Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01475825




Registration number
NCT01475825
Ethics application status
Date submitted
17/11/2011
Date registered
21/11/2011
Date last updated
26/03/2019

Titles & IDs
Public title
A Study of the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients With Familial Hypercholesterolemia and Inadequately Controlled Low-Density Lipoprotein Cholesterol
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Followed by an Open-Label Continuation Period to Assess the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients With Familial Hypercholesterolemia and Inadequately Controlled Low-Density Lipoprotein Cholesterol
Secondary ID [1] 0 0
2011-001480-42
Secondary ID [2] 0 0
MIPO3801011
Universal Trial Number (UTN)
Trial acronym
FOCUS FH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolemia 0 0
Heterozygous Familial 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - mipomersen sodium 200 mg
Treatment: Drugs - Placebo
Treatment: Drugs - mipomersen sodium 70 mg

Experimental: Regimen A: Mipomersen - Subcutaneous injection of mipomersen 200 mg once weekly

Placebo Comparator: Regimen A: Placebo - Placebo matching subcutaneous injection once weekly.

Experimental: Regimen B: Mipomersen - Subcutaneous injection of mipomersen 70 mg thrice weekly.

Placebo Comparator: Regimen B: Placebo - Placebo matching subcutaneous injection thrice weekly.


Treatment: Drugs: mipomersen sodium 200 mg
Subcutaneous mipomersen 200 mg once weekly

Treatment: Drugs: Placebo
Placebo vehicle for subcutaneous injection.

Treatment: Drugs: mipomersen sodium 70 mg
Subcutaneous mipomersen 70 mg thrice weekly
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1
Timepoint [1] 0 0
Baseline and Week 61
Secondary outcome [1] 0 0
Percent Change From Baseline To PET In LDL-C In Cohort 2
Timepoint [1] 0 0
Baseline, PET (up to 60 weeks)
Secondary outcome [2] 0 0
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 1
Timepoint [2] 0 0
Baseline and Week 61
Secondary outcome [3] 0 0
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 2
Timepoint [3] 0 0
Baseline and Week 61
Secondary outcome [4] 0 0
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 1
Timepoint [4] 0 0
Baseline and Week 61
Secondary outcome [5] 0 0
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 2
Timepoint [5] 0 0
Baseline and Week 61

Eligibility
Key inclusion criteria
- Diagnosis of severe hypercholesterolemia (LDL-C =300 mg/dL (7.77 mmol/L) or LDL-C =200
mg/dL (5.18 mmol/L) with documented coronary heart disease (CHD) or CHD risk
equivalents, or diagnosis of Heterozygous Familial Hypercholesterolemia and LDL-C =160
mg/dL (4.14 mmol/L) and <200 mg/dL (5.18 mmol/L))

- On stable, maximally tolerated, statin therapy for at least 12 weeks or if statin
intolerant, on at least 1 medication from another class of hypolipidemic agents (i.e.,
bile acid sequestrants, niacin/nicotinic acid, cholesterol absorption inhibitors,
fibrates).

- On stable, low fat diet for 12 weeks

- Body mass index (BMI) =40 kg/m2 and stable weight for > 6 weeks
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Significant health problems in the recent past including heart attack, stroke,
coronary syndrome, unstable angina, heart failure, significant arrhythmia,
hypertension, blood disorders, liver disease, cancer, digestive disorders, Type I
diabetes, or uncontrolled Type II diabetes

- Apheresis within 3 months prior to Screening or expected to start apheresis during the
treatment phase

