Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study (RUTHERFORD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01375751
First received: June 16, 2011
Last updated: August 28, 2015
Last verified: August 2015
Results First Received: August 28, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Hypercholesterolemia, Familial
Interventions: Biological: Evolocumab
Biological: 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

Men and women 18 to to 75 years of age, with a diagnosis of heterozygous familial hypercholesterolemia, fasting low-density lipoprotein cholesterol (LDL-C) of ≥ 100 mg/dL, and fasting triglycerides ≤ 400 mg/dL were eligible for this study.

The first patient was enrolled on 02 August 2011 and the last patient was enrolled on 20 February 2012.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomization was stratified on the basis of screening LDL-C level (< 130 mg/dL [3.4 mmol/L] or ≥ 130 mg/dL) and ezetimibe use at baseline (yes or no).

Reporting Groups
  Description
Placebo Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 350 mg Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Participant Flow:   Overall Study
    Placebo     Evolocumab 350 mg     Evolocumab 420 mg  
STARTED     56     56     56  
Received Treatment     56     55     56  
COMPLETED     56     55     56  
NOT COMPLETED     0     1     0  
Other                 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.
Full analysis set (all randomized participants who received at least 1 dose of investigational product).

Reporting Groups
  Description
Placebo Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 350 mg Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo     Evolocumab 350 mg     Evolocumab 420 mg     Total  
Number of Participants  
[units: participants]
  56     55     56     167  
Age  
[units: years]
Mean (Standard Deviation)
  49.3  (11.3)     47.6  (13.6)     51.8  (13.0)     49.6  (12.7)  
Gender  
[units: participants]
       
Female     32     25     21     78  
Male     24     30     35     89  
Race/Ethnicity, Customized  
[units: participants]
       
Hispanic or Latino     2     0     0     2  
Not Hispanic or Latino     54     55     56     165  
Race/Ethnicity, Customized  
[units: participants]
       
Asian     3     1     3     7  
Black or African American     0     3     1     4  
White     48     48     52     148  
Other     4     3     0     7  
Mixed Race     1     0     0     1  
Stratification Factor: LDL-C Level  
[units: participants]
       
< 130 mg/dL     19     17     19     55  
≥ 130 mg/dL     37     38     37     112  
Stratification Factor: Baseline Use Of Ezetimibe  
[units: participants]
       
    20     19     20     59  
Yes     36     36     36     108  
LDL-C Concentration [1]
[units: mg/dL]
Mean (Standard Deviation)
  160.8  (44.0)     156.8  (46.1)     149.5  (36.3)     155.7  (42.3)  
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  182.7  (52.6)     178.0  (51.7)     171.0  (43.6)     177.2  (49.4)  
Apolipoprotein B Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  125.2  (30.3)     120.9  (29.3)     119.3  (27.6)     121.8  (29.0)  
Total Cholesterol/HDL-C Ratio  
[units: ratio]
Mean (Standard Deviation)
  4.895  (1.790)     5.119  (1.923)     4.857  (1.688)     4.956  (1.795)  
Apolipoprotein B/Apolipoprotein A1 Ratio  
[units: ratio]
Mean (Standard Deviation)
  0.899  (0.277)     0.901  (0.286)     0.867  (0.264)     0.899  (0.274)  
[1] LDL-C was measured using ultacentrifugation



  Outcome Measures
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1.  Primary:   Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12   [ Time Frame: Baseline and Week 12 ]

2.  Secondary:   Absolute Change From Baseline in LDL-C at Week 12   [ Time Frame: Baseline and Week 12 ]

3.  Secondary:   Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12   [ Time Frame: Baseline and Week 12 ]

4.  Secondary:   Percent Change From Baseline in Apolipoprotein B at Week 12   [ Time Frame: Baseline and Week 12 ]

5.  Secondary:   Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12   [ Time Frame: Baseline and Week 12 ]

6.  Secondary:   Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12   [ Time Frame: Baseline and Week 12 ]


  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
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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:
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: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


Publications:

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01375751     History of Changes
Other Study ID Numbers: 20090158
Study First Received: June 16, 2011
Results First Received: August 28, 2015
Last Updated: August 28, 2015
Health Authority: Hong Kong: Department of Health
Netherlands:Centrale Commissie Mensgebonden Onderzoek (CCMO)
Norway: Norwegian Medicines Agency
Singapore: Health Science Authority
South Africa: Medicines Control Council
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Canada: Health Canada
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe