Ignite Creation Date:
2024-05-05 @ 5:00 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00362180
Status:
COMPLETED
Last Update Posted:
2016-10-21
First Post:
2006-08-07
Brief Title:
Measure Liver Fat Content After ISIS 301012 Mipomersen Administration
Sponsor:
Kastle Therapeutics LLC
Organization:
Kastle Therapeutics LLC
Study Overview
Official Title:
A Phase 2 Randomized Double-Blind Placebo-Controlled Study to Evaluate the Effect of Apolipoprotein BApoB Reduction by ISIS 301012 on Liver Triglyceride Content in Subjects With Varying Degrees of Hyperlipidemia
Status:
COMPLETED
Status Verified Date:
2016-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will assess what if any effect that ISIS 301012 mipomersen has on liver triglyceride content in multiple groups of subjects with varying degrees of risk for hepatic steatosis In order to enroll subject groups with varying degrees of risk the study has included multiple cohorts Cohorts A-G Additions and removal of cohorts has been accomplished with protocol amendments
Detailed Description:
This was a randomized double-blind placebo-controlled study to measure the effect of treatment with mipomersen on liver triglyceride TG content in patients with varying degrees of hyperlipidemia and risk for hepatic steatosis
The original study design included 4 cohorts Cohorts A through D Subsequent protocol amendments added 3 cohorts Cohorts E F and G to the study truncated the enrollment of Cohort D and eliminated Cohorts B and C The study consisted of up to a 3-week screening period a 4-week Cohorts A and D 13-week Cohort E or 52-week Cohort G treatment period and a 20-week post-treatment follow-up period Cohort F was an observational cohort and therefore was not treated with study drug Patients in this cohort underwent a 15-week Magnetic resonance spectroscopy MRS and ultrasound evaluation period
The study cohorts are
Cohort A Healthy volunteers with LDL-C 140 mgdL 36 mmolL serum TG 200 mgdL 23 mmolL hemoglobin A1c HbA1c 60 and hepatic TG content 5 as measured by MRS at screening Patients were randomized to mipomersen 200 mg or placebo and treated for 4 weeks
Cohorts BC were eliminated in a protocol amendment prior to enrolling any patients and are not discussed further
Cohort D In an amendment to the protocol Cohort D was closed to enrollment One patient had already been enrolled in the study prior to the amendment The patient enrolled in this cohort had impaired fasting glucose defined as fasting blood glucose 6 mmolL and 7 mmolL and mixed dyslipidemia LDL-C 215 mgdL 56 mmolL and serum TG 200 mgdL 23 mmolL The patient was treated with mipomersen 200 mg for 4 weeks
Cohort E Patients with uncomplicated heterozygous familial hypercholesterolemia HeFH Alanine aminotransferase ALT 15 upper limit of normal Upper limit of normal ULN no evidence of insulin resistance or metabolic syndrome and hepatic TG content 5 by MRS at screening Patients were to remain on their baseline statin ezetimibe regimen but were to wash out from other lipid-lowering agents eg fenofibrate non-dietary omega-3 fatty acids and niacin at least 8 weeks prior to the MRS at screening Patients were randomized to either mipomersen 200 mg or placebo for 13 weeks
Cohort F Patients with familial hypobetalipoproteinemia FHBL a documented APOB gene mutation that results in the expression of a truncated form of apo B Patients in this cohort were evaluated by MRS ultrasound and laboratory tests however they were not treated with mipomersen or placebo
Cohort G Patients with well-controlled type 2 diabetes mellitus HbA1c 80 hypercholesterolemia LDL-C 100 mgdL 259 mmolL and normal serum TG levels 200 mgdL 226 mmolL Patients were to have been on a stable dose of antidiabetic and lipid-lowering medications 3 months prior to screening and were expected to remain stable for the duration of the study Patients were randomized to either mipomersen 200 mg or placebo for 26 weeks followed by 26 additional weeks of mipomersen 200 mg Recruiting difficulties caused this cohort to close early
The original study design included 4 cohorts Cohorts A through D Subsequent protocol amendments added 3 cohorts Cohorts E F and G to the study truncated the enrollment of Cohort D and eliminated Cohorts B and C The study consisted of up to a 3-week screening period a 4-week Cohorts A and D 13-week Cohort E or 52-week Cohort G treatment period and a 20-week post-treatment follow-up period Cohort F was an observational cohort and therefore was not treated with study drug Patients in this cohort underwent a 15-week Magnetic resonance spectroscopy MRS and ultrasound evaluation period
The study cohorts are
Cohort A Healthy volunteers with LDL-C 140 mgdL 36 mmolL serum TG 200 mgdL 23 mmolL hemoglobin A1c HbA1c 60 and hepatic TG content 5 as measured by MRS at screening Patients were randomized to mipomersen 200 mg or placebo and treated for 4 weeks
Cohorts BC were eliminated in a protocol amendment prior to enrolling any patients and are not discussed further
Cohort D In an amendment to the protocol Cohort D was closed to enrollment One patient had already been enrolled in the study prior to the amendment The patient enrolled in this cohort had impaired fasting glucose defined as fasting blood glucose 6 mmolL and 7 mmolL and mixed dyslipidemia LDL-C 215 mgdL 56 mmolL and serum TG 200 mgdL 23 mmolL The patient was treated with mipomersen 200 mg for 4 weeks
Cohort E Patients with uncomplicated heterozygous familial hypercholesterolemia HeFH Alanine aminotransferase ALT 15 upper limit of normal Upper limit of normal ULN no evidence of insulin resistance or metabolic syndrome and hepatic TG content 5 by MRS at screening Patients were to remain on their baseline statin ezetimibe regimen but were to wash out from other lipid-lowering agents eg fenofibrate non-dietary omega-3 fatty acids and niacin at least 8 weeks prior to the MRS at screening Patients were randomized to either mipomersen 200 mg or placebo for 13 weeks
Cohort F Patients with familial hypobetalipoproteinemia FHBL a documented APOB gene mutation that results in the expression of a truncated form of apo B Patients in this cohort were evaluated by MRS ultrasound and laboratory tests however they were not treated with mipomersen or placebo
Cohort G Patients with well-controlled type 2 diabetes mellitus HbA1c 80 hypercholesterolemia LDL-C 100 mgdL 259 mmolL and normal serum TG levels 200 mgdL 226 mmolL Patients were to have been on a stable dose of antidiabetic and lipid-lowering medications 3 months prior to screening and were expected to remain stable for the duration of the study Patients were randomized to either mipomersen 200 mg or placebo for 26 weeks followed by 26 additional weeks of mipomersen 200 mg Recruiting difficulties caused this cohort to close early
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2005-005783-90 | EUDRACT_NUMBER | None | None |