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/12/2015
Sample size
Target
Accrual to date
Final
309
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Perth
Recruitment hospital [2] 0 0
- South Brisbane
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
Argentina
State/province [19] 0 0
Ciudad Autonoma de Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
Cordoba
Country [21] 0 0
Belgium
State/province [21] 0 0
Edegem
Country [22] 0 0
Belgium
State/province [22] 0 0
Haine St. Paul
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Brazil
State/province [24] 0 0
Rio de Janeiro
Country [25] 0 0
Brazil
State/province [25] 0 0
Sao Paulo
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
Croatia
State/province [27] 0 0
Osijek
Country [28] 0 0
Croatia
State/province [28] 0 0
Zagreb
Country [29] 0 0
Czechia
State/province [29] 0 0
Hradec Kralove
Country [30] 0 0
Czechia
State/province [30] 0 0
Praha 1
Country [31] 0 0
Denmark
State/province [31] 0 0
Aarhus
Country [32] 0 0
Denmark
State/province [32] 0 0
Viborg
Country [33] 0 0
Germany
State/province [33] 0 0
Aachen
Country [34] 0 0
Germany
State/province [34] 0 0
Berlin
Country [35] 0 0
Germany
State/province [35] 0 0
Freiburg
Country [36] 0 0
Germany
State/province [36] 0 0
Hamburg
Country [37] 0 0
Germany
State/province [37] 0 0
Heidelberg
Country [38] 0 0
Germany
State/province [38] 0 0
Koeln
Country [39] 0 0
Germany
State/province [39] 0 0
Magdeburg
Country [40] 0 0
Greece
State/province [40] 0 0
Ioannina
Country [41] 0 0
Greece
State/province [41] 0 0
Kallithea
Country [42] 0 0
Hong Kong
State/province [42] 0 0
Hong Kong
Country [43] 0 0
Hungary
State/province [43] 0 0
Baja
Country [44] 0 0
Hungary
State/province [44] 0 0
Budapest
Country [45] 0 0
Hungary
State/province [45] 0 0
Debrecen
Country [46] 0 0
India
State/province [46] 0 0
New Delhi
Country [47] 0 0
Israel
State/province [47] 0 0
Holon
Country [48] 0 0
Israel
State/province [48] 0 0
Kfar Saba
Country [49] 0 0
Israel
State/province [49] 0 0
Ofakim
Country [50] 0 0
Italy
State/province [50] 0 0
Bologna
Country [51] 0 0
Italy
State/province [51] 0 0
Napoli
Country [52] 0 0
Italy
State/province [52] 0 0
Padova
Country [53] 0 0
Italy
State/province [53] 0 0
Palermo
Country [54] 0 0
Italy
State/province [54] 0 0
Pisa
Country [55] 0 0
Italy
State/province [55] 0 0
Roma
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Seoul
Country [57] 0 0
Malaysia
State/province [57] 0 0
Kuala Lumpur
Country [58] 0 0
Malaysia
State/province [58] 0 0
Kubang Kerian
Country [59] 0 0
Netherlands
State/province [59] 0 0
Alkmaar
Country [60] 0 0
Netherlands
State/province [60] 0 0
Amsterdam
Country [61] 0 0
Netherlands
State/province [61] 0 0
Maastricht
Country [62] 0 0
Netherlands
State/province [62] 0 0
Nijmegen
Country [63] 0 0
Netherlands
State/province [63] 0 0
Utrecht
Country [64] 0 0
Netherlands
State/province [64] 0 0
Waalwijk
Country [65] 0 0
New Zealand
State/province [65] 0 0
Christchurch
Country [66] 0 0
Norway
State/province [66] 0 0
Bodo
Country [67] 0 0
Norway
State/province [67] 0 0
Oslo
Country [68] 0 0
Norway
State/province [68] 0 0
Sandefjord
Country [69] 0 0
Poland
State/province [69] 0 0
Bialystok
Country [70] 0 0
Poland
State/province [70] 0 0
Gdansk
Country [71] 0 0
Poland
State/province [71] 0 0
Katowice
Country [72] 0 0
Poland
State/province [72] 0 0
Krakow
Country [73] 0 0
Poland
State/province [73] 0 0
Naleczow
Country [74] 0 0
Poland
State/province [74] 0 0
Poznan
Country [75] 0 0
Poland
State/province [75] 0 0
Sopot
Country [76] 0 0
Poland
State/province [76] 0 0
Szczecin
Country [77] 0 0
Poland
State/province [77] 0 0
Warszawa
Country [78] 0 0
Poland
State/province [78] 0 0
Wroclaw
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Barnaul
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Kemerovo
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Moscow
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Novosibirsk
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Petrozavodsk
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Ryazan
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Saint Petersburg
Country [86] 0 0
Russian Federation
State/province [86] 0 0
St-Petersburg
Country [87] 0 0
Russian Federation
State/province [87] 0 0
St. Petersburg
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Tomsk
Country [89] 0 0
Russian Federation
State/province [89] 0 0
Yaroslavl
Country [90] 0 0
South Africa
State/province [90] 0 0
Cape Town
Country [91] 0 0
South Africa
State/province [91] 0 0
Pretoria
Country [92] 0 0
Spain
State/province [92] 0 0
Madrid
Country [93] 0 0
Sweden
State/province [93] 0 0
Stockholm
Country [94] 0 0
Taiwan
State/province [94] 0 0
New Taipei City
Country [95] 0 0
Taiwan
State/province [95] 0 0
Taipei
Country [96] 0 0
Turkey
State/province [96] 0 0
Ankara
Country [97] 0 0
Turkey
State/province [97] 0 0
Istanbul
Country [98] 0 0
Turkey
State/province [98] 0 0
Izmir
Country [99] 0 0
Turkey
State/province [99] 0 0
Sivas
Country [100] 0 0
Ukraine
State/province [100] 0 0
Ivano-Frankivsk
Country [101] 0 0
Ukraine
State/province [101] 0 0
Kiev
Country [102] 0 0
Ukraine
State/province [102] 0 0
Kyiv
Country [103] 0 0
Ukraine
State/province [103] 0 0
Odesa
Country [104] 0 0
Ukraine
State/province [104] 0 0
Odessa
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Birmingham
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Cardiff
Country [107] 0 0
United Kingdom
State/province [107] 0 0
Liverpool
Country [108] 0 0
United Kingdom
State/province [108] 0 0
London
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Manchester
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Oldham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Kastle Therapeutics, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Primary objective:

