Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2 (RUTHERFORD-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01763918
First received: January 7, 2013
Last updated: November 18, 2015
Last verified: November 2015
Results First Received: September 2, 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: Hyperlipidemia
Interventions: Biological: Evolocumab
Drug: Placebo

  Participant Flow
  Hide Participant Flow

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 80 years old with a diagnosis of heterozygous familial hypercholesterolemia (HeFH) on stable doses of an approved statin with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL were eligible for this study. The first participant enrolled on 07 February 2013 and the last participant enrolled 03 September 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants received subcutaneous placebo corresponding to the once monthly dose volume during a 6-week screening period. Those who completed the screening period and met final eligibility criteria were randomized 1:1:2:2 into 4 treatment groups. Randomization was stratified by LDL-C level (< 160 mg/dL vs ≥ 160 mg/dL) and ezetimibe use.

Reporting Groups
  Description
Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Placebo QM Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Participant Flow:   Overall Study
    Placebo Q2W     Placebo QM     Evolocumab Q2W     Evolocumab QM  
STARTED     55     55     111     110  
Received Treatment     54     55     110     110  
COMPLETED     49     54     101     108  
NOT COMPLETED     6     1     10     2  
Withdrawal by Subject                 2                 1                 1                 2  
Sponsor Decision                 4                 0                 9                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

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 Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Placebo QM Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo Q2W     Placebo QM     Evolocumab Q2W     Evolocumab QM     Total  
Number of Participants  
[units: participants]
  55     55     111     110     331  
Age  
[units: years]
Mean (Standard Deviation)
  51.1  (14.1)     46.8  (12.1)     52.3  (12.6)     51.9  (12.0)     51.1  (12.7)  
Gender  
[units: participants]
         
Female     25     24     45     46     140  
Male     30     31     66     64     191  
Race/Ethnicity, Customized  
[units: participants]
         
American Indian or Alaska Native     0     0     0     0     0  
Asian     1     3     4     8     16  
Black or African American     1     0     1     1     3  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0  
White     51     49     100     98     298  
Other     2     3     6     3     14  
Race/Ethnicity, Customized  
[units: participants]
         
Hispanic or Latino     1     0     0     1     2  
Not Hispanic or Latino     54     55     111     109     329  
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level  
[units: participants]
         
< 160 mg/dL     35     35     70     70     210  
≥ 160 mg/dL     20     20     41     40     121  
Baseline Ezetimibe Use  
[units: participants]
         
No     22     21     43     43     129  
Yes     33     34     68     67     202  
LDL-C Concentration [1]
[units: mg/dL]
Mean (Standard Deviation)
  151.1  (36.5)     151.5  (42.5)     161.4  (51.0)     153.6  (43.3)     155.5  (44.9)  
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration [2]
[units: mg/dL]
Mean (Standard Deviation)
  175.4  (43.9)     175.4  (45.9)     187.4  (56.7)     178.5  (45.8)     180.4  (49.5)  
Apolipoprotein B Concentration [2]
[units: mg/dL]
Mean (Standard Deviation)
  114.3  (29.8)     110.3  (21.7)     119.0  (30.7)     114.9  (25.5)     115.4  (27.5)  
Total cholesterol/HDL-C Ratio [2]
[units: ratio]
Mean (Standard Deviation)
  4.695  (1.905)     4.844  (1.435)     5.159  (2.031)     4.842  (1.801)     4.924  (1.845)  
Apolipoprotein B/Apolipoprotein A1 Ratio [2]
[units: ratio]
Mean (Standard Deviation)
  0.815  (0.264)     0.851  (0.249)     0.888  (0.322)     0.850  (0.331)     0.857  (0.305)  
Lipoprotein(a) Concentration [2]
[units: nmol/L]
Median (Inter-Quartile Range)
  44.0  
  (24.0 to 105.0)  
  87.0  
  (36.0 to 219.0)  
  77.5  
  (29.0 to 205.5)  
  61.0  
  (17.0 to 194.0)  
  65.0  
  (25.0 to 199.0)  
Triglyceride Concentration [2]
[units: mg/dL]
Median (Inter-Quartile Range)
  95.8  
  (74.5 to 143.0)  
  102.0  
  (79.0 to 151.0)  
  118.5  
  (86.5 to 160.5)  
  112.5  
  (84.5 to 156.5)  
  110.0  
  (81.5 to 154.0)  
Very Low-Density Lipoprotein Cholesterol (VLDL-C) Concentration [2]
[units: mg/dL]
Mean (Standard Deviation)
  23.1  (10.7)     23.9  (10.5)     25.9  (11.8)     24.9  (11.7)     24.8  (11.4)  
HDL-C Concentration [2]
[units: mg/dL]
Mean (Standard Deviation)
  53.2  (16.5)     49.1  (12.7)     50.4  (16.1)     51.9  (16.0)     51.1  (15.6)  
[1]

Data are provided for the full analysis set (all randomized participants who received at least

1 dose of investigational product)

[2] Data are provided for the full analysis set



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent Change From Baseline in LDL-C at Week 12   [ Time Frame: Baseline and Week 12 ]

2.  Primary:   Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

3.  Secondary:   Change From Baseline in LDL-C at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

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

5.  Secondary:   Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)   [ Time Frame: Weeks 10 and 12 ]

6.  Secondary:   Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12   [ Time Frame: Week 12 ]

7.  Secondary:   Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

8.  Secondary:   Percent Change From Baseline in Non-HDL-C at Week 12   [ Time Frame: Baseline and Week 12 ]

9.  Secondary:   Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

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

11.  Secondary:   Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

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

13.  Secondary:   Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

14.  Secondary:   Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12   [ Time Frame: Baseline and Week 12 ]

15.  Secondary:   Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

16.  Secondary:   Percent Change From Baseline in Lipoprotein (a) at Week 12   [ Time Frame: Baseline and Week 12 ]

17.  Secondary:   Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

18.  Secondary:   Percent Change From Baseline in Triglycerides at Week 12   [ Time Frame: Baseline and Week 12 ]

19.  Secondary:   Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

20.  Secondary:   Percent Change From Baseline in HDL-C at Week 12   [ Time Frame: Baseline and Week 12 ]

21.  Secondary:   Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

22.  Secondary:   Percent Change From Baseline in VLDL-C at Week 12   [ Time Frame: Baseline and Week 12 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information
  Hide More Information

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: NCT01763918     History of Changes
Other Study ID Numbers: 20110117
2012-001365-32 ( EudraCT Number )
Study First Received: January 7, 2013
Results First Received: September 2, 2015
Last Updated: November 18, 2015
Health Authority: South Africa: Medicines Control Council
United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Medsafe
Norway: Norwegian Medicines Agency
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Hong Kong: Department of Health
Canada: Health Canada
Spain: Agencia Española de Medicamentos y Productos Sanitarios