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
  Purpose
The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneously once every 2 weeks (Q2W) and once monthly (QM), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH).

Condition Intervention Phase
Hyperlipidemia
Biological: Evolocumab
Drug: Placebo
Phase 3

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
Official Title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Subjects With Heterozygous Familial Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percent Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Non-HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Lipoprotein (a) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Triglycerides at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in VLDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Enrollment: 331
Study Start Date: February 2013
Study Completion Date: December 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Drug: Placebo
Administered by subcutaneous injection
Placebo Comparator: Placebo QM
Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
Drug: Placebo
Administered by subcutaneous injection
Experimental: Evolocumab Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha
Experimental: Evolocumab QM
Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female ≥ 18 to ≤ 80 years of age
  • Diagnosis of heterozygous familial hypercholesterolemia
  • On a stable dose of an approved statin and lipid regulating medication
  • Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L)
  • Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion Criteria:

  • Homozygous familial hypercholesterolemia
  • LDL or plasma apheresis
  • New York Heart Association (NYHA) III or IV heart failure
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled hypertension
  • Type 1 diabetes, poorly controlled type 2 diabetes
  • Uncontrolled hypothyroidism or hyperthyroidism
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763918

  Hide Study Locations
Locations
United States, Arizona
Research Site
Scottsdale, Arizona, United States, 85258
United States, Ohio
Research Site
Cincinnati, Ohio, United States, 45227
Australia, New South Wales
Research Site
Camperdown, New South Wales, Australia, 2015
Australia, Western Australia
Research Site
Perth, Western Australia, Australia, 6000
Canada, British Columbia
Research Site
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Ontario
Research Site
London, Ontario, Canada, N6A 5K8
Canada, Quebec
Research Site
Chicoutimi, Quebec, Canada, G7H 7K9
Research Site
Montreal, Quebec, Canada, H3A 1A1
Research Site
Montreal, Quebec, Canada, H2W 1R7
France
Research Site
Bron, France, 69677
Research Site
Nantes Cedex 1, France, 44093
Research Site
Paris Cedex 13, France, 75651
Germany
Research Site
Köln, Germany, 50937
Hong Kong
Research Site
New Territories, Hong Kong
Netherlands
Research Site
Amersfoort, Netherlands, 3813 TZ
Research Site
Amsterdam, Netherlands, 1091 AC
Research Site
Amsterdam, Netherlands, 1105 AZ
Research Site
Gouda, Netherlands, 2803 HH
Research Site
Groningen, Netherlands, 9713 GZ
Research Site
Hoorn, Netherlands, 1625 HV
Research Site
Tilburg, Netherlands, 5022 GC
Research Site
Utrecht, Netherlands, 3584 CX
New Zealand
Research Site
Christchurch, New Zealand, 8011
Norway
Research Site
Oslo, Norway, 0373
South Africa
Research Site
Johannesburg, Gauteng, South Africa, 2193
Research Site
Midrand, Gauteng, South Africa, 1685
Research Site
Observatory, Western Cape, South Africa, 7925
Research Site
Parow, Western Cape, South Africa, 7505
Spain
Research Site
Cordoba, Andalucía, Spain, 14004
Research Site
Zaragoza, Aragón, Spain, 50009
Research Site
Reus, Cataluña, Spain, 43204
Research Site
Madrid, Spain, 28040
Sweden
Research Site
Stockholm, Sweden, 111 35
Research Site
Stockholm, Sweden, 141 86
Switzerland
Research Site
Reinach, Switzerland, 4153
United Kingdom
Research Site
Coventry, United Kingdom, CV2 2DX
Research Site
London, United Kingdom, SE1 7EH
Research Site
London, United Kingdom, W6 8RF
Research Site
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01763918     History of Changes
Other Study ID Numbers: 20110117  2012-001365-32 
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

Keywords provided by Amgen:
High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Hyperlipoproteinemia Type II
Dyslipidemias
Genetic Diseases, Inborn
Hyperlipoproteinemias
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Metabolic Diseases
Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on February 11, 2016