Determine whether mipomersen (ISIS 301012) significantly reduces atherogenic lipid levels in
patients with severe heterozygous familial hypercholesterolemia (severe HeFH), defined as
low-density lipoprotein cholesterol (LDL-C) levels =200 mg/dL plus the presence of coronary
heart disease (CHD)/risk equivalents or LDL-C levels =300 mg/dL regardless of the presence of
CHD/risk equivalents (referred to as Cohort 1) compared to placebo. Two different mipomersen
dosing regimens will be studied: subcutaneous (SC) mipomersen 200 mg once weekly versus
placebo, and SC mipomersen 70 mg thrice weekly versus placebo.

Secondary Objectives:

- Determine whether there are qualitative differences between the safety profiles of the 2
dosing regimens and placebo in Cohort 1, patients with HeFH with LDL-C levels =160 mg/dL
and <200 mg/dL plus the presence of CHD/risk equivalents (referred to as Cohort 2), and
the overall study population

- Determine whether there are qualitative differences between the tolerability of the 2
dosing regimens and placebo in Cohort 1, Cohort 2, and the overall study population

- Further characterize the pharmacokinetics (PK) of the 2 dosing regimens in Cohort 1,
Cohort 2, and the overall study population

- Determine whether the 2 mipomersen dosing regimens significantly reduce atherogenic
lipid levels in Cohort 2 compared to placebo

- Obtain additional data regarding ongoing safety and efficacy of mipomersen in patients
with FH and inadequately controlled LDL-C who complete the primary efficacy assessment
visit (PET) in the Blinded Treatment Period and continue treatment in Open-Label
Continuation Period
Trial website
https://clinicaltrials.gov/ct2/show/NCT01475825
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Genzyme, a Sanofi Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01475825