An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

NCT00694109 | Completed Phase 3 Results

• 2 other identifiers: 301012-CS62005-003450-10
• Study Type: interventional
• Target: 144
• Locations: 7 countries
• Sites: 33

Brief Summary

To evaluate the safety and efficacy of extended dosing with mipomersen (ISIS 301012) in participants with familial hypercholesterolemia or severe hypercholesterolemia on lipid-lowering therapy who had completed either the 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849), 301012-CS17 (NCT00477594) or MIPO3500108 (NCT00794664) clinical drug trials.

Conditions

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

Keywords

Familial Hypercholesterolemia; FH; Heterozygous Familial Hypercholesterolemia; HeFH; Homozygous Familial Hypercholesterolemia; HoFH

Outcome Measures

Primary Outcomes (4)

• Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)

  Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).

  Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

• Percent Change From Baseline in Apolipoprotein B (Apo B)

  Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).

  Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

• Percent Change From Baseline in Total Cholesterol

  Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).

  Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

• Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C)

  Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).

  Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Secondary Outcomes (17)

• Percent Change From Baseline in Triglycerides

  Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

• Percent Change From Baseline in Lipoprotein (a)

  Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

• Percent Change From Baseline in LDL Particles' Size (Total)

  Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

• Percent Change From Baseline in LDL Particles' Size (Large)

  Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

• Percent Change From Baseline in LDL Particles' Size (Medium)

  Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Study Arms (1)

Mipomersen

EXPERIMENTAL

Mipomersen Sodium once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.

Drug: Mipomersen Sodium

Interventions

Mipomersen Sodium DRUG

Subcutaneous injection as a single injection directly into the abdomen, thigh, or outer area of the upper arm.

Also known as: ISIS 301012, Kynamro®

Mipomersen

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Satisfactory completion of dosing in their initial study (Protocol 301012-CS5 \[NCT00607373\], 301012-CS7 \[NCT00706849\], 301012-CS17 \[NCT00477594\], or MIPO3500108 \[NCT00794664\])

You may not qualify if:

• Had any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study

Sponsors & Collaborators

• Kastle Therapeutics, LLC: lead
• Ionis Pharmaceuticals, Inc.: collaborator

Study Sites (33)

Unknown Facility

Mission Viejo, California, 92691, United States

Location

Unknown Facility

Newport Beach, California, 92660, United States

Location

Unknown Facility

Bridgeport, Connecticut, 06606, United States

Location

Unknown Facility

Melbourne, Florida, 32901, United States

Location

Unknown Facility

Winter Park, Florida, 32792, United States

Location

Unknown Facility

Chicago, Illinois, 60654, United States

Location

Unknown Facility

Kansas City, Kansas, 66160, United States

Location

Unknown Facility

Biddeford, Maine, 04005, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Concord, New Hampshire, 03301, United States

Location

Unknown Facility

New York, New York, 10032, United States

Location

Unknown Facility

Charlotte, North Carolina, 28204, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Cincinnati, Ohio, 45212, United States

Location

Unknown Facility

Franklin, Ohio, 45005, United States

Location

Unknown Facility

Portland, Oregon, 97239, United States

Location

Unknown Facility

Nashville, Tennessee, 37232, United States

Location

Unknown Facility

Dallas, Texas, 75226, United States

Location

Unknown Facility

Seattle, Washington, 98104, United States

Location

Unknown Facility

São Paulo, São Paulo, Brazil

Location

Unknown Facility

Winnipeg, Manitoba, R3A 1M5, Canada

Location

Unknown Facility

London, Ontario, N6A 5K8, Canada

Location

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Chicoutimi, Quebec, G7H 5H6, Canada

Location

Unknown Facility

Montreal, Quebec, H1T 1C8, Canada

Location

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Montreal, Quebec, H2W 1R7, Canada

Location

Unknown Facility

Québec, Quebec, G1V 4M6, Canada

Location

Unknown Facility

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Unknown Facility

Singapore, 168752, Singapore

Location

Unknown Facility

Observatory, South Africa, 7925, South Africa

Location

Unknown Facility

Parktown, South Africa, 2193, South Africa

Location

Unknown Facility

Taipei, Taiwan, 11217, Taiwan

Location

Unknown Facility

London, United Kingdom, WC1N 3BG, United Kingdom

Location

Related Publications (2)

• Duell PB, Santos RD, Kirwan BA, Witztum JL, Tsimikas S, Kastelein JJP. Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia. J Clin Lipidol. 2016 Jul-Aug;10(4):1011-1021. doi: 10.1016/j.jacl.2016.04.013. Epub 2016 May 9.

  PMID: 27578134 DERIVED

• Santos RD, Duell PB, East C, Guyton JR, Moriarty PM, Chin W, Mittleman RS. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J. 2015 Mar 1;36(9):566-75. doi: 10.1093/eurheartj/eht549. Epub 2013 Dec 23.

  PMID: 24366918 DERIVED

MeSH Terms

Conditions

Lipid Metabolism, Inborn Errors; Hyperlipoproteinemia Type II; Hyperlipidemias; Metabolic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders; Homozygous Familial Hypercholesterolemia

Interventions

mipomersen

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2008
• First Posted: June 10, 2008
• Study Start: April 1, 2008
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: September 9, 2016
• Results First Posted: December 21, 2015

Record last verified: 2016-08

Locations

SG (1); US (20); BR (1); GB (1); TW (1); CA (7); ZA (2)