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 (FOCUS FH)

March 13, 2019 updated by: Kastle Therapeutics, LLC

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

309

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad Autonoma de Buenos Aires, Argentina
      • Cordoba, Argentina
  • Australia
      • Perth, Australia
      • South Brisbane, Australia
  • Belgium
      • Edegem, Belgium
      • Haine St. Paul, Belgium
      • Leuven, Belgium
  • Brazil
      • Rio de Janeiro, Brazil
      • Sao Paulo, Brazil
  • Canada
    • Quebec
      • Chicoutimi, Quebec, Canada
      • Montreal, Quebec, Canada
      • Sainte-Foy, Quebec, Canada
  • Croatia
      • Osijek, Croatia
      • Zagreb, Croatia
  • Czechia
      • Hradec Kralove, Czechia
      • Praha 1, Czechia
  • Denmark
      • Aarhus, Denmark
      • Viborg, Denmark
  • Germany
      • Aachen, Germany
      • Berlin, Germany
      • Freiburg, Germany
      • Hamburg, Germany
      • Heidelberg, Germany
      • Koeln, Germany
      • Magdeburg, Germany
  • Greece
      • Ioannina, Greece
      • Kallithea, Greece
  • Hong Kong
      • Hong Kong, Hong Kong
  • Hungary
      • Baja, Hungary
      • Budapest, Hungary
      • Debrecen, Hungary
  • India
      • New Delhi, India
  • Israel
      • Holon, Israel
      • Kfar Saba, Israel
      • Ofakim, Israel
  • Italy
      • Bologna, Italy
      • Napoli, Italy
      • Padova, Italy
      • Palermo, Italy
      • Pisa, Italy
      • Roma, Italy
  • Korea, Republic of
      • Seoul, Korea, Republic of
  • Malaysia
      • Kuala Lumpur, Malaysia
      • Kubang Kerian, Malaysia
  • Netherlands
      • Alkmaar, Netherlands
      • Amsterdam, Netherlands
      • Maastricht, Netherlands
      • Nijmegen, Netherlands
      • Utrecht, Netherlands
      • Waalwijk, Netherlands
  • New Zealand
      • Christchurch, New Zealand
  • Norway
      • Bodo, Norway
      • Oslo, Norway
      • Sandefjord, Norway
  • Poland
      • Bialystok, Poland
      • Gdansk, Poland
      • Katowice, Poland
      • Krakow, Poland
      • Naleczow, Poland
      • Poznan, Poland
      • Sopot, Poland
      • Szczecin, Poland
      • Warszawa, Poland
      • Wroclaw, Poland
  • Russian Federation
      • Barnaul, Russian Federation
      • Kemerovo, Russian Federation
      • Moscow, Russian Federation
      • Novosibirsk, Russian Federation
      • Petrozavodsk, Russian Federation
      • Ryazan, Russian Federation
      • Saint Petersburg, Russian Federation
      • St-Petersburg, Russian Federation
      • St. Petersburg, Russian Federation
      • Tomsk, Russian Federation
      • Yaroslavl, Russian Federation
  • South Africa
      • Cape Town, South Africa
      • Pretoria, South Africa
  • Spain
      • Madrid, Spain
  • Sweden
      • Stockholm, Sweden
  • Taiwan
      • New Taipei City, Taiwan
      • Taipei, Taiwan
  • Turkey
      • Ankara, Turkey
      • Istanbul, Turkey
      • Izmir, Turkey
      • Sivas, Turkey
  • Ukraine
      • Ivano-Frankivsk, Ukraine
      • Kiev, Ukraine
      • Kyiv, Ukraine
      • Odesa, Ukraine
      • Odessa, Ukraine
  • United Kingdom
      • Birmingham, United Kingdom
      • Cardiff, United Kingdom
      • Liverpool, United Kingdom
      • London, United Kingdom
      • Manchester, United Kingdom
      • Oldham, United Kingdom
  • United States
    • California
      • Mission Viejo, California, United States
    • Colorado
      • Aurora, Colorado, United States
    • Florida
      • Cooper City, Florida, United States
      • Winter Park, Florida, United States
    • Indiana
      • Indianapolis, Indiana, United States
    • Kansas
      • Kansas City, Kansas, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Michigan
      • Ann Arbor, Michigan, United States
      • Grandville, Michigan, United States
    • Minnesota
      • Rochester, Minnesota, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • New Jersey
      • Summit, New Jersey, United States
    • New York
      • North Massapequa, New York, United States
    • Oregon
      • Portland, Oregon, United States
    • Pennsylvania
      • Lancaster, Pennsylvania, United States
    • South Carolina
      • Charleston, South Carolina, United States
    • Tennessee
      • Nashville, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
    • Virginia
      • Norfolk, Virginia, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Regimen A: Mipomersen
Subcutaneous injection of mipomersen 200 mg once weekly
Drug: mipomersen sodium 200 mg
Subcutaneous mipomersen 200 mg once weekly
Other Names:
  • Kynamro (ISIS 301012)
Placebo Comparator: Regimen A: Placebo
Placebo matching subcutaneous injection once weekly.
Drug: Placebo
Placebo vehicle for subcutaneous injection.
Experimental: Regimen B: Mipomersen
Subcutaneous injection of mipomersen 70 mg thrice weekly.
Drug: mipomersen sodium 70 mg
Subcutaneous mipomersen 70 mg thrice weekly
Other Names:
  • Kynamro (ISIS 301012)
Placebo Comparator: Regimen B: Placebo
Placebo matching subcutaneous injection thrice weekly.
Drug: Placebo
Placebo vehicle for subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1
Time Frame: Baseline and Week 61
The percent change from baseline to PET in LDL-C was measured in Cohort 1, which included participants with severe heterozygous familial hypercholesterolemia (HeFH). Severe HeFH was defined as LDL-C levels ≥200 mg/deciliter (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.
Baseline and Week 61

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline To PET In LDL-C In Cohort 2
Time Frame: Baseline, PET (up to 60 weeks)
The percent change from baseline to PET in LDL-C was measured in Cohort 2, which included participants with HeFH with LDL-C levels ≥160 mg/dL and <200 mg/dL, plus the presence of CHD/risk equivalents.
Baseline, PET (up to 60 weeks)
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 1
Time Frame: Baseline and Week 61
The percent change from baseline to PET in Apo B was measured in participants in Cohort 1 with HeFH during the Blinded Treatment Period.
Baseline and Week 61
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 2
Time Frame: Baseline and Week 61
The percent change from baseline to PET in Apo B was measured in participants in Cohort 2 with HeFH during the Blinded Treatment Period.
Baseline and Week 61
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 1
Time Frame: Baseline and Week 61
The percent change from baseline to PET in Lipoprotein A1 was measured in participants in Cohort 1 with HeFH during the Blinded Treatment Period.
Baseline and Week 61
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 2
Time Frame: Baseline and Week 61
The percent change from baseline to PET in Lipoprotein A1 was measured in participants in Cohort 2 with HeFH during the Blinded Treatment Period.
Baseline and Week 61

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kastle Therapeutics, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2011

Primary Completion (Actual)

December 29, 2015

Study Completion (Actual)

December 29, 2015

Study Registration Dates

First Submitted

November 17, 2011

First Submitted That Met QC Criteria

November 17, 2011

First Posted (Estimate)

November 21, 2011

Study Record Updates

Last Update Posted (Actual)

March 26, 2019

Last Update Submitted That Met QC Criteria

March 13, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MIPO3801011
  • 2011-001480-42 (EudraCT Number)
  • EFC12875 (Other Identifier: Sanofi)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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