Clinical trial NCT01954394: Open Label Study of Long Term Safety Evaluation of Alirocumab
Official title: Open-Label Extension Study of EFC12492, R727-CL-1112, EFC12732 and LTS11717 Studies to Assess the Long-Term Safety and Efficacy of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2013-10-01
Enrollment: 986
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To assess the long-term safety of alirocumab (SAR236553/REGN727) when added to lipid-lowering therapy in participants with heterozygous familial hypercholesterolemia (heFH) who had completed EFC12492 (NCT01623115), R727-CL-1112 (NCT01709500), EFC12732 (NCT01617655) and LTS11717 (NCT01507831).

Secondary Objectives:

* To evaluate the long-term efficacy of alirocumab on lipid parameters.
* To evaluate the long-term immunogenicity of alirocumab.

Detailed description: The maximum study duration will be 176 weeks per participant.

Eligibility criteria: Inclusion criteria:

Participants with heFH who had completed one of the four parent studies (EFC12492, R727-CL-1112, EFC12732 and LTS11717).

Exclusion criteria:

Significant protocol deviation in the parent study; Any permanent treatment discontinuation from the parent study.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Percentage of Participants Who Experienced Adverse Events (AEs)
timeFrame: Up to 10 weeks after last study drug administration (maximum of 176 weeks)
Secondary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Weeks 8, 24, 48, 72, 96, 120, 144 and 168
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) Over Time
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) Over Time
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Percentage of Participants With Calculated LDL-C <70 mg/dL (1.81mmol/L) and/or >=50% Reduction in Calculated LDL-C From Baseline (if Calculated LDL-C >=70 mg/dL [1.81mmol/L]) Over Time
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Percent Change From Baseline in Total-cholesterol at Weeks 8, 24, 48, 72, 96, 120, 144 and 168
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Percent Change From Baseline in Fasting Triglycerides (TGs) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168
timeFrame: Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168
measure: Percent Change From Baseline in Lipoprotein (a) at Weeks 48, 96, 144 and 168
timeFrame: Parent Baseline, Weeks 48, 96, 144, and 168
measure: Percent Change From Baseline in Apolipoprotein-B (Apo-B) at Weeks 48, 96, 144, and 168
timeFrame: Parent Baseline, Weeks 48, 96, 144, and 168
measure: Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Weeks 48, 96, 144, and 168
timeFrame: Parent Baseline, Weeks 48, 96, 144, and 168
measure: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 48, 96, 144, and 168
timeFrame: Parent Baseline, Weeks 48, 96, 144, and 168
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Investigational Site Number 840321
state: Alabama
city: Tempe
country: United States
facility: Investigational Site Number 840341
state: Arizona
city: Bell Gardens
country: United States
facility: Investigational Site Number 840334
state: California
city: Fountain Valley
country: United States
facility: Investigational Site Number 840319
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840336
state: California
city: Mission Viejo
country: United States
facility: Investigational Site Number 840339
state: California
city: Newport Beach
country: United States
facility: Investigational Site Number 840337
state: California
city: Golden
country: United States
facility: Investigational Site Number 840306
state: Colorado
city: Washington
country: United States
facility: Investigational Site Number 840328
state: District of Columbia
city: Atlantis
country: United States
facility: Investigational Site Number 840344
state: Florida
city: Clearwater
country: United States
facility: Investigational Site Number 840353
state: Florida
city: Fort Lauderdale
country: United States
facility: Investigational Site Number 840318
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840327
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840309
state: Florida
city: Sarasota
country: United States
facility: Investigational Site Number 840351
state: Florida
city: Evanston
country: United States
facility: Investigational Site Number 840315
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Investigational Site Number 840305
state: Illinois
city: Iowa City
country: United States
facility: Investigational Site Number 840333
state: Iowa
city: Kansas City
country: United States
facility: Investigational Site Number 840329
state: Kansas
city: Auburn
