Hypercholesterolemia, FamilialPhase 2RUTHERFORDNCT01375751
Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
A Phase 2 study testing Evolocumab in people with Hypercholesterolemia, Familial, run by Amgen.
Trial summary
The primary objective of this study was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145), compared with placebo, on percent change from baseline in LDL-C in adults with heterozygous familial hypercholesterolemia (HeFH). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hypercholesterolemia, Familial
- What is being tested?
- Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 168 participants
- Where
- No sites listed yet
- Study dates
- 2 Aug 2011to 16 May 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥ 18 to ≤ 75 years of age
- Diagnosis of heterozygous familial hypercholesterolemia by having met the diagnostic criteria outlined by the Simon Broome Register Group (Scientific Steering Committee 1991)
- On an approved statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks
- Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 100 mg/dL
- Fasting triglycerides ≤ 400 mg/dL
Who cannot join
- Homozygous familial hypercholesterolemia
- Low-Density Lipoprotein (LDL) or plasma apheresis within 12 months prior to randomization
- New York Heart Association (NYHA) III or IV heart failure, or known left ventricular ejection fraction < 30%
- Uncontrolled cardiac arrhythmia
- Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
- Type 1 diabetes; newly diagnosed or poorly controlled type 2 diabetes (HbA1c > 8.5%)
- Uncontrolled hypertension
About this study
Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Subject With Heterozygous Familial Hypercholesterolemia
The primary objective of this study was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145), compared with placebo, on percent change from baseline in LDL-C in adults with heterozygous familial hypercholesterolemia (HeFH).
- Conditions
- Hypercholesterolemia, Familial
- Being tested
- Evolocumab, Placebo
- Keywords
- Heterozygous Familial Hypercholesterolemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9)
- Medical subject headings
- Hyperlipoproteinemia Type II, Hypercholesterolemia, Autosomal Dominant, 3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabBiological
Also called AMG 145, Repatha
Administered by subcutaneous injection
PlaceboBiological
d by subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks. Receives: Biological: Placebo |
| Evolocumab 350 mg | Experimental | Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Receives: Biological: Evolocumab |
| Evolocumab 420 mg | Experimental | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Receives: Biological: Evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
LDL-C was measured using ultracentrifugation.
Measured: Baseline and Week 12
Secondary outcomes (5)
Absolute Change From Baseline in LDL-C at Week 12
LDL-C was measured using ultracentrifugation.
Measured: Baseline and Week 12
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2011 (estimated)
- Study start2 Aug 2011
- Primary completion16 May 2012
- Study completion16 May 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hypercholesterolemia, FamilialStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01375751
- Sponsor's protocol ID
- 20090158
- Acronym
- RUTHERFORD
- Status last verified
- Nov 2022
- First submitted
- 16 Jun 2011
- Last updated
- 15 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman SM, Stein EA. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation. 2012 Nov 13;126(20):2408-17. doi: 10.1161/CIRCULATIONAHA.112.144055. Epub 2012 Nov 5.
PubMed 23129602
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Subject With Heterozygous Familial Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT01375751
- Acronym / sponsor ID
- RUTHERFORD / 20090158
- Conditions
- Hypercholesterolemia, Familial
- Keywords
- Heterozygous Familial Hypercholesterolemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 2 Aug 2011 (actual)
- Primary completion
- 16 May 2012 (actual)
- Study completion
- 16 May 2012 (actual)
- First posted
- 17 Jun 2011 (estimated)
- Results
- Posted 29 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145), compared with placebo, on percent change from baseline in LDL-C in adults with heterozygous familial hypercholesterolemia (HeFH).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Biological: PlaceboParticipants received placebo subcutaneous injection once every 4 weeks for 12 weeks. |
| Evolocumab 350 mg | Experimental | Biological: EvolocumabParticipants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| Evolocumab 420 mg | Experimental | Biological: EvolocumabParticipants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female ≥ 18 to ≤ 75 years of age
- Diagnosis of heterozygous familial hypercholesterolemia by having met the diagnostic criteria outlined by the Simon Broome Register Group (Scientific Steering Committee 1991)
- On an approved statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks
- Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 100 mg/dL
- Fasting triglycerides ≤ 400 mg/dL
Key exclusion criteria (7 listed)
- Homozygous familial hypercholesterolemia
- Low-Density Lipoprotein (LDL) or plasma apheresis within 12 months prior to randomization
- New York Heart Association (NYHA) III or IV heart failure, or known left ventricular ejection fraction < 30%
- Uncontrolled cardiac arrhythmia
- Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvolocumabAlso: AMG 145, RepathaAdministered by subcutaneous injection | Biological | Evolocumab 350 mg, Evolocumab 420 mg |
| Placebod by subcutaneous injection | Biological | Placebo |
Primary outcome
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline and Week 12
LDL-C was measured using ultracentrifugation.
5 secondary outcomes
Absolute Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12
Time frame: Baseline and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23129602Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman SM, Stein EA. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation. 2012 Nov 13;126(20):2408-17. doi: 10.1161/CIRCULATIONAHA.112.144055. Epub 2012 Nov 5.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Evolocumab in people with Hypercholesterolemia, Familial, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01375751, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2022.