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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00607373
Other study ID # 301012CS5
Secondary ID 2005-003449-15
Status Completed
Phase Phase 3
First received January 22, 2008
Last updated October 27, 2014
Start date July 2007
Est. completion date March 2009

Study information

Verified date October 2014
Source Sanofi
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug AdministrationCanada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySouth Africa: Medicines Control CouncilSingapore: Health Sciences AuthorityTaiwan: Department of HealthBrazil: National Health Surveillance Agency
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of mipomersen (ISIS 301012) in subjects with homozygous familial hypercholesterolemia on lipid-lowering therapy.

This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period. Following treatment and Week 28 evaluations, participants could elect to enroll in an open-label extension study (301012-CS6; NCT00694109). Participants who were not eligible or elected not to enroll in the open-label extension study or who discontinued during the 28-week treatment period were followed in this study for 24 weeks from administration of the last dose of study drug.


Description:

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism characterized by markedly elevated low density lipoprotein (LDL), premature onset of atherosclerosis and development of xanthomata. Patients with homozygous familial hypercholesterolemia (HoFH) have a severe disease that presents in childhood with total cholesterol typically in the 650 to 1000 mg/dL range.

This was a randomized, double-blind, placebo-controlled study, which consisted of a 4-week screening period, 26 weeks of treatment, and a 24-week post- treatment follow-up period (with the exception of patients who enrolled in the open-label extension study, Study 301012-CS6; NCT00694109). Eligible patients were randomized in a 2:1 ratio to receive 200 mg mipomersen or matching volume placebo subcutaneous (SC) injections weekly. Patients who weighed <50 kg received a lower dose of 160 mg mipomersen or matching volume of placebo SC injections weekly. Patients were to have been on a stable (>=12 weeks) regimen of allowed lipid-lowering therapies at screening, and were required to remain on the same dose and regimen throughout the study.

Patients returned to the study center for clinical evaluation every other week during the first 4 weeks of treatment, once every 4 to 5 weeks for the remainder of the treatment period, and monthly during the post-treatment evaluation (follow-up) period. The primary endpoint assessment was at Week 28. Following treatment and Week 28 evaluations, eligible patients who tolerated the study drug could elect to enroll in the open-label extension study (Study 301012-CS6; NCT00694109). Patients who did not participate in the open-label extension study were required to return to the study center for clinical evaluation at least twice during the post-treatment follow-up period, including an end-of-study termination visit at the end of this 24-week period.


Recruitment information / eligibility

Status Completed
Enrollment 51
Est. completion date March 2009
Est. primary completion date March 2009
Accepts healthy volunteers No
Gender Both
Age group 12 Years and older
Eligibility Inclusion Criteria:

- Diagnosis of Homozygous Familial Hypercholesterolemia (HoFH)

- Stable lipid-lowering therapy for 12 weeks

- Stable weight for 6 weeks

- Stable low fat diet for 8 weeks

Exclusion Criteria:

- Significant health problems in the recent past including heart attack, stroke, blood disorders, cancer, or digestive problems

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

Drug:
mipomersen
200 mg mipomersen administered once a week for 26 weeks as a 1 mL subcutaneous injection. Subjects weighing less than 50 kg received a lower dose of 160 mg (0.8mL) mipomersen.
Placebo
1 mL subcutaneous injection once a week for 26 weeks. Subjects weighing less than 50 kg received 0.8 mL subcutaneous injection.

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
Genzyme, a Sanofi Company Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Singapore,  South Africa,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET) Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other Triglycerides at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET) Lipoprotein(a) was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET) VLDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other VLDL-C at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol (LDL-C) to High-density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) LDL-C and HDL-C were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET) Apo-A1 was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Other HDL-C at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Primary Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point LDL-C was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides <400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides >=400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. If the Study Day 1 and screening LDL-C values were >12% different (relative to the maximum value), then the screening value was not used, because the Study Day 1 value represents the best estimate of the patient's condition at the beginning of study drug administration. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Primary LDL-C at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Secondary Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point Apo-B was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Secondary Apo-B at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ) No
Secondary Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET) Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Secondary Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Secondary Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET) Non-HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
Secondary Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 No
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