Lipid Metabolism, Inborn ErrorsPhase 2NCT00477594
Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
A Phase 2 study testing mipomersen sodium in people with Lipid Metabolism, Inborn Errors and Hypercholesterolemia, Autosomal Dominant, run by Kastle Therapeutics, LLC at 5 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of extended dosing of mipomersen in patients with familial hypercholesterolemia on lipid-lowering therapy who have completed either the 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008) clinical drug trials. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Lipid Metabolism, Inborn Errors, Hypercholesterolemia, Autosomal Dominant, Hyperlipidemias
- What is being tested?
- mipomersen sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 5 sitesUnited States
- Study dates
- May 2007to Jul 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Satisfactory completion of dosing and Week 7 or Week 15 assessments (depending on the treatment and dose received) in their initial study (Protocol 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008)).
Who cannot join
- Have a new condition or worsening of existing condition which in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with patient's participation in or completion of the study.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Study site
Auburn, Maine, 04210
Study site
Biddeford, Maine, 04005
Study site
Chicago, Illinois, 60654
Study site
Cincinnati, Ohio, 45212
Study site
Scarborough, Maine, 04074
About this study
Official title: An Open-Label Extension Study to Assess the Long-term Safety and Efficacy of Mipomersen in Subjects With Familial Hypercholesterolemia
The purpose of this study is to evaluate the safety and efficacy of extended dosing of mipomersen in patients with familial hypercholesterolemia on lipid-lowering therapy who have completed either the 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008) clinical drug trials.
Read the detailed description
Familial Hypercholesterolemia (FH) is an autosomal dominant metabolic disorder characterized by markedly elevated low density lipoprotein (LDL), premature onset of atherosclerosis, and development of xanthomata. There are two distinct subpopulations that have a high unmet medical need due to the lack of alternative therapy: homozygotes, who have two defective LDL receptor (LDL-R) genes, and heterozygotes with a history of cardiovascular disease (CVD) on maximally tolerated therapy. Treatment for FH is directed at lowering plasma levels of LDL-C.
Mipomersen is an antisense drug targeted to human apolipoprotein B (apoB), the principal apolipoprotein of atherogenic LDL-C and its metabolic precursor, very low density lipoprotein (VLDL). Mipomersen is complimentary to the coding region of the messenger ribonucleic acid (mRNA) for apo-B. Inhibition of apo-B would be expected to impair VLDL synthesis and result in lowered levels of LDL-C.
In early clinical trials, mipomersen has been shown to reduce levels of LDL-C to recommended target levels in some participants.
This was an open-label extension study, which consisted of a ≤2-week screening period, up to 3 years of treatment with mipomersen, and a 24-week post-treatment follow-up period. Patients who participated in Cohorts A, B, or C in study 301012-CS9 were randomized in a 1:1 ratio to mipomersen 200 mg once a week (QW) or 200 mg mipomersen every other week (QOW) for up to 3 years. Patients randomized to mipomersen 200 mg QOW were allowed to receive mipomersen 200 mg QW at the Investigator's discretion after the first 52 weeks of the treatment period. Patients who participated in study 301012-CS8 or Cohort D of study 301012-CS9 received 200 mg mipomersen QW for up to 3 years.
- Conditions
- Lipid Metabolism, Inborn Errors, Hypercholesterolemia, Autosomal Dominant, Hyperlipidemias, Metabolic Diseases, Hyperlipoproteinemia Type II, Metabolism, Inborn Errors
- Being tested
- mipomersen sodium
- Keywords
- Familial Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia, Homozygous Familial Hypercholesterolemia, ISIS 301012, mipomersen, Open Label Extension
- Medical subject headings
- Lipid Metabolism, Inborn Errors, Hyperlipoproteinemia Type II, Hyperlipidemias, Metabolic Diseases, Metabolism, Inborn Errors, Genetic Diseases, Inborn, Infant, Newborn, Diseases, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mipomersen sodiumDrug
Also called ISIS 301012, Kynamro™
200 mg/ml, in 1 ml solution for subcutaneous injection.
