Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia (ODYSSEY HIGH FH)

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01617655
First received: June 8, 2012
Last updated: December 23, 2015
Last verified: December 2015
Results First Received: August 20, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Hypercholesterolaemia
Interventions: Drug: Alirocumab
Drug: Placebo (for alirocumab)
Drug: Lipid Modifying Therapy (LMT)

  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 33 centers in 5 countries. A total of 206 participants were screened between June 2012 and May 2013, 99 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomization was stratified according to prior history of myocardial infarction (MI) or ischemic stroke, and intensity of statin treatment. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:2 ratio (placebo:alirocumab) after confirmation of selection criteria. 107 participants were randomized.

Reporting Groups
  Description
Placebo Q2W Placebo for alirocumab subcutaneous (SC) injection every two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.
Alirocumab 150 mg Q2W Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Participant Flow:   Overall Study
    Placebo Q2W     Alirocumab 150 mg Q2W  
STARTED     35 [1]   72 [1]
Treated     35     72  
COMPLETED     26     43  
NOT COMPLETED     9     29  
Adverse Event                 2                 3  
Poor compliance to protocol                 1                 4  
Participants moved                 0                 4  
Consent withdrawn by participant                 1                 1  
Last visit outside protocol visit window                 1                 10  
Site closure                 3                 5  
Other than specified above                 1                 2  
[1] Randomized



  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.
No text entered.

Reporting Groups
  Description
Placebo Q2W Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
Alirocumab 150 mg Q2W Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo Q2W     Alirocumab 150 mg Q2W     Total  
Number of Participants  
[units: participants]
  35     72     107  
Age  
[units: years]
Mean (Standard Deviation)
  52.1  (11.2)     49.8  (14.2)     50.6  (13.3)  
Gender  
[units: participants]
     
Female     13     37     50  
Male     22     35     57  
Calculated LDL-C in mg/dL [1]
[units: mg/dL]
Mean (Standard Deviation)
  201  (43.4)     196.3  (57.9)     197.8  (53.4)  
Calculated low density lipoprotein cholesterol (LDL-C) in mmol/L  
[units: mmol/L]
Mean (Standard Deviation)
  5.205  (1.125)     5.083  (1.499)     5.123  (1.382)  
[1] Calculated LDL-C from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/5]).



  Outcome Measures
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1.  Primary:   Percent Change From Baseline in Calculated LDL-C at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

2.  Secondary:   Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

3.  Secondary:   Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

4.  Secondary:   Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

5.  Secondary:   Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

6.  Secondary:   Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

7.  Secondary:   Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

8.  Secondary:   Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

9.  Secondary:   Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

10.  Secondary:   Percent Change From Baseline in Apo B at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

11.  Secondary:   Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

12.  Secondary:   Percent Change From Baseline in Total-C at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

13.  Secondary:   Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

14.  Secondary:   Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis   [ Time Frame: Up to Week 52 ]

15.  Secondary:   Percentage of Very High CV Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - On-Treatment Analysis   [ Time Frame: Up to Week 52 ]

16.  Secondary:   Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

17.  Secondary:   Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

18.  Secondary:   Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

19.  Secondary:   Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

20.  Secondary:   Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

21.  Secondary:   Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

22.  Secondary:   Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

23.  Secondary:   Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

24.  Secondary:   Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis   [ Time Frame: Up to Week 52 ]

25.  Secondary:   Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis   [ Time Frame: Up to Week 52 ]

26.  Other Pre-specified:   Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

27.  Other Pre-specified:   Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis   [ Time Frame: From Baseline to Week 78 ]

28.  Other Pre-specified:   Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 78 ]


  Serious Adverse Events


  Other Adverse Events


  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
Manual reclassification was done by the Sponsor for the "other reasons" of non-completion of study as specified in the electronic case report form (eCRF).


  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:
unchecked 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.
unchecked 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.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: Sanofi
e-mail: Contact­-US@sanofi.com


Publications:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01617655     History of Changes
Other Study ID Numbers: EFC12732
U1111-1128-5459 ( Other Identifier: UTN )
2012-001096-37 ( EudraCT Number )
Study First Received: June 8, 2012
Results First Received: August 20, 2015
Last Updated: December 23, 2015
Health Authority: United States: Food and Drug Administration