0%)
Squamous cell carcinoma of skin	1/241 (0.4%)		1/240 (0.4%)
Nervous system disorders
Sensory disturbance	0/241 (0%)		1/240 (0.4%)
Trigeminal neuralgia	0/241 (0%)		1/240 (0.4%)
Product Issues
Device loosening	1/241 (0.4%)		0/240 (0%)
Psychiatric disorders
Anxiety	1/241 (0.4%)		0/240 (0%)
Depression	0/241 (0%)		1/240 (0.4%)
Major depression	0/241 (0%)		1/240 (0.4%)
Renal and urinary disorders
Hydronephrosis	0/241 (0%)		1/240 (0.4%)
Nephrolithiasis	0/241 (0%)		1/240 (0.4%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/241 (0%)		1/240 (0.4%)
Chronic obstructive pulmonary disease	0/241 (0%)		1/240 (0.4%)
Other (Not Including Serious) Adverse Events
	Inclisiran		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/241 (39.8%)		67/240 (27.9%)
General disorders
Injection site reaction	22/241 (9.1%)		0/240 (0%)
Infections and infestations
Influenza	13/241 (5.4%)		21/240 (8.8%)
Nasopharyngitis	28/241 (11.6%)		20/240 (8.3%)
Upper respiratory tract infection	16/241 (6.6%)		16/240 (6.7%)
Musculoskeletal and connective tissue disorders
Back pain	17/241 (7.1%)		10/240 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.