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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01475825




Registration number
NCT01475825
Ethics application status
Date submitted
17/11/2011
Date registered
21/11/2011
Date last updated
26/03/2019

Titles & IDs
Public title
A Study of the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients With Familial Hypercholesterolemia and Inadequately Controlled Low-Density Lipoprotein Cholesterol
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Followed by an Open-Label Continuation Period to Assess the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients With Familial Hypercholesterolemia and Inadequately Controlled Low-Density Lipoprotein Cholesterol
Secondary ID [1] 0 0
2011-001480-42
Secondary ID [2] 0 0
MIPO3801011
Universal Trial Number (UTN)
Trial acronym
FOCUS FH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolemia 0 0
Heterozygous Familial 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - mipomersen sodium 200 mg
Treatment: Drugs - Placebo
Treatment: Drugs - mipomersen sodium 70 mg

Experimental: Regimen A: Mipomersen - Subcutaneous injection of mipomersen 200 mg once weekly

Placebo comparator: Regimen A: Placebo - Placebo matching subcutaneous injection once weekly.

Experimental: Regimen B: Mipomersen - Subcutaneous injection of mipomersen 70 mg thrice weekly.

Placebo comparator: Regimen B: Placebo - Placebo matching subcutaneous injection thrice weekly.


Treatment: Drugs: mipomersen sodium 200 mg
Subcutaneous mipomersen 200 mg once weekly

Treatment: Drugs: Placebo
Placebo vehicle for subcutaneous injection.

Treatment: Drugs: mipomersen sodium 70 mg
Subcutaneous mipomersen 70 mg thrice weekly
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1
Timepoint [1] 0 0
Baseline and Week 61
Secondary outcome [1] 0 0
Percent Change From Baseline To PET In LDL-C In Cohort 2
Timepoint [1] 0 0
Baseline, PET (up to 60 weeks)
Secondary outcome [2] 0 0
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 1
Timepoint [2] 0 0
Baseline and Week 61
Secondary outcome [3] 0 0
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 2
Timepoint [3] 0 0
Baseline and Week 61
Secondary outcome [4] 0 0
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 1
Timepoint [4] 0 0
Baseline and Week 61
Secondary outcome [5] 0 0
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 2
Timepoint [5] 0 0
Baseline and Week 61

Eligibility
Key inclusion criteria
* Diagnosis of severe hypercholesterolemia (LDL-C =300 mg/dL (7.77 mmol/L) or LDL-C =200 mg/dL (5.18 mmol/L) with documented coronary heart disease (CHD) or CHD risk equivalents, or diagnosis of Heterozygous Familial Hypercholesterolemia and LDL-C =160 mg/dL (4.14 mmol/L) and <200 mg/dL (5.18 mmol/L))
* On stable, maximally tolerated, statin therapy for at least 12 weeks or if statin intolerant, on at least 1 medication from another class of hypolipidemic agents (i.e., bile acid sequestrants, niacin/nicotinic acid, cholesterol absorption inhibitors, fibrates).
* On stable, low fat diet for 12 weeks
* Body mass index (BMI) =40 kg/m2 and stable weight for > 6 weeks
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Significant health problems in the recent past including heart attack, stroke, coronary syndrome, unstable angina, heart failure, significant arrhythmia, hypertension, blood disorders, liver disease, cancer, digestive disorders, Type I diabetes, or uncontrolled Type II diabetes
* Apheresis within 3 months prior to Screening or expected to start apheresis during the treatment phase

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/12/2015
Sample size
Target
Accrual to date
Final
309
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Perth
Recruitment hospital [2] 0 0
- South Brisbane
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- Perth
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- South Brisbane
Recruitment outside Australia
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United States of America
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California
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Cordoba
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Edegem
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South Africa
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Pretoria
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Stockholm
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Istanbul
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Izmir
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Sivas
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Ukraine
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Kiev
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Cardiff
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Liverpool
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London
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Manchester
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Oldham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kastle Therapeutics, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Primary objective:

Determine whether mipomersen (ISIS 301012) significantly reduces atherogenic lipid levels in patients with severe heterozygous familial hypercholesterolemia (severe HeFH), defined as low-density lipoprotein cholesterol (LDL-C) levels =200 mg/dL plus the presence of coronary heart disease (CHD)/risk equivalents or LDL-C levels =300 mg/dL regardless of the presence of CHD/risk equivalents (referred to as Cohort 1) compared to placebo. Two different mipomersen dosing regimens will be studied: subcutaneous (SC) mipomersen 200 mg once weekly versus placebo, and SC mipomersen 70 mg thrice weekly versus placebo.

Secondary Objectives:

* Determine whether there are qualitative differences between the safety profiles of the 2 dosing regimens and placebo in Cohort 1, patients with HeFH with LDL-C levels =160 mg/dL and \<200 mg/dL plus the presence of CHD/risk equivalents (referred to as Cohort 2), and the overall study population
* Determine whether there are qualitative differences between the tolerability of the 2 dosing regimens and placebo in Cohort 1, Cohort 2, and the overall study population
* Further characterize the pharmacokinetics (PK) of the 2 dosing regimens in Cohort 1, Cohort 2, and the overall study population
* Determine whether the 2 mipomersen dosing regimens significantly reduce atherogenic lipid levels in Cohort 2 compared to placebo
* Obtain additional data regarding ongoing safety and efficacy of mipomersen in patients with FH and inadequately controlled LDL-C who complete the primary efficacy assessment visit (PET) in the Blinded Treatment Period and continue treatment in Open-Label Continuation Period
Trial website
https://clinicaltrials.gov/study/NCT01475825
Trial related presentations / publications
Tragante V, Asselbergs FW, Swerdlow DI, Palmer TM, Moore JH, de Bakker PIW, Keating BJ, Holmes MV. Harnessing publicly available genetic data to prioritize lipid modifying therapeutic targets for prevention of coronary heart disease based on dysglycemic risk. Hum Genet. 2016 May;135(5):453-467. doi: 10.1007/s00439-016-1647-9. Epub 2016 Mar 5.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Genzyme, a Sanofi Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01475825