Alirocumab in Patients With Acute Myocardial Infarction

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02938949
• Collaborator: Regeneron Pharmaceuticals (Industry), Sanofi (Industry)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 19.4
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Phase IV investigator initiated clinical trial to study the effectiveness of alirocumab, an inhibitor of proprotein convertase subtilisin/kexin (PCSK9), versus placebo added to high-intensity statin (atorvastatin 80 mg) in lowering low density lipoprotein (LDL) cholesterol during non-ST segment elevation myocardial infarction (NSTEMI).

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction; Hypercholesterolemia	Drug: alirocumab; Drug: placebo	Phase 4

Detailed Description

This research will study the effects of early initiation of alirocumab in addition to high intensity statin therapy in patients who have previously been treated with high intensity statins with poor response, who present with a type I (spontaneous) acute NSTEMI. Patients will be dosed with drug or placebo once during the first day of their hospital admission. Blood samples will be collected at baseline, 3 days and 14 days after randomization for biomarker testing. Particular attention will be paid to additional LDL lowering effects, as well as the effects on PCSK9 levels and inflammatory biomarkers. Safety and tolerability will be monitored with complete blood count + differential and complete metabolic panels at each study visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Alirocumab in Patients With Acute Myocardial Infarction: A Randomized Controlled Double-Blinded Study
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Aug 1, 2018
• Actual Study Completion Date: Aug 16, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Alirocumab Alirocumab (150 mg) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin.	Drug: alirocumab; Other Names: Praluent
Placebo Comparator: placebo Placebo (sterile saline) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin.	Drug: placebo

Outcome Measures

Primary Outcome Measures

1. Changes in Low-density Lipoprotein (LDL) Cholesterol [baseline and 14 days]

   Placebo-corrected percentage change in calculated LDL cholesterol from baseline to day 14

Secondary Outcome Measures

1. Change in Inflammatory Markers (hsCRP) [baseline to 3 days]

   Placebo-corrected percentage change in inflammatory markers (hsCRP) from baseline to 3 days

2. Change in Inflammatory Markers (hsCRP) [baseline to 14 days]

   Placebo-corrected Percentage Change in Inflammatory Markers (hsCRP) From Baseline to 14 Days

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Acute type I (spontaneous) NSTEMI defined as chest pain (or equivalent) with an onset of symptoms within 12 hours of presentation, a duration of >15 minutes, and elevated cardiac troponin I levels, with or without electrocardiographic changes [with the exclusion of ST elevation];

2. On medical therapy with high intensity statin prior to admission (either atorvastatin 40-80 mg or rosuvastatin 20-40 mg) as documented by hospital or pharmacy records and with known LDL cholesterol ≥70 mg/dL within the prior 12 months.

Exclusion Criteria:

1. Age <21 years of age

2. Inability to give informed consent

3. Previous, current or planned treatment with a PCSK9 inhibitor

4. Known history of loss of function of PCSK9 (genetic mutation or sequence variation)

5. Patient with homozygous familial hypercholesterolemia (clinically or by previous genotyping)

6. Recent (<14 days) or active use of immunosuppressive drugs (including but not limited to high-dose corticosteroids [>1mg/kg of prednisone equivalent], Tumor Necrosis Factor-α blockers, cyclosporine) not including non-steroidal antinflammatory drugs or corticosteroids used for IV dye allergy or corticosteroids used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to randomization (note: topical, intra-articular, nasal, inhaled, and ophthalmic steroid therapies are not considered "systemic" and are allowed);

7. Chronic auto-immune or auto-inflammatory disease (including but not limited to rheumatoid arthritis, systemic lupus erythematosus);

8. History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer;

9. Known chronic hepatitis B or C infection (excluding patients with a positive antibody who were successfully treated or who have demonstrated no viral load);

10. Known human immunodeficiency virus infection.

11. Use of fibrates other than fenofibrate within 6 weeks of the screening visit.

12. Uncontrolled hypothyroidism. Note: patients on thyroid replacement therapy can be included if the dosage of thyroxin has been stable for at least 12 weeks prior to screening.

13. Known history of a hemorrhagic stroke.

14. Has been previously treated with at least 1 dose of alirocumab or any other anti-PCSK9 monoclonal antibody in other clinical studies.

15. Conditions/situations such as:

16. Any clinically significant abnormality identified at the time of screening that in the judgment of the investigator or any sub-investigator would preclude safe completion of the study or constrain assessment of endpoints, such as major systemic diseases or patients with short life expectancy.

17. Patients considered by the investigator or any sub-investigator to be inappropriate for this study for any reason:

1. Those patients deemed unable to meet specific protocol requirements, such as scheduled visits.

1. Those patients the investigator deems unable to administer or tolerate long-term injections.

1. Investigator or any sub-investigator, pharmacist, study coordinator, other study staff, or relative thereof directly involved in the conduct of the protocol.

