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

NCT ID: NCT01475825

Last Updated: 2019-03-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

309 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2015-12-29

Brief Summary

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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

Detailed Description

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The study consisted of a Screening period of up to 4 weeks, Blinded Treatment Phase of 60 weeks, Open-Label Continuation Period of 26 weeks, and Post-Treatment Phase of 24 weeks.

Study Design, masking - Study treatment was blinded (double-blinded) through the Primary Efficacy Assessment Visit in the Blinded Treatment Period. Study treatment was open-label in the Open-Label Continuation Period.

Conditions

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Hypercholesterolemia Heterozygous Familial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Regimen A: Mipomersen

Subcutaneous injection of mipomersen 200 mg once weekly

Group Type EXPERIMENTAL

mipomersen sodium 200 mg

Intervention Type DRUG

Subcutaneous mipomersen 200 mg once weekly

Regimen A: Placebo

Placebo matching subcutaneous injection once weekly.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo vehicle for subcutaneous injection.

Regimen B: Mipomersen

Subcutaneous injection of mipomersen 70 mg thrice weekly.

Group Type EXPERIMENTAL

mipomersen sodium 70 mg

Intervention Type DRUG

Subcutaneous mipomersen 70 mg thrice weekly

Regimen B: Placebo

Placebo matching subcutaneous injection thrice weekly.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo vehicle for subcutaneous injection.

Interventions

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mipomersen sodium 200 mg

Subcutaneous mipomersen 200 mg once weekly

Intervention Type DRUG

Placebo

Placebo vehicle for subcutaneous injection.

Intervention Type DRUG

mipomersen sodium 70 mg

Subcutaneous mipomersen 70 mg thrice weekly

Intervention Type DRUG

Other Intervention Names

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Kynamro (ISIS 301012) Kynamro (ISIS 301012)

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kastle Therapeutics, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

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Mission Viejo, California, United States

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Aurora, Colorado, United States

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Cooper City, Florida, United States

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Winter Park, Florida, United States

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Indianapolis, Indiana, United States

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Kansas City, Kansas, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Grandville, Michigan, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Summit, New Jersey, United States

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North Massapequa, New York, United States

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Portland, Oregon, United States

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Lancaster, Pennsylvania, United States

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Charleston, South Carolina, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Norfolk, Virginia, United States

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Buenos Aires, , Argentina

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Córdoba, , Argentina

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Perth, , Australia

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South Brisbane, , Australia

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Edegem, , Belgium

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Haine-Saint-Paul, , Belgium

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Leuven, , Belgium

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Chicoutimi, Quebec, Canada

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Montreal, Quebec, Canada

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Sainte-Foy, Quebec, Canada

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Osijek, , Croatia

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Zagreb, , Croatia

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Hradec Králové, , Czechia

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Prague, , Czechia

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Aarhus, , Denmark

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Viborg, , Denmark

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Aachen, , Germany

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Berlin, , Germany

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Cologne, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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Heidelberg, , Germany

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Magdeburg, , Germany

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Ioannina, , Greece

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Kallithea, , Greece

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Hong Kong, , Hong Kong

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Baja, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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New Delhi, , India

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Holon, , Israel

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Kfar Saba, , Israel

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Ofakim, , Israel

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Bologna, , Italy

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Napoli, , Italy

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Padua, , Italy

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Palermo, , Italy

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Pisa, , Italy

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Roma, , Italy

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Kuala Lumpur, , Malaysia

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Kubang Kerian, , Malaysia

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Alkmaar, , Netherlands

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Amsterdam, , Netherlands

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Maastricht, , Netherlands

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Nijmegen, , Netherlands

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Utrecht, , Netherlands

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Waalwijk, , Netherlands

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Christchurch, , New Zealand

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Bodø, , Norway

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Oslo, , Norway

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Sandefjord, , Norway

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Bialystok, , Poland

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Gdansk, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Nałęczów, , Poland

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Poznan, , Poland

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Sopot, , Poland

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Szczecin, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Barnaul, , Russia

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Kemerovo, , Russia

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Moscow, , Russia

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Novosibirsk, , Russia

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Petrozavodsk, , Russia

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Ryazan, , Russia

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Saint Petersburg, , Russia

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Tomsk, , Russia

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Yaroslavl, , Russia

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Cape Town, , South Africa

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Pretoria, , South Africa

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Seoul, , South Korea

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Madrid, , Spain

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Stockholm, , Sweden

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New Taipei City, , Taiwan

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Taipei, , Taiwan

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Sivas, , Turkey (Türkiye)

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Ivano-Frankivsk, , Ukraine

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Kiev, , Ukraine

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Kyiv, , Ukraine

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Odesa, , Ukraine

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Birmingham, , United Kingdom

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Cardiff, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Oldham, , United Kingdom

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Countries

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United States Argentina Australia Belgium Brazil Canada Croatia Czechia Denmark Germany Greece Hong Kong Hungary India Israel Italy Malaysia Netherlands New Zealand Norway Poland Russia South Africa South Korea Spain Sweden Taiwan Turkey (Türkiye) Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 26946290 (View on PubMed)

Other Identifiers

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2011-001480-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC12875

Identifier Type: OTHER

Identifier Source: secondary_id

MIPO3801011

Identifier Type: -

Identifier Source: org_study_id

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