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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-005399-40 | EudraCT Number |
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A study to determine the safety, tolerability, and efficacy of evolocumab (AMG 145) in patients with homozygous familial hypercholesterolemia (HoFH).
Study Masking:
Part A: Open Label Part B: Double Blind
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Evolocumab | Experimental | Participants received open-label evolocumab 420 mg subcutaneously once a month for 12 weeks. |
|
| Part B: Evolocumab | Experimental | Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks. |
|
| Part B: Placebo | Placebo Comparator | Participants received double-blind placebo subcutaneously once a month for 12 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evolocumab | Biological | Administered by subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was quantified using the ultracentrifugation method. | Baseline and Week 12 |
| Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was quantified using the ultracentrifugation method. | Baseline and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Change From Baseline in LDL-C at Week 12 | LDL-C was quantified using the ultracentrifugation method. | Baseline and Week 12 |
| Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | New York | New York | 10032 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29353350 | Background | Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7. | |
| 25282520 | Derived | Raal FJ, Honarpour N, Blom DJ, Hovingh GK, Xu F, Scott R, Wasserman SM, Stein EA; TESLA Investigators. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jan 24;385(9965):341-50. doi: 10.1016/S0140-6736(14)61374-X. Epub 2014 Oct 1. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
Not provided
Part A was an open-label, single-arm, multicenter pilot study. Part B was a double-blind, randomized, placebo-controlled, multicenter study with expanded enrollment. In Part B participants were randomized in a 1:2 allocation stratified on the basis of screening low-density lipoprotein cholesterol (LDL-C) (< 420 mg/dL vs ≥ 420 mg/dL).
Male and female adults and adolescents ages ≥ 12 to ≤ 65 years (≥ 12 to ≤ 80 years in Part B) with a diagnosis of homozygous familial hypercholesterolemia (HoFH) were eligible for this study. The first participant enrolled on 05 April 2012 and the last participant enrolled on 08 November 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: Evolocumab | Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks. |
| FG001 | Part B: Placebo | Participants received double-blind placebo subcutaneously once a month for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo | Drug | Administered by subcutaneous injection |
|
| Baseline and Week 12 |
| Part A: Percent Change From Baseline in Apolipoprotein B at Week 12 | Baseline and Week 12 |
| Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | Baseline and Week 12 |
| Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | Baseline and Week 12 |
| Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12 | LDL-C was quantified using the ultracentrifugation method. | Baseline and Week 12 |
| Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12 | Baseline and Week 12 |
| Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12 | LDL-C was quantified using the ultracentrifugation method. | Baseline and Weeks 6 and 12 |
| Part B: Percent Change From Baseline in Apolipoprotein B at Week 12 | Baseline and Week 12 |
| Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12 | Baseline and Weeks 6 and 12 |
| Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12 | Baseline and Week 12 |
| Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12 | Baseline and Weeks 6 and 12 |
| Cincinnati |
| Ohio |
| 45227 |
| United States |
| Research Site | Brussels | 1200 | Belgium |
| Research Site | La Louvière | 7100 | Belgium |
| Research Site | London | Ontario | N6A 5K8 | Canada |
| Research Site | Chicoutimi | Quebec | G7H 7K9 | Canada |
| Research Site | Brno | 656 91 | Czechia |
| Research Site | Hradec Králové | 500 05 | Czechia |
| Research Site | Uherské Hradiště | 686 01 | Czechia |
| Research Site | Dijon | 21000 | France |
| Research Site | Paris | 75651 | France |
| Research Site | New Territories | Hong Kong |
| Research Site | Pisa | 56124 | Italy |
| Research Site | Beirut | 0000 | Lebanon |
| Research Site | Amsterdam | 1105 AZ | Netherlands |
| Research Site | Christchurch | 8011 | New Zealand |
| Research Site | Johannesburg | Gauteng | 2193 | South Africa |
| Research Site | Observatory | Western Cape | 7925 | South Africa |
| Research Site | Córdoba | Andalusia | 14004 | Spain |
| Research Site | Lugo | Galicia | 27003 | Spain |
| Research Site | Madrid | 28040 | Spain |
| 24014831 | Derived | Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013 Nov 5;128(19):2113-20. doi: 10.1161/CIRCULATIONAHA.113.004678. Epub 2013 Sep 6. |
| FG002 | Part B: Evolocumab | Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks. |
| Received Treatment |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: Evolocumab | Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks. |
| BG001 | Part B: Placebo | Participants received double-blind placebo subcutaneously once a month for 12 weeks. |
| BG002 | Part B: Evolocumab | Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level | Participants in Part A were not stratified based on LDL-C level. | Number | participants |
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| LDL-C Concentration | LDL-C was quantified using the ultracentrifugation method. Data are provided for the full analysis set (all enrolled participants who received at least 1 dose of evolocumab (Part A) or all randomized participants who received at least 1 dose of investigational product (Part B). | Mean | Standard Deviation | mg/dL |
| ||||||||||||||
| Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration | Data are provided for the full analysis set | Mean | Standard Deviation | mg/dL |
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| Apolipoprotein B Concentration | Data are provided for the full analysis set | Mean | Standard Deviation | mg/dL |
