Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01763918 | Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2 | PHASE3 | COMPLETED | 331 | — | — | Feb 7, 2013 | Dec 19, 2013 | Jun 17, 2019 | 39 | United States, Australia +12 |
| NCT01763905 | Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2 | PHASE3 | COMPLETED | 307 | — | — | Jan 24, 2013 | Nov 19, 2013 | Jul 20, 2020 | 58 | United States, Australia +12 |
| NCT01763827 | Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 | PHASE3 | COMPLETED | 615 | — | — | Jan 21, 2013 | Oct 29, 2013 | Nov 8, 2022 | 83 | United States, Australia +8 |
| NCT01763866 | LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2 | PHASE3 | COMPLETED | 2,067 | — | — | Jan 15, 2013 | Dec 4, 2013 | Nov 8, 2022 | 244 | United States, Australia +19 |
| NCT01375764 | Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects | PHASE2 | COMPLETED | 160 | — | — | Jul 28, 2011 | May 8, 2012 | Nov 7, 2022 | 42 | United States, Australia +6 |
| NCT01375777 | Monoclonal Antibody Against PCSK9 to Reduce Elevated Low-density Lipoprotein Cholesterol (LDL-C) in Adults Currently Not Receiving Drug Therapy for Easing Lipid Levels | PHASE2 | COMPLETED | 411 | — | — | Jul 6, 2011 | Mar 2, 2012 | Nov 8, 2022 | 58 | United States, Australia +3 |
| NCT01380730 | LAPLACE-TIMI 57: Low-density Lipoprotein Cholesterol (LDL-C) Assessment With PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy | PHASE2 | COMPLETED | 631 | — | — | Jul 1, 2011 | Apr 5, 2012 | Nov 15, 2022 | 100 | United States, Canada +3 |
| NCT02275156 | Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab | PHASE1 | COMPLETED | 18 | — | — | Aug 19, 2014 | Dec 19, 2014 | Nov 7, 2022 | 1 | United States |
| NCT01133522 | Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Evolocumab (AMG 145) in Adults With Hyperlipidemia on Stable Doses of a Statin | PHASE1 | COMPLETED | 60 | — | — | Jun 1, 2010 | Sep 14, 2011 | Nov 2, 2018 | - | — |
LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.
Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) of the assay was 800 ng/mL.
The relationship of each adverse event to the investigational product was assessed by the investigator. A serious adverse event (SAE) is defined as an adverse event that * is fatal * is life threatening (places the subject at immediate risk of death) * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * other significant medical hazard.
Serum samples were analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-evolocumab binding antibodies. Positive samples were subsequently tested in a receptor-ligand binding bioassay for anti-evolocumab neutralizing antibodies
| Arm | Type | Description |
|---|---|---|
| Placebo Q2W | PLACEBO_COMPARATOR | Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. |
| Placebo QM | PLACEBO_COMPARATOR | Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. |
| Evolocumab Q2W | EXPERIMENTAL | Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. |
| Evolocumab QM | EXPERIMENTAL | Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. |
| Ezetimibe (Q2W) | ACTIVE_COMPARATOR | Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. |
| Ezetimibe (QM) | ACTIVE_COMPARATOR | Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. |
| A10 PBO Q2W | PLACEBO_COMPARATOR | Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. |
| A10 PBO QM | PLACEBO_COMPARATOR | Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. |
| A10 EZE (Q2W) | ACTIVE_COMPARATOR | Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once a day for up to 12 weeks. |
| A10 EZE (QM) | ACTIVE_COMPARATOR | Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. |
| A10 EvoMab Q2W | EXPERIMENTAL | Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. |
| A10 EvoMab QM | EXPERIMENTAL | Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks |
| A80 PBO Q2W | PLACEBO_COMPARATOR | Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. |
| A80 PBO QM | PLACEBO_COMPARATOR | Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month and placebo tablets once a day for up to 12 weeks. |
| A80 EZE (Q2W) | ACTIVE_COMPARATOR | Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. |
| A80 EZE (QM) | ACTIVE_COMPARATOR | Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. |
| A80 EvoMab Q2W | EXPERIMENTAL | Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. |
| A80 EvoMab QM | EXPERIMENTAL | Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks. |
| R5 PBO Q2W | PLACEBO_COMPARATOR | Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. |
| R5 PBO QM | PLACEBO_COMPARATOR | Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks. |
| R5 EvoMab Q2W | EXPERIMENTAL | Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. |
| R5 EvoMab QM | EXPERIMENTAL | Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. |
| R40 PBO Q2W | PLACEBO_COMPARATOR | Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. |
| R40 PBO QM | PLACEBO_COMPARATOR | Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks. |
| R40 EvoMab Q2W | EXPERIMENTAL | Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. |
| R40 EvoMab QM | EXPERIMENTAL | Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. |
| S40 PBO Q2W | PLACEBO_COMPARATOR | Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. |
| S40 PBO QM | PLACEBO_COMPARATOR | Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks. |
| S40 EvoMab Q2W | EXPERIMENTAL | Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. |
| S40 EvoMab QM | EXPERIMENTAL | Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. |
| Ezetimibe | ACTIVE_COMPARATOR | Participants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks. |
| Evolocumab + Ezetimibe | EXPERIMENTAL | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks. |
| Evolocumab 280 mg | EXPERIMENTAL | Participants received 280 mg evolocumab by 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. |
| Placebo Q4W | PLACEBO_COMPARATOR | Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. |
| Evolocumab 70 mg Q2W | EXPERIMENTAL | Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. |
| Evolocumab 105 mg Q2W | EXPERIMENTAL | Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. |
| Evolocumab 140 mg Q2W | EXPERIMENTAL | Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. |
| Evolocumab 280 mg Q4W | EXPERIMENTAL | Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| Evolocumab 350 mg Q4W | EXPERIMENTAL | Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| Evolocumab 420 mg Q4W | EXPERIMENTAL | Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. |
| Evolocumab | EXPERIMENTAL | Participants received a single 140 mg dose of evolocumab subcutaneously on Day 1. |
| Placebo | PLACEBO_COMPARATOR | Participants received matching placebo dose regimens by subcutaneous injection. |
| Name | Type | Description |
|---|---|---|
| Evolocumab | BIOLOGICAL | Administered by subcutaneous injection |
| Placebo | DRUG | Administered by subcutaneous injection |
| Placebo to Evolocumab | DRUG | Subcutaneous injection |
| Ezetimibe | DRUG | Tablet for oral administration |
| Placebo to Ezetimibe | DRUG | Tablet for oral administration |
| Atorvastatin | DRUG | Administered orally once a day |
| Rosuvastatin | DRUG | Administered orally once a day |
| Simvastatin | DRUG | Administered orally once a day |
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 Crit...