Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia

This study has been completed.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00477594
First received: May 22, 2007
Last updated: December 2, 2013
Last verified: December 2013
Results First Received: February 25, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
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
Intervention: Drug: mipomersen sodium

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients who completed dosing in study 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008) at a site in the U.S. with an acceptable safety profile, per Investigator judgment, were eligible to enroll in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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). Patients who participated in study 301012-CS8 or Cohort D of study 301012-CS9 received 200 mg mipomersen QW.

Reporting Groups
  Description
Mipomersen 200 mg Per Week Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years.
Mipomersen 200 mg Every Other Week 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.

Participant Flow for 3 periods

Period 1:   Year 1 and Year 2
    Mipomersen 200 mg Per Week     Mipomersen 200 mg Every Other Week  
STARTED     16     5  
COMPLETED     7     1  
NOT COMPLETED     9     4  
Adverse Event                 4                 2  
Physician Decision                 2                 1  
Withdrawal by Subject                 2                 1  
Other                 1                 0  

Period 2:   Year 3
    Mipomersen 200 mg Per Week     Mipomersen 200 mg Every Other Week  
STARTED     4     0  
COMPLETED     2     0  
NOT COMPLETED     2     0  
Adverse Event                 1                 0  
Withdrawal by Subject                 1                 0  

Period 3:   Follow-up Period
    Mipomersen 200 mg Per Week     Mipomersen 200 mg Every Other Week  
STARTED     16     5  
COMPLETED     13     4  
NOT COMPLETED     3     1  
Withdrawal by Subject                 2                 1  
Other                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Mipomersen 200 mg Per Week Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years.
Mipomersen 200 mg Every Other Week 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.
Total Total of all reporting groups

Baseline Measures
    Mipomersen 200 mg Per Week     Mipomersen 200 mg Every Other Week     Total  
Number of Participants  
[units: participants]
  16     5     21  
Age  
[units: years]
Mean ± Standard Deviation
  47.1  ± 11.6     54.6  ± 15.7     48.9  ± 12.7  
Gender  
[units: participants]
     
Female     4     2     6  
Male     12     3     15  
Race/Ethnicity, Customized  
[units: participants]
     
Hispanic or Latino     1     0     1  
Not Hispanic or Latino     15     5     20  
Race/Ethnicity, Customized  
[units: participants]
     
White     14     5     19  
Other race     1     0     1  
Multiple     1     0     1  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  28.9  ± 5.60     27.4  ± 4.81     28.6  ± 5.34  
Metabolic syndrome [1]
[units: participants]
     
No     8     3     11  
Yes     8     2     10  
Tobacco Use  
[units: participants]
     
Current     1     0     1  
Non-current     5     2     7  
Never     10     3     13  
Alcohol use  
[units: participants]
     
Current     13     3     16  
Non-current     1     0     1  
Never     2     2     4  
[1]

A patient was classified as having metabolic syndrome if any 3 of the following risk factors existed: 1) Waist circumference ≥102 cm (men) or ≥88 cm (women); 2) Triglycerides ≥150 mg/dL*; 3) High density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women)*; 4) Systolic blood pressure ≥130 or diastolic ≥85 mmHg*; 5) Fasting glucose ≥100 mg/dL*.

* = or on medication for the specified risk factor.




  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)   [ Time Frame: Baseline and Weeks 52 and 104 ]

2.  Primary:   Low-density Lipoprotein Cholesterol (LDL-C) Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]

3.  Secondary:   Percent Change From Baseline in Apolipoprotein B   [ Time Frame: Baseline and Weeks 52 and 104 ]

4.  Secondary:   Apolipoprotein B Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]

5.  Secondary:   Percent Change From Baseline in Total Cholesterol   [ Time Frame: Baseline and Weeks 52 and 104. ]

6.  Secondary:   Total Cholesterol Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]

7.  Secondary:   Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol   [ Time Frame: Baseline and Weeks 52 and 104. ]

8.  Secondary:   Non-High-Density Lipoprotein Cholesterol Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]

9.  Secondary:   Number of Participants With Treatment-Emergent Adverse Events (AEs)   [ Time Frame: 2 years ]

10.  Secondary:   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. ]

11.  Secondary:   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 ]

12.  Secondary:   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. ]

13.  Secondary:   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. ]

14.  Secondary:   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. ]

15.  Other Pre-specified:   Percent Change From Baseline in Triglycerides   [ Time Frame: Baseline and Weeks 52 and 104. ]

16.  Other Pre-specified:   Triglycerides Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]

17.  Other Pre-specified:   Percent Change From Baseline in Lipoprotein(a)   [ Time Frame: Baseline and Weeks 52 and 104. ]

18.  Other Pre-specified:   Lipoprotein(a) Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]

19.  Other Pre-specified:   Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol   [ Time Frame: Baseline and Weeks 52 and 104. ]

20.  Other Pre-specified:   Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]

21.  Other Pre-specified:   Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol   [ Time Frame: Baseline and Weeks 52 and 104. ]

22.  Other Pre-specified:   Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]

23.  Other Pre-specified:   Percent Change From Baseline in Apolipoprotein A1   [ Time Frame: Baseline and Weeks 52 and 104. ]

24.  Other Pre-specified:   Apolipoprotein A1 Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]

25.  Other Pre-specified:   Percent Change From Baseline in High-Density Lipoprotein Cholesterol   [ Time Frame: Baseline and Weeks 52 and 104. ]

26.  Other Pre-specified:   High-Density Lipoprotein Cholesterol Over Time   [ Time Frame: Baseline and Weeks 52 and 104. ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Genzyme Medical Information
Organization: Genzyme Corporation
phone: 617-252-7832


No publications provided by Sanofi

Publications automatically indexed to this study:

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00477594     History of Changes
Other Study ID Numbers: 301012-CS17, 2007-001024-12
Study First Received: May 22, 2007
Results First Received: February 25, 2013
Last Updated: December 2, 2013
Health Authority: United States: Food and Drug Administration