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

NCT ID: NCT00694109

Last Updated: 2016-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2014-09-30

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.

Detailed Description

All familial hypercholesterolemia (FH) or severe hypercholesterolemia participants who had tolerated the treatment regimen in Protocol 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849) or MIPO3500108 (NCT00794664) and satisfactorily completed the study through to Week 28 were eligible for participation in this open label treatment extension study for up to 4 years or until mipomersen was commercially available, whichever comes first. Consenting participants who had tolerated mipomersen and satisfactorily completed 301012-CS17 (NCT00477594) through Year 3 may also enroll for up to an additional 2 years of treatment in this study or until mipomersen was commercially available, whichever comes first. All participants, who entered the study, received 200 mg mipomersen (ISIS 301012) subcutaneously (s.c.) every week, including those who were randomized to placebo in their initial study. Participants who were originally enrolled in Protocol 301012-CS5 (NCT00607373) and weighed <50 kg received 160 mg every week. Dose adjustments (70 mg injections administered three times per week, on separate days) were allowed for participants who were not tolerating or who had previous issues with tolerating the once a week injections due to injection site reactions (ISRs) or flu-like symptoms. Study visits and clinical lab assessments including hematology with differential, chemistry, serum lipid panel (total cholesterol, LDL-C, very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), apoA-1, triglycerides (TG) and Lp(a), and urinalysis was to be performed every 4-10 weeks during the treatment period. Plasma trough mipomersen (ISIS 301012) levels was to be measured to estimate exposure. Participants who completed dosing or who discontinued prematurely from the study for any reason was followed for safety for 24 weeks (safety follow-up period) after their last dose of mipomersen (ISIS 301012) or longer in the case of a significant adverse events (AE) or abnormal biochemical or clinical finding. Participants were required to return to the study center for clinical evaluation and clinical laboratory tests every 8 weeks during the safety follow-up period.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mipomersen

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

Group Type: EXPERIMENTAL

Mipomersen Sodium

Intervention Type: DRUG

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

Interventions

Mipomersen Sodium

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

Intervention Type: DRUG

Other Intervention Names

ISIS 301012; Kynamro®

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Kastle Therapeutics, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

Mission Viejo, California, United States

Newport Beach, California, United States

Bridgeport, Connecticut, United States

Melbourne, Florida, United States

Winter Park, Florida, United States

Chicago, Illinois, United States

Kansas City, Kansas, United States

Biddeford, Maine, United States

Boston, Massachusetts, United States

St Louis, Missouri, United States

Concord, New Hampshire, United States

New York, New York, United States

Charlotte, North Carolina, United States

Durham, North Carolina, United States

Cincinnati, Ohio, United States

Franklin, Ohio, United States

Portland, Oregon, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

Seattle, Washington, United States

São Paulo, São Paulo, Brazil

Winnipeg, Manitoba, Canada

London, Ontario, Canada

Chicoutimi, Quebec, Canada

Montreal, Quebec, Canada

Montreal, Quebec, Canada

Québec, Quebec, Canada

Sherbrooke, Quebec, Canada

Singapore, , Singapore

Observatory, South Africa, South Africa

Parktown, South Africa, South Africa

Taipei, Taiwan, Taiwan

London, United Kingdom, United Kingdom

Countries

United States; Brazil; Canada; Singapore; South Africa; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 27578134 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24366918 (View on PubMed)

Other Identifiers

2005-003450-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

301012-CS6

Identifier Type: -

Identifier Source: org_study_id