country: United States
facility: Investigational Site Number 840345
state: Maine
city: Biddeford
country: United States
facility: Investigational Site Number 840338
state: Maine
city: Boston
country: United States
facility: Investigational Site Number 840322
state: Massachusetts
city: Framingham
country: United States
facility: Investigational Site Number 840346
state: Massachusetts
city: Saint Louis
country: United States
facility: Investigational Site Number 840317
state: Missouri
city: Saint Louis
country: United States
facility: Investigational Site Number 840349
state: Missouri
city: Morristown
country: United States
facility: Investigational Site Number 840314
state: New Jersey
city: New York
country: United States
facility: Investigational Site Number 840316
state: New York
city: Poughkeepsie
country: United States
facility: Investigational Site Number 840324
state: New York
city: Charlotte
country: United States
facility: Investigational Site Number 840303
state: North Carolina
city: Durham
country: United States
facility: Investigational Site Number 840320
state: North Carolina
city: Raleigh
country: United States
facility: Investigational Site Number 840348
state: North Carolina
city: Cincinnati
country: United States
facility: Investigational Site Number 840340
state: Ohio
city: Marion
country: United States
facility: Investigational Site Number 840302
state: Ohio
city: Portland
country: United States
facility: Investigational Site Number 840330
state: Oregon
city: Beaver
country: United States
facility: Investigational Site Number 840352
state: Pennsylvania
city: Philadelphia
country: United States
facility: Investigational Site Number 840308
state: Pennsylvania
city: Scranton
country: United States
facility: Investigational Site Number 840342
state: Pennsylvania
city: Summerville
country: United States
facility: Investigational Site Number 840304
state: South Carolina
city: Dallas
country: United States
facility: Investigational Site Number 840311
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840312
state: Texas
city: Fort Worth
country: United States
facility: Investigational Site Number 840301
state: Texas
city: Bountiful
country: United States
facility: Investigational Site Number 840343
state: Utah
city: Chesapeake
country: United States
facility: Investigational Site Number 840354
state: Virginia
city: Spokane
country: United States
facility: Investigational Site Number 840350
state: Washington
city: Caba
country: Argentina
facility: Investigational Site Number 032302
city: Coronel Suarez
country: Argentina
facility: Investigational Site Number 032301
city: Graz
country: Austria
facility: Investigational Site Number 040302
city: Sankt Stefan
country: Austria
facility: Investigational Site Number 040303
city: Wien
country: Austria
facility: Investigational Site Number 040301
city: Natoye
country: Belgium
facility: Investigational Site Number 056301
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100302
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100301
city: Chicoutimi
country: Canada
facility: Investigational Site Number 124303
city: Montreal
country: Canada
facility: Investigational Site Number 124302
city: Quebec
country: Canada
facility: Investigational Site Number 124301
city: Sherbrooke
country: Canada
facility: Investigational Site Number 124306
city: Toronto
country: Canada
facility: Investigational Site Number 124305
city: Victoria
country: Canada
facility: Investigational Site Number 124304
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number 203307
city: Praha 2
country: Czechia
facility: Investigational Site Number 203305
city: Praha 4
country: Czechia
facility: Investigational Site Number 203301
city: Praha 5 - Motol
country: Czechia
facility: Investigational Site Number 203306
city: Praha 8
country: Czechia
facility: Investigational Site Number 203303
city: Trutnov
country: Czechia
facility: Investigational Site Number 203309
city: Uherske Hradiste
country: Czechia
facility: Investigational Site Number 203304
city: Zlin
country: Czechia
facility: Investigational Site Number 203302
city: Aalborg
country: Denmark
facility: Investigational Site Number 208301
city: Aarhus
country: Denmark
facility: Investigational Site Number 208306
city: Esbjerg
country: Denmark
facility: Investigational Site Number 208302
city: Roskilde
country: Denmark
facility: Investigational Site Number 208303
city: Svendborg
country: Denmark
facility: Investigational Site Number 208304
city: Joensuu
country: Finland
facility: Investigational Site Number 246302
city: Kokkola
country: Finland
facility: Investigational Site Number 246301
city: Vantaa