2. Presence of any other conditions (geographic or social), actual or anticipated, that the investigator feels would restrict or limit the patient's participation for the duration of the study.

1. Thyroid-stimulating hormone (TSH) < lower limit of normal (LLN) or > upper limit of normal (ULN); if TSH is abnormal due to controlled hypothyroidism (patient is on a stable dose of thyroid replacement therapy), the patient may be enrolled into the study;

2. Exclusion Criteria Related to the Active Comparator and/or Mandatory Background Therapies: All contraindications to the background therapies or warnings/precautions of use (when appropriate) as displayed in the respective national product labeling.

3. Exclusion Criteria Related to the Current Knowledge of Alirocumab

4. Known hypersensitivity to monoclonal antibody therapeutics

5. Pregnant or breastfeeding women

6. Women of childbearing potential who are not protected by highly effective method(s) of birth control throughout the entire duration of study treatment and for 10 weeks after the last dose of study drug and/or who are unwilling or unable to be tested for pregnancy.

7. Men capable of impregnating women who are not protected by highly effective method(s) of birth control and/or who are unwilling to use an effective contraceptive method throughout the entire duration of study treatment and for 10 weeks after the last dose of study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Virginia Commonwealth University	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• Virginia Commonwealth University
• Regeneron Pharmaceuticals
• Sanofi

Investigators

• Principal Investigator: Antonio Abbate, MD, PhD, Virginia Commonwealth University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 1, 2017

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT02938949
• Other Study ID Numbers: HM20008008
• First Posted: Oct 19, 2016
• Last Update Posted: Sep 6, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Virginia Commonwealth University: Myocardial Infarction; Low Density Lipoprotein Cholesterol; proprotein convertase subtilisin kexin 9, human; alirocumab
• Additional relevant MeSH terms: Myocardial Infarction; Hypercholesterolemia; Infarction

Study Results

Participant Flow

Arm/Group Title	Alirocumab	Placebo
Arm/Group Description	Alirocumab (150 mg) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. alirocumab	Placebo (sterile saline) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. placebo
Period Title: Overall Study
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Alirocumab	Placebo	Total
Arm/Group Description	Alirocumab (150 mg) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. alirocumab	Placebo (sterile saline) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. placebo	Total of all reporting groups
Overall Participants	10	10	20
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	60	56	59
Sex: Female, Male (Count of Participants)
Female	4 40%	9 90%	13 65%
Male	6 60%	1 10%	7 35%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 70%	9 90%	16 80%
White	3 30%	1 10%	4 20%
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]
United States	10 100%	10 100%	20 100%
body mass index (kilograms per meters squared) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kilograms per meters squared]	27.8	31.9	30.9

Outcome Measures

1. Primary Outcome

Title	Changes in Low-density Lipoprotein (LDL) Cholesterol
Description	Placebo-corrected percentage change in calculated LDL cholesterol from baseline to day 14
Time Frame	baseline and 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alirocumab	Placebo
Arm/Group Description	Alirocumab (150 mg) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. alirocumab	Placebo (sterile saline) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. placebo
Measure Participants	10	10
Median (Inter-Quartile Range) [percent change]	-73	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Change in Inflammatory Markers (hsCRP)
Description	Placebo-corrected percentage change in inflammatory markers (hsCRP) from baseline to 3 days
Time Frame	baseline to 3 days

Outcome Measure Data

Analysis Population Description

Research team was unable to collect samples from 2 Alirocumab participants.

Arm/Group Title	Alirocumab	Placebo
Arm/Group Description	Alirocumab (150 mg) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. alirocumab	Placebo (sterile saline) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. placebo
Measure Participants	8	10
Median (Inter-Quartile Range) [percent change]	58	55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	> 0.20
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Change in Inflammatory Markers (hsCRP)
Description	Placebo-corrected Percentage Change in Inflammatory Markers (hsCRP) From Baseline to 14 Days
Time Frame	baseline to 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alirocumab	Placebo
Arm/Group Description	Alirocumab (150 mg) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. alirocumab	Placebo (sterile saline) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. placebo
Measure Participants	10	10
Median (Inter-Quartile Range) [percent change]	-4	-33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alirocumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.20
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	From baseline to 14 days
Arm/Group Title	Alirocumab		Placebo
Arm/Group Description	Alirocumab (150 mg) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. alirocumab		Placebo (sterile saline) will be administered by subcutaneous injection once, within the first day of the patient's diagnosis of NSTEMI. Patients will also receive an 80 mg dose of atorvastatin. placebo
All Cause Mortality
	Alirocumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Alirocumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		1/10 (10%)
Cardiac disorders
admission for heart failure	2/10 (20%)	2	0/10 (0%)	0
admission for unstable angina	1/10 (10%)	1	0/10 (0%)	0
Infections and infestations
sepsis	0/10 (0%)	0	1/10 (10%)	1
Nervous system disorders
stroke	1/10 (10%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Alirocumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.