| Study group | Role | What they receive |
|---|---|---|
| Mipomersen 200 mg per week | Experimental | Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years. Receives: Drug: mipomersen sodium |
| Mipomersen 200 mg every other week | Experimental | Participants received 200 mg mipomersen every other week by subcutaneous injection, for up to 3 years. Participants could receive mipomersen 200 mg once a week at the Investigator's discretion after the first 52 weeks of the treatment period. Receives: Drug: mipomersen sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides <400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Measured: Baseline and Weeks 52 and 104
Low-density Lipoprotein Cholesterol (LDL-C) Over Time
Samples were taken following an overnight fast. For patients with triglycerides <400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Measured: Baseline and Weeks 52 and 104.
Secondary outcomes (12)
Percent Change From Baseline in Apolipoprotein B
Apolipoprotein B was measured in mg/dL. Samples were taken following an overnight fast. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Measured: Baseline and Weeks 52 and 104
Apolipoprotein B Over Time
For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Measured: Baseline and Weeks 52 and 104.
Percent Change From Baseline in Total Cholesterol
Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
Measured: Baseline and Weeks 52 and 104.
Total Cholesterol Over Time
For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Measured: Baseline and Weeks 52 and 104.
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol
Non-high-density lipoprotein cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
Measured: Baseline and Weeks 52 and 104.
Non-High-Density Lipoprotein Cholesterol Over Time
For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Measured: Baseline and Weeks 52 and 104.
Number of Participants With Treatment-Emergent Adverse Events (AEs)
AEs were considered as related if assessed by the Investigator as possibly, probably or definitely related to study drug. The severity of each event was assessed using the following categories: Mild (symptom(s) barely noticeable to the patient or do not make the patient uncomfortable); Moderate (symptom(s) of a sufficient severity to make the patient uncomfortable, performance of daily activities is influenced) or Severe (symptom(s) of a sufficient severity to cause the patient severe discomfort, may cause cessation of treatment with the study drug). Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.
Measured: 2 years
Percent Change From Baseline in Clinical Chemistry Parameters
Measured: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Percent Change From Baseline in Hematology Parameters
Measured: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment
Percent Change From Baseline in Blood Pressure
Measured: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Percent Change From Baseline in Pulse Rate
Measured: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Percent Change From Baseline in Respiratory Rate
Measured: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2007 (estimated)
- Study startMay 2007
- Primary completionMar 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lipid Metabolism, Inborn ErrorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kastle Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00477594
- Sponsor's protocol ID
- 301012-CS17
- Other IDs
- 2007-001024-12
- Status last verified
- Aug 2016
- First submitted
- 22 May 2007
- Last updated
- 9 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Patel N, Hegele RA. Mipomersen as a potential adjunctive therapy for hypercholesterolemia. Expert Opin Pharmacother. 2010 Oct;11(15):2569-72. doi: 10.1517/14656566.2010.512006.
PubMed 20707601
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension Study to Assess the Long-term Safety and Efficacy of Mipomersen in Subjects With Familial Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT00477594
- Acronym / sponsor ID
- 301012-CS17
- Conditions
- Lipid Metabolism, Inborn Errors, Hypercholesterolemia, Autosomal Dominant, Hyperlipidemias, Metabolic Diseases, Hyperlipoproteinemia Type II, Metabolism, Inborn Errors
- Keywords
- Familial Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia, Homozygous Familial Hypercholesterolemia, ISIS 301012, mipomersen, Open Label Extension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Kastle Therapeutics, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Study start
- May 2007
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 24 May 2007 (estimated)
- Results
- Posted 5 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and efficacy of extended dosing of mipomersen in patients with familial hypercholesterolemia on lipid-lowering therapy who have completed either the 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008) clinical drug trials.
Detailed description
Familial Hypercholesterolemia (FH) is an autosomal dominant metabolic disorder characterized by markedly elevated low density lipoprotein (LDL), premature onset of atherosclerosis, and development of xanthomata. There are two distinct subpopulations that have a high unmet medical need due to the lack of alternative therapy: homozygotes, who have two defective LDL receptor (LDL-R) genes, and heterozygotes with a history of cardiovascular disease (CVD) on maximally tolerated therapy. Treatment for FH is directed at lowering plasma levels of LDL-C.