country: Finland
facility: Investigational Site Number 246304
city: Dijon
country: France
facility: Investigational Site Number 250303
city: Lille Cedex
country: France
facility: Investigational Site Number 250304
city: Nantes
country: France
facility: Investigational Site Number 250302
city: Paris
country: France
facility: Investigational Site Number 250301
city: Pessac
country: France
facility: Investigational Site Number 250305
city: Rennes
country: France
facility: Investigational Site Number 250306
city: Berlin
country: Germany
facility: Investigational Site Number 276302
city: Frankfurt A.M.
country: Germany
facility: Investigational Site Number 276305
city: Leipzig
country: Germany
facility: Investigational Site Number 276306
city: Magdeburg
country: Germany
facility: Investigational Site Number 276301
city: Witten
country: Germany
facility: Investigational Site Number 276307
city: Baja
country: Hungary
facility: Investigational Site Number 348301
city: Holon
country: Israel
facility: Investigational Site Number 376302
city: Jerusalem
country: Israel
facility: Investigational Site Number 376304
city: Safed
country: Israel
facility: Investigational Site Number 376303
city: Tel Hashomer
country: Israel
facility: Investigational Site Number 376301
city: Chieti
country: Italy
facility: Investigational Site Number 380302
city: Milano
country: Italy
facility: Investigational Site Number 380304
city: Napoli
country: Italy
facility: Investigational Site Number 380303
city: Palermo
country: Italy
facility: Investigational Site Number 380301
city: Mexico
country: Mexico
facility: Investigational Site Number 484301
city: Alkmaar
country: Netherlands
facility: Investigational Site Number 528317
city: Amsterdam-Zuidoost
country: Netherlands
facility: Investigational Site Number 528301
city: Apeldoorn
country: Netherlands
facility: Investigational Site Number 528320
city: Delfzijl
country: Netherlands
facility: Investigational Site Number 528309
city: Eindhoven
country: Netherlands
facility: Investigational Site Number 528313
city: Enschede
country: Netherlands
facility: Investigational Site Number 528319
city: Goes
country: Netherlands
facility: Investigational Site Number 528322
city: Groningen
country: Netherlands
facility: Investigational Site Number 528325
city: Groningen
country: Netherlands
facility: Investigational Site Number 528302
city: Hoogeveen
country: Netherlands
facility: Investigational Site Number 528324
city: Hoorn
country: Netherlands
facility: Investigational Site Number 528318
city: Leiden
country: Netherlands
facility: Investigational Site Number 528305
city: Maastricht
country: Netherlands
facility: Investigational Site Number 528311
city: Nijmegen
country: Netherlands
facility: Investigational Site Number 528312
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528315
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528326
city: Utrecht
country: Netherlands
facility: Investigational Site Number 528303
city: Utrecht
country: Netherlands
facility: Investigational Site Number 528323
city: Venlo
country: Netherlands
facility: Investigational Site Number 528321
city: Waalwijk
country: Netherlands
facility: Investigational Site Number 528316
city: Bodo
country: Norway
facility: Investigational Site Number 578301
city: Oslo
country: Norway
facility: Investigational Site Number 578305
city: Oslo
country: Norway
facility: Investigational Site Number 578304
city: Funchal
country: Portugal
facility: Investigational Site Number 620302
city: Lisboa
country: Portugal
facility: Investigational Site Number 620301
city: Timisoara
country: Romania
facility: Investigational Site Number 642302
city: Arkhangelsk
country: Russian Federation
facility: Investigational Site Number 643304
city: Kazan
country: Russian Federation
facility: Investigational Site Number 643303
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643302
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643308
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643305
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 643310
city: St Petersbourg
country: Russian Federation
facility: Investigational Site Number 643301
city: St. Petersburg
country: Russian Federation
facility: Investigational Site Number 643306
city: St.Petersburg
country: Russian Federation
facility: Investigational Site Number 643312
city: Bellville
country: South Africa
facility: Investigational Site Number 710311
city: Bloemfontein
country: South Africa
facility: Investigational Site Number 710307
city: Cape Town
country: South Africa
facility: Investigational Site Number 710306
city: Cape Town
country: South Africa