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| Total Cholesterol/HDL-C Ratio | Data are provided for the full analysis set | Mean | Standard Deviation | ratio |
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| Apolipoprotein B/Apolipoprotein A1 Ratio | Data are provided for the full analysis set | Mean | Standard Deviation | ratio |
| ||||||||||||||
| Lipoprotein(a) Concentration | Median | Inter-Quartile Range | nmol/L |
| |||||||||||||||
| Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration | Data are provided for the full analysis set | Mean | Standard Deviation | ng/mL |
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| 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 | Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was quantified using the ultracentrifugation method. | Part A full analysis set (all enrolled participants who received at least 1 dose of evolocumab) | Posted | Mean | Standard Error | percent change | Baseline and Week 12 |
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| Secondary | Part A: Change From Baseline in LDL-C at Week 12 | LDL-C was quantified using the ultracentrifugation method. | Part A full analysis set | Posted | Mean | Standard Error | mg/dL | Baseline and Week 12 |
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| ||||||||||||||||||||||||||
| Secondary | Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | Part A full analysis set | Posted | Mean | Standard Error | percent change | Baseline and Week 12 |
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| Secondary | Part A: Percent Change From Baseline in Apolipoprotein B at Week 12 | Part A full analysis set | Posted | Mean | Standard Error | percent change | Baseline and Week 12 |
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| Secondary | Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | Part A full analysis set | Posted | Mean | Standard Error | percent change | Baseline and Week 12 |
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| Secondary | Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | Part A full analysis set | Posted | Mean | Standard Error | percent change | Baseline and Week 12 |
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| Secondary | Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12 | LDL-C was quantified using the ultracentrifugation method. | Part A full analysis set | Posted | Number | percentage of participants | Baseline and Week 12 |
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| Secondary | Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12 | Part A full analysis set | Posted | Mean | Standard Error | ng/mL | Baseline and Week 12 |
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| ||||||||||||||||||||||||||
| Secondary | Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12 | LDL-C was quantified using the ultracentrifugation method. | Part B full analysis set | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Weeks 6 and 12 |
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| Secondary | Part B: Percent Change From Baseline in Apolipoprotein B at Week 12 | Part B full analysis set | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
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| Secondary | Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12 | Part B full analysis set | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Weeks 6 and 12 |
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| Secondary | Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12 | Part B full anlaysis set | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
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| Secondary | Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12 | Part B full analysis set | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Weeks 6 and 12 |
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| Primary | Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was quantified using the ultracentrifugation method. | Part B full analysis set (all enrolled participants who received at least 1 dose of investigational product) | Posted | Least Squares Mean | Standard Error | percent change | Baseline and Week 12 |
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|
12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A: OL Evolocumab | Participants received open-label (OL) evolocumab 420 mg subcutaneously once a month for 12 weeks. | 0 | 8 | 4 | 8 | ||
| EG001 | Part B: DB Placebo | Participants received double-blind (DB) placebo subcutaneously once a month for 12 weeks. | 0 | 16 | 10 | 16 | ||
| EG002 | Part B: DB Evolocumab | Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks. | 0 | 33 | 11 | 33 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Medical device site reaction | General disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 16.0/16.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 16.0/16.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 16.0/16.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 16.0/16.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 16.0/16.1 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 16.0/16.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 16.0/16.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/16.1 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 |
| ID | Term |
|---|---|
| D000090542 | Homozygous Familial Hypercholesterolemia |
| D006937 | Hypercholesterolemia |
| D006938 | Hyperlipoproteinemia Type II |
| ID | Term |
|---|---|
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006951 | Hyperlipoproteinemias |
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C577155 | evolocumab |
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| Male |
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| Asian |
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| Black or African American |
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| Native Hawaiian or Other Pacific Islander |
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| White |
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| Other |
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| Not Hispanic or Latino |
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| ≥ 420 mg/dL |
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| Missing |
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