Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks. |
|
| Evolocumab 350 mg | Experimental | Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
| Evolocumab 420 mg | Experimental | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evolocumab | Biological | Administered by subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was measured using ultracentrifugation. | Baseline and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change From Baseline in LDL-C at Week 12 | LDL-C was measured using ultracentrifugation. | Baseline and Week 12 |
| Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23129602 | Background | 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. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
Not provided
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).
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks. |
| FG001 | Evolocumab 350 mg | Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| FG002 | Evolocumab 420 mg | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Full analysis set (all randomized participants who received at least 1 dose of investigational product).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks. |
| BG001 | Evolocumab 350 mg | Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was measured using ultracentrifugation. | Full analysis set; Missing ultracentrifugation (UC) LDL-C data at Week 12 were imputed using last observation carried forward (LOCF) and calculated LDL-C. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
|
12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 15.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 |
| ID | Term |
|---|---|
| D006938 | Hyperlipoproteinemia Type II |
| C566337 | Hypercholesterolemia, Autosomal Dominant, 3 |
| ID | Term |
|---|---|
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| C577155 | evolocumab |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Biological | d by subcutaneous injection |
|
| Baseline and Week 12 |
| Percent Change From Baseline in Apolipoprotein B at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12 | Baseline and Week 12 |
| BG002 | Evolocumab 420 mg | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Stratification Factor: LDL-C Level | Number | participants |
|
| Stratification Factor: Baseline Use Of Ezetimibe | Number | participants |
|
| LDL-C Concentration | LDL-C was measured using ultacentrifugation | Mean | Standard Deviation | mg/dL |
|
| Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration | Mean | Standard Deviation | mg/dL |
|
| Apolipoprotein B Concentration | Mean | Standard Deviation | mg/dL |
|
| Total Cholesterol/HDL-C Ratio | Mean | Standard Deviation | ratio |
|
| Apolipoprotein B/Apolipoprotein A1 Ratio | Mean | Standard Deviation | ratio |
|
| OG002 | Evolocumab 420 mg | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
|
|
|
| Secondary | Absolute Change From Baseline in LDL-C at Week 12 | LDL-C was measured using ultracentrifugation. | Full analysis set; LOCF imputation was used. | Posted | Least Squares Mean | Standard Error | mg/dL | Baseline and Week 12 |
|
|
|
|
| Secondary | Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Full analysis set; LOCF imputation was used. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
|
|
|
|
| Secondary | Percent Change From Baseline in Apolipoprotein B at Week 12 | Full analysis set; LOCF imputation was used | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
|
|
|
|
| Secondary | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | Full analysis set; LOCF imputaton was used. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
|
|
|
|
| Secondary | Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12 | Full analysis set; LOCF imputation was used. | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
|
|
|
|
| 0 |
| 56 |
| 24 |
| 56 |
| EG001 | Evolocumab 350 mg | Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | 0 | 55 | 22 | 55 |
| EG002 | Evolocumab 420 mg | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | 2 | 56 | 19 | 56 |
| Appendicitis | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Postoperative wound infection | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA 15.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Systematic Assessment |
|
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| D006951 | Hyperlipoproteinemias |
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| ANCOVA | ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates. | <0.001 | Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05. | LS Mean Treatment Difference | -84.7 | Standard Error of the Mean | 7.1 | 2-Sided | 95 | -98.8 | -70.7 | Placebo is the reference | Superiority or Other (legacy) |
| ANCOVA | ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates. | <0.001 | Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05. | LS Mean Treatment Difference | -53.46 | Standard Error of the Mean | 3.79 | 2-Sided | 95 | -60.95 | -45.97 | Placebo is the reference | Superiority or Other (legacy) |
| ANCOVA | ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates. | <0.001 | Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05. | LS Mean Treatment Difference | -46.20 | Standard Error of the Mean | 3.53 | 2-Sided | 95 | -53.18 | -39.23 | Placebo is the reference | Superiority or Other (legacy) |
| ANCOVA | ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates. | <0.001 | Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05. | LS Mean Treatment Difference | -45.01 | Standard Error of the Mean | 3.70 | 2-Sided | 95 | -52.32 | -37.70 | Placebo is the reference | Superiority or Other (legacy) |
| ANCOVA | ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates. | <0.001 | Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05. | LS Mean Treatment Difference | -44.64 | Standard Error of the Mean | 3.43 | 2-Sided | 95 | -51.41 | -37.86 | Placebo is the reference | Superiority or Other (legacy) |