facility: Investigational Site Number 710302
city: Centurion
country: South Africa
facility: Investigational Site Number 710309
city: Parktown
country: South Africa
facility: Investigational Site Number 710312
city: Parow
country: South Africa
facility: Investigational Site Number 710304
city: Pretoria
country: South Africa
facility: Investigational Site Number 710313
city: Pretoria
country: South Africa
facility: Investigational Site Number 710303
city: Pretoria
country: South Africa
facility: Investigational Site Number 710305
city: Pretoria
country: South Africa
facility: Investigational Site Number 710314
city: Roodepoort
country: South Africa
facility: Investigational Site Number 710315
city: Somerset West
country: South Africa
facility: Investigational Site Number 710310
city: Witbank
country: South Africa
facility: Investigational Site Number 710308
city: A Coruna
country: Spain
facility: Investigational Site Number 724303
city: Barcelona
country: Spain
facility: Investigational Site Number 724308
city: Córdoba
country: Spain
facility: Investigational Site Number 724306
city: Granada
country: Spain
facility: Investigational Site Number 724312
city: Hospitalet De Llobregat
country: Spain
facility: Investigational Site Number 724307
city: Madrid
country: Spain
facility: Investigational Site Number 724301
city: Madrid
country: Spain
facility: Investigational Site Number 724309
city: Madrid
country: Spain
facility: Investigational Site Number 724305
city: Madrid
country: Spain
facility: Investigational Site Number 724311
city: Málaga
country: Spain
facility: Investigational Site Number 724314
city: Quart De Poblet
country: Spain
facility: Investigational Site Number 724315
city: Sabadell
country: Spain
facility: Investigational Site Number 724310
city: Sevilla
country: Spain
facility: Investigational Site Number 724313
city: Tarragona
country: Spain
facility: Investigational Site Number 724304
city: Zaragoza
country: Spain
facility: Investigational Site Number 724302
city: Goteborg
country: Sweden
facility: Investigational Site Number 752302
city: Stockholm
country: Sweden
facility: Investigational Site Number 752301
city: Stockholm
country: Sweden
facility: Investigational Site Number 752304
city: Birmingham
country: United Kingdom
facility: Investigational Site Number 826318
city: Brighton
country: United Kingdom
facility: Investigational Site Number 826304
city: Bristol
country: United Kingdom
facility: Investigational Site Number 826301
city: Cambridge
country: United Kingdom
facility: Investigational Site Number 826311
city: Cardiff
country: United Kingdom
facility: Investigational Site Number 826310
city: Dundee
country: United Kingdom
facility: Investigational Site Number 826302
city: Liverpool
country: United Kingdom
facility: Investigational Site Number 826317
city: Liverpool
country: United Kingdom
facility: Investigational Site Number 826306
city: Manchester
country: United Kingdom
facility: Investigational Site Number 826312
city: Manchester
country: United Kingdom
facility: Investigational Site Number 826303
city: Middlesex
country: United Kingdom
facility: Investigational Site Number 826305
city: Newcastle Upon Tyne
country: United Kingdom
facility: Investigational Site Number 826313
city: Reading
country: United Kingdom
facility: Investigational Site Number 826309
city: West Bromwich
country: United Kingdom
facility: Investigational Site Number 826315
city: West Bromwich
country: United Kingdom
facility: Investigational Site Number 826316
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Dufour R, Hovingh GK, Guyton JR, Langslet G, Baccara-Dinet MT, Din-Bell C, Manvelian G, Farnier M. Individualized low-density lipoprotein cholesterol reduction with alirocumab titration strategy in heterozygous familial hypercholesterolemia: Results from an open-label extension of the ODYSSEY LONG TERM trial. J Clin Lipidol. 2019 Jan-Feb;13(1):138-147. doi: 10.1016/j.jacl.2018.11.007. Epub 2018 Nov 30.
citation: Farnier M, Hovingh GK, Langslet G, Dufour R, Baccara-Dinet MT, Din-Bell C, Manvelian G, Guyton JR. Long-term safety and efficacy of alirocumab in patients with heterozygous familial hypercholesterolemia: An open-label extension of the ODYSSEY program. Atherosclerosis. 2018 Nov;278:307-314. doi: 10.1016/j.atherosclerosis.2018.08.036. Epub 2018 Sep 1.
citation: Hovingh GK, Guyton JR, Langslet G, Dufour R, Baccara-Dinet MT, Din-Bell C, Manvelian G, Farnier M. Alirocumab dosing patterns during 40 months of open-label treatment in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2018 Nov-Dec;12(6):1463-1470. doi: 10.1016/j.jacl.2018.08.011. Epub 2018 Aug 30.