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

NCT01475825 | Completed Phase 3 Results DMC

• 3 other identifiers: MIPO38010112011-001480-42EFC12875
• Study Type: interventional
• Target: 309
• Locations: 30 countries
• Sites: 113

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

Conditions

Hypercholesterolemia; Heterozygous Familial

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1

  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 Outcomes (5)

• Percent Change From Baseline To PET In LDL-C In Cohort 2

  Baseline, PET (up to 60 weeks)

• Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 1

  Baseline and Week 61

• Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 2

  Baseline and Week 61

• Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 1

  Baseline and Week 61

• Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 2

  Baseline and Week 61

Study Arms (4)

Regimen A: Mipomersen

EXPERIMENTAL

Subcutaneous injection of mipomersen 200 mg once weekly

Drug: mipomersen sodium 200 mg

Regimen A: Placebo

PLACEBO COMPARATOR

Placebo matching subcutaneous injection once weekly.

Drug: Placebo

Regimen B: Mipomersen

EXPERIMENTAL

Subcutaneous injection of mipomersen 70 mg thrice weekly.

Drug: mipomersen sodium 70 mg

Regimen B: Placebo

PLACEBO COMPARATOR

Placebo matching subcutaneous injection thrice weekly.

Drug: Placebo

Interventions

mipomersen sodium 200 mg DRUG

Subcutaneous mipomersen 200 mg once weekly

Also known as: Kynamro (ISIS 301012)

Regimen A: Mipomersen

Placebo DRUG

Placebo vehicle for subcutaneous injection.

Regimen A: Placebo; Regimen B: Placebo

mipomersen sodium 70 mg DRUG

Subcutaneous mipomersen 70 mg thrice weekly

Also known as: Kynamro (ISIS 301012)

Regimen B: Mipomersen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kastle Therapeutics, LLC: lead

Study Sites (113)

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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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Related Publications (1)

• 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.

  PMID: 26946290 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

mipomersen

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Medical Information
• Organization: Kastle Therapeutics, LLC

medinfo@genzyme.com

1-800-745-4447

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: November 21, 2011
• Study Start: December 1, 2011
• Primary Completion: December 29, 2015
• Study Completion: December 29, 2015
• Last Updated: March 26, 2019
• Results First Posted: March 14, 2019

Record last verified: 2019-03

Locations

IL (3); HK (1); KR (1); IT (6); UA (4); NZ (1); CZ (2); HU (3); DE (7); TU (4); BE (3); ZA (2); DK (2); PL (10); BR (2); SE (1); AR (2); CR (2); AU (2); ES (1); GR (2); TW (2); MY (2); NL (6); CA (3); US (20); RU (9); GB (6); IN (1); NO (3)