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Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy (ODYSSEY FH I)

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01623115
First received: June 15, 2012
Last updated: January 11, 2016
Last verified: January 2016
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: Hypercholesterolemia
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 89 centers in 14 countries. A total of 597 participants were screened between July 2012 and April 2013, 111 of whom were screen failures.

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 or ischemic stroke, intensity of statin treatment & geographic region. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in 1:2 (placebo:alirocumab) after confirmation of selection criteria. 486 participants were randomized.

Reporting Groups
  Description
Placebo Placebo for alirocumab subcutaneous (SC) injection every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.
Alirocumab 75 mg/Up to 150 mg Q2W Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥ 70 mg/dL (1.81 mmol/L) at Week 8.

Participant Flow:   Overall Study
    Placebo     Alirocumab 75 mg/Up to 150 mg Q2W  
STARTED     163 [1]   323 [1]
Treated     163     322  
COMPLETED     130     246  
NOT COMPLETED     33     77  
Randomized but not treated                 0                 1  
Physician Decision                 1                 0  
Participants moved                 1                 5  
Adverse Event                 10                 13  
Poor compliance to protocol                 4                 10  
Consent withdrawn by participant                 2                 6  
Related to study drug administration                 0                 2  
Last visit outside protocol visit window                 14                 26  
Site closure                 1                 7  
Death                 0                 4  
Other than specified above                 0                 3  
[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 Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
Alirocumab 75 mg/Up to 150 mg Q2W Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) at Week 8.
Total Total of all reporting groups

Baseline Measures
    Placebo     Alirocumab 75 mg/Up to 150 mg Q2W     Total  
Number of Participants  
[units: participants]
  163     323     486  
Age  
[units: years]
Mean (Standard Deviation)
  51.7  (12.3)     52.1  (12.9)     51.9  (12.7)  
Gender  
[units: participants]
     
Female     69     143     212  
Male     94     180     274  
Calculated LDL-C in mg/dL [1]
[units: mg/dL]
Mean (Standard Deviation)
  144.4  (46.8)     144.8  (51.1)     144.6  (49.7)  
Calculated LDL-C in mmol/L  
[units: mmol/L]
Mean (Standard Deviation)
  3.739  (1.213)     3.749  (1.325)     3.746  (1.287)  
[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 - Intent-to-Treat (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:   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 ]

17.  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 ]

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

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

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

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

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

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

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

25.  Secondary:   Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis   [ Time Frame: From Baseline 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 of Results:
Other Publications:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01623115     History of Changes
Other Study ID Numbers: EFC12492
U1111-1121-4275 ( Other Identifier: UTN )
2011-005109-56 ( EudraCT Number )
Study First Received: June 15, 2012
Results First Received: August 20, 2015
Last Updated: January 11, 2016
Health Authority: United States: Food and Drug Administration