Mipomersen is an antisense drug targeted to human apolipoprotein B (apoB), the principal apolipoprotein of atherogenic LDL-C and its metabolic precursor, very low density lipoprotein (VLDL). Mipomersen is complimentary to the coding region of the messenger ribonucleic acid (mRNA) for apo-B. Inhibition of apo-B would be expected to impair VLDL synthesis and result in lowered levels of LDL-C.
In early clinical trials, mipomersen has been shown to reduce levels of LDL-C to recommended target levels in some participants.
This was an open-label extension study, which consisted of a ≤2-week screening period, up to 3 years of treatment with mipomersen, and a 24-week post-treatment follow-up period. Patients who participated in Cohorts A, B, or C in study 301012-CS9 were randomized in a 1:1 ratio to mipomersen 200 mg once a week (QW) or 200 mg mipomersen every other week (QOW) for up to 3 years. Patients randomized to mipomersen 200 mg QOW were allowed to receive mipomersen 200 mg QW at the Investigator's discretion after the first 52 weeks of the treatment period. Patients who participated in study 301012-CS8 or Cohort D of study 301012-CS9 received 200 mg mipomersen QW for up to 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mipomersen 200 mg per week | Experimental | Drug: mipomersen sodiumParticipants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years. |
| Mipomersen 200 mg every other week | Experimental | Drug: mipomersen sodiumParticipants received 200 mg mipomersen every other week by subcutaneous injection, for up to 3 years. Participants could receive mipomersen 200 mg once a week at the Investigator's discretion after the first 52 weeks of the treatment period. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Satisfactory completion of dosing and Week 7 or Week 15 assessments (depending on the treatment and dose received) in their initial study (Protocol 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008)).
Key exclusion criteria (1 listed)
- Have a new condition or worsening of existing condition which in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with patient's participation in or completion of the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mipomersen sodiumAlso: ISIS 301012, Kynamro™200 mg/ml, in 1 ml solution for subcutaneous injection. | Drug | Mipomersen 200 mg every other week, Mipomersen 200 mg per week |
Primary outcome
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
Time frame: Baseline and Weeks 52 and 104
LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides <400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Low-density Lipoprotein Cholesterol (LDL-C) Over Time
Time frame: Baseline and Weeks 52 and 104.
Samples were taken following an overnight fast. For patients with triglycerides <400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
12 secondary outcomes
Percent Change From Baseline in Apolipoprotein B
Time frame: Baseline and Weeks 52 and 104
Apolipoprotein B Over Time
Time frame: Baseline and Weeks 52 and 104.
Percent Change From Baseline in Total Cholesterol
Time frame: Baseline and Weeks 52 and 104.
Total Cholesterol Over Time
Time frame: Baseline and Weeks 52 and 104.
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol
Time frame: Baseline and Weeks 52 and 104.
Non-High-Density Lipoprotein Cholesterol Over Time
Time frame: Baseline and Weeks 52 and 104.
Number of Participants With Treatment-Emergent Adverse Events (AEs)
Time frame: 2 years
Percent Change From Baseline in Clinical Chemistry Parameters
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Percent Change From Baseline in Hematology Parameters
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment
Percent Change From Baseline in Blood Pressure
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Percent Change From Baseline in Pulse Rate
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Percent Change From Baseline in Respiratory Rate
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20707601Patel N, Hegele RA. Mipomersen as a potential adjunctive therapy for hypercholesterolemia. Expert Opin Pharmacother. 2010 Oct;11(15):2569-72. doi: 10.1517/14656566.2010.512006.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Genzyme, a Sanofi Company
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing mipomersen sodium in people with Lipid Metabolism, Inborn Errors and Hypercholesterolemia, Autosomal Dominant, run by Kastle Therapeutics, LLC at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Apr 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) (time frame: Baseline and Weeks 52 and 104). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00477594, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2016.