Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Hypercholesterolemia
Interventions:	Drug: Alirocumab; Drug: Placebo

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 16 centers in the United States of America and Canada. Overall, 118 participants were screened between January 2011 and June 2011.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomization was stratified by concomitant use of ezetimibe (Yes/No). Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1:1:1:1 ratio after confirmation of selection criteria. 77 participants were randomized.

Reporting Groups

	Description
Placebo	Placebo subcutaneous (SC) injection once every two weeks (Q2W) added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 150 mg Q4W	Alirocumab 150 mg SC injection once every 4 weeks (Q4W) added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 200 mg Q4W	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 300 mg Q4W	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.

Participant Flow:   Overall Study

	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W
STARTED	15	15	16	15	16
COMPLETED	15	15	16	14	16
NOT COMPLETED	0	0	0	1	0
Adverse Event	0	0	0	1	0

  Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
Placebo	Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 150 mg Q4W	Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 200 mg Q4W	Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 300 mg Q4W	Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Total	Total of all reporting groups

Baseline Measures

	Placebo	Alirocumab 150 mg Q4W	Alirocumab 200 mg Q4W	Alirocumab 300 mg Q4W	Alirocumab 150 mg Q2W	Total
Overall Participants Analyzed; [Units: Participants]	15	15	16	15	16	77
Age; [Units: Years]; Mean (Standard Deviation)	51.9 (9.6)	51.3 (7.7)	52.9 (11.2)	54.3 (9.6)	56.3 (10.2)	53.4 (9.7)
Gender; [Units: Participants]
Female	6	6	7	8	3	30
Male	9	9	9	7	13	47
Low Density Lipoprotein Cholesterol (LDL-C) in mg/dL [1]; [Units: mg/dL]; Mean (Standard Deviation)	150.8 (34.0)	166.7 (50.1)	169.8 (57.0)	139.6 (24.7)	147.2 (32.6)	154.9 (42.1)
[1] Calculated LDL-C from Friedewald formula.

  Outcome Measures

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1. Primary:

Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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2. Secondary:

Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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3. Secondary:

Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis [ Time Frame: Week 12 (LOCF) ]

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4. Secondary:

Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis [ Time Frame: Week 12 (LOCF) ]

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5. Secondary:

Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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6. Secondary:

Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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7. Secondary:

Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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8. Secondary:

Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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9. Secondary:

Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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10. Secondary:

Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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11. Secondary:

Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 ]

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12. Secondary:

Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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13. Secondary:

Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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14. Secondary:

Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 ]

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15. Secondary:

Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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16. Secondary:

Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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17. Secondary:

Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 ]

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18. Secondary:

Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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19. Secondary:

Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ]

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  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information

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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.

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.

Results Point of Contact:  

Name/Title: Clinical Trial Management
Organization: Regeneron Pharmaceuticals, Inc
e-mail: clinicaltrials@regeneron.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J Clin Lipidol. 2017 Nov - Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4.

Toth PP, Hamon SC, Jones SR, Martin SS, Joshi PH, Kulkarni KR, Banerjee P, Hanotin C, Roth EM, McKenney JM. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo. Lipids Health Dis. 2016 Feb 13;15:28. doi: 10.1186/s12944-016-0197-4.

Stein EA, Gipe D, Bergeron J, Gaudet D, Weiss R, Dufour R, Wu R, Pordy R. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet. 2012 Jul 7;380(9836):29-36. doi: 10.1016/S0140-6736(12)60771-5. Epub 2012 May 26.

Responsible Party:	Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01266876 History of Changes
Other Study ID Numbers:	R727-CL-1003
First Submitted:	December 23, 2010
First Posted:	December 24, 2010
Results First Submitted:	August 20, 2015
Results First Posted:	September 22, 2015
Last Update Posted:	September 22, 2015