Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia (RADICHOL 1)

This study has been completed.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by (Responsible Party):
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00607373
First received: January 22, 2008
Last updated: May 30, 2013
Last verified: May 2013
Results First Received: February 15, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   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
Interventions: Drug: mipomersen
Drug: Placebo

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Sixty-one patients were screened and fifty-one randomized. Eligible patients were randomized in a 2:1 ratio to receive 200 mg mipomersen or matching volume placebo subcutaneous (SC) injections weekly.

Reporting Groups
  Description
Placebo Participants received placebo as a subcutaneous injection once a week for 26 weeks
Mipomersen Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Participant Flow for 2 periods

Period 1:   Treatment Period
    Placebo     Mipomersen  
STARTED     17     34  
COMPLETED     17 [1]   28 [2]
NOT COMPLETED     0     6  
Adverse Event                 0                 4  
Physician Decision                 0                 1  
Withdrawal by Subject                 0                 1  
[1] 16 enrolled in open-label extension study NCT00694109
[2] 23 enrolled in open-label extension study NCT00694109

Period 2:   Follow-up Period
    Placebo     Mipomersen  
STARTED     1 [1]   11 [1]
COMPLETED     0     6  
NOT COMPLETED     1     5  
Not specified                 0                 1  
Protocol Violation                 0                 1  
Withdrawal by Subject                 1                 3  
[1] Participants enrolled in the open-label extension (NCT00694109) or continued in the follow-up period



  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
Placebo Participants received placebo as a subcutaneous injection once a week for 26 weeks
Mipomersen Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo     Mipomersen     Total  
Number of Participants  
[units: participants]
  17     34     51  
Age  
[units: years]
Mean ± Standard Deviation
  33.0  ± 14.1     30.4  ± 11.5     31.3  ± 12.4  
Gender  
[units: participants]
     
Female     10     19     29  
Male     7     15     22  
Race/Ethnicity, Customized  
[units: participants]
     
Hispanic or Latino     1     5     6  
Not Hispanic or Latino     16     29     45  
Race/Ethnicity, Customized  
[units: participants]
     
White     13     25     38  
Asian     3     8     11  
Black     1     1     2  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation
  26.32  ± 4.41     25.97  ± 5.81     26.08  ± 5.34  
Waist/hip ratio  
[units: ratio]
Mean ± Standard Deviation
  0.83  ± 0.07     0.85  ± 0.06     0.84  ± 0.07  
Metabolic syndrome [1]
[units: participants]
     
No     16     27     43  
Yes     1     7     8  
Tobacco Use  
[units: participants]
     
Current     3     7     10  
Non-current     3     4     7  
Never     11     23     34  
Alcohol Use  
[units: participants]
     
Current     6     14     20  
Non-current     3     3     6  
Never     8     17     25  
Fasting serum insulin  
[units: microIU/mL]
Mean ± Standard Deviation
  9.72  ± 5.98     11.54  ± 14.78     10.93  ± 12.51  
Fasting hemoglobin A1c  
[units: percentage of total hemoglobin]
Mean ± Standard Deviation
  5.47  ± 0.22     5.34  ± 0.37     5.38  ± 0.33  
Weight [2]
[units: participants]
     
<50 kg     2     4     6  
>=50 kg     15     30     45  
[1]

Yes if 3 or more risk factors are present:

1) Abdominal obesity 2) Triglycerides >=150 mg/dl * 3) High density lipoprotein cholesterol (men <40 mg/dl) (women <50 mg/dl) * 4) Systolic blood pressure >=130 or diastolic >=85 mmHg * 5) Fasting glucose >=100 mg/dl *

* = or on medication for condition

[2] Participants who weighed <50 kg received the lower dose of 160 mg mipomersen or matching placebo. All other patients received a dose of 200 mg or matching placebo.



  Outcome Measures
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1.  Primary:   Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

2.  Primary:   LDL-C at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

3.  Secondary:   Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

4.  Secondary:   Apo-B at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ) ]

5.  Secondary:   Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

6.  Secondary:   Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

7.  Secondary:   Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

8.  Secondary:   Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

9.  Other Pre-specified:   Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

10.  Other Pre-specified:   Triglycerides at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

11.  Other Pre-specified:   Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

12.  Other Pre-specified:   Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

13.  Other Pre-specified:   Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

14.  Other Pre-specified:   VLDL-C at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

15.  Other Pre-specified:   Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol (LDL-C) to High-density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

16.  Other Pre-specified:   Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

17.  Other Pre-specified:   Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

18.  Other Pre-specified:   Apo-A1 at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

19.  Other Pre-specified:   Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]

20.  Other Pre-specified:   HDL-C at Baseline and the Primary Efficacy Time Point (PET)   [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  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.


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


No publications provided by Genzyme, a Sanofi Company

Publications automatically indexed to this study:

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00607373     History of Changes
Other Study ID Numbers: 301012CS5, 2005-003449-15
Study First Received: January 22, 2008
Results First Received: February 15, 2013
Last Updated: May 30, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
South Africa: Medicines Control Council
Singapore: Health Sciences Authority
Taiwan: Department of Health
Brazil: National Health Surveillance Agency