Safety, Tolerability, and Effect of Alirocumab in High Cardiovascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-modifying Therapies (ODYSSEY APPRISE)
- Conditions
- Hypercholesterolemia
- Interventions
- Drug: placebo (for injection training only)
- Registration Number
- NCT02476006
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To provide participants with severe hypercholesterolemia at risk for subsequent cardiovascular (CV) events and not adequately controlled with currently available lipid-modifying therapy (LMT) access to alirocumab ahead of commercial availability and to document the overall safety and tolerability of alirocumab in this participant population.
Secondary Objectives:
To document the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels as well as non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels after 12 weeks of treatment.
To document participant's acceptability of self-injection (Self Injection Assessment Questionnaire, SIAQ).
- Detailed Description
The study duration included a screening period of up to 3 weeks, a treatment period of a minimum of 12 weeks and up to a maximum of 120 weeks (30 months), and at least 2 weeks after the last study treatment injection.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 998
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Alirocumab ALIROCUMAB SAR236553 (REGN727) Participants received Alirocumab 150 milligram (mg) subcutaneously (SC) once every two weeks (Q2W) or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response. Alirocumab placebo (for injection training only) Participants received Alirocumab 150 milligram (mg) subcutaneously (SC) once every two weeks (Q2W) or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response. Alirocumab ezetimibe Participants received Alirocumab 150 milligram (mg) subcutaneously (SC) once every two weeks (Q2W) or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response. Alirocumab atorvastatin Participants received Alirocumab 150 milligram (mg) subcutaneously (SC) once every two weeks (Q2W) or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response. Alirocumab rosuvastatin Participants received Alirocumab 150 milligram (mg) subcutaneously (SC) once every two weeks (Q2W) or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response. Alirocumab simvastatin Participants received Alirocumab 150 milligram (mg) subcutaneously (SC) once every two weeks (Q2W) or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) From first injection of investigational medicinal product (IMP) up to 2 weeks after last dose of study drug (Week 120) Adverse Event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs) were defined as AEs that that developed or worsened or became serious during the TEAE period (time from the first injection of study drug up to the day of the last injection of study drug + 14 days). A Serious Adverse Event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 12 At Week 12 LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached calculated LDL-C \<70 mg/dL (1.81 mmol/L) at week 12 were reported.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 Baseline, Week 12 Baseline value was defined as the last observation before the first dose of the treatment.
Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections Baseline (Pre-SIAQ), Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96 Pre-SIAQ: self-completed before first self-injection \& Post-SIAQ: self-completed after self-injection. Pre-SIAQ consisted of 7 items grouped into 3 domains:feelings about injections,self-confidence \& satisfaction with self-injection. Post-SIAQ consisted of 21 items grouped into 6 domains:feelings about injections,self-image,self-confidence,injection-site reactions,ease of use \& satisfaction with self-injection. Participants rated each item on 5-point (or 6-point) semantic Likert-type scale, where lower numbers indicate a worse experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience). Transformed scores for items contributing to a domain were then averaged into a domain score. Each domain score ranges from 0 (worst experience) to 10 (best experience), higher score=better acceptability. Domain scores common to the Pre \& Post SIAQ were analyzed on participants belonging to Pre \& Post-SIAQ population and are reported.
Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 At Week 12 LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached calculated LDL-C \<100 mg/dL (2.59 mmol/L) at week 12 were reported.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12 Baseline, Week 12 Baseline value was defined as the last observation before the first dose of the treatment.
Percent Change From Baseline in Triglycerides at Week 12 Baseline, Week 12 Baseline value was defined as the last observation before the first dose of the treatment.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) and/or >=50% Reduction From Baseline in LDL-C at Week 12 At Week 12 LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached LDL-C \<70 mg/dL at Week 12 and/or \>=50% reduction from baseline in LDL-C at Week 12 are reported.
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12 Baseline, Week 12 Baseline value was defined as the last observation before the first dose of the treatment.
Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96 SIAQ: contained 2 modules: Pre-SIAQ and Post-SIAQ. Post-SIAQ: self-completed after self-injection. Post-SIAQ consisted of 21 items grouped into 6 domains: feelings about injections, self-image, self-confidence, injection-site reactions, ease of use \& satisfaction with self-injection. Participants rated each item on 5-point (or 6-point) semantic Likert-type scale, where lower numbers indicated a worse experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience) for each item. Transformed scores for items contributing to a domain were then averaged into a domain score. Each domain score ranges from 0 (worst experience) to 10 (best experience), higher score=better acceptability. Domain scores which are not in common with Pre-SIAQ were analyzed on the Post-SIAQ population and are reported here.
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 Baseline, Week 12 Calculated LDL-C values were obtained using the Friedewald formula. Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - \[Triglyceride/5\]). Baseline value was defined as the last observation before the first dose of the treatment.
Trial Locations
- Locations (153)
Investigational Site Number 040001
🇦🇹Graz, Austria
Investigational Site Number 040002
🇦🇹Wien, Austria
Investigational Site Number 040010
🇦🇹Wien, Austria
Investigational Site Number 040003
🇦🇹Wien, Austria
Investigational Site Number 056006
🇧🇪Charleroi, Belgium
Investigational Site Number 056015
🇧🇪Kortrijk, Belgium
Investigational Site Number 040008
🇦🇹Innsbruck, Austria
Investigational Site Number 056005
🇧🇪Aalst, Belgium
Investigational Site Number 056018
🇧🇪Antwerpen, Belgium
Investigational Site Number 056019
🇧🇪Genk, Belgium
Investigational Site Number 056004
🇧🇪Leuven, Belgium
Investigational Site Number 056014
🇧🇪Liège, Belgium
Investigational Site Number 040007
🇦🇹Wien, Austria
Investigational Site Number 056013
🇧🇪Brugge, Belgium
Investigational Site Number 056010
🇧🇪Brussel, Belgium
Investigational Site Number 056016
🇧🇪Roeselare, Belgium
Investigational Site Number 756003
🇨🇭St. Gallen, Switzerland
Investigational Site Number 040004
🇦🇹Wien, Austria
Investigational Site Number 056002
🇧🇪Haine St Paul, Belgium
Investigational Site Number 056009
🇧🇪La Louvière, Belgium
Investigational Site Number 056011
🇧🇪Overpelt, Belgium
Investigational Site Number 756001
🇨🇭Zürich, Switzerland
Investigational Site Number 348002
🇭🇺Debrecen, Hungary
Investigational Site Number 705001
🇸🇮Maribor, Slovenia
Investigational Site Number 756004
🇨🇭Reinach, Switzerland
Investigational Site Number 250033
🇫🇷Jossigny, France
Investigational Site Number 250004
🇫🇷Lille, France
Investigational Site Number 250037
🇫🇷Limoges Cedex, France
Investigational Site Number 250022
🇫🇷Nantes, France
Investigational Site Number 250039
🇫🇷NIMES Cedex 9, France
Investigational Site Number 250044
🇫🇷PARIS Cedex 04, France
Investigational Site Number 250041
🇫🇷Paris, France
Investigational Site Number 250051
🇫🇷Pessac, France
Investigational Site Number 250026
🇫🇷Paris, France
Investigational Site Number 250011
🇫🇷POITIERS Cedex, France
Investigational Site Number 250010
🇫🇷Reims Cedex, France
Investigational Site Number 250008
🇫🇷Rennes, France
Investigational Site Number 250018
🇫🇷Rouen, France
Investigational Site Number 250023
🇫🇷Saint-Mandé, France
Investigational Site Number 250046
🇫🇷Toulouse Cedex 3, France
Investigational Site Number 250025
🇫🇷TOULOUSE Cedex 9, France
Investigational Site Number 250007
🇫🇷Tours, France
Investigational Site Number 250019
🇫🇷Venissieux, France
Investigational Site Number 250050
🇫🇷VICHY Cedex, France
Investigational Site Number 056007
🇧🇪Edegem, Belgium
Investigational Site Number 208001
🇩🇰Esbjerg, Denmark
Investigational Site Number 208003
🇩🇰Ålborg, Denmark
Investigational Site Number 250034
🇫🇷Auxerre, France
Investigational Site Number 250015
🇫🇷Caen, France
Investigational Site Number 250032
🇫🇷Coudray, France
Investigational Site Number 250002
🇫🇷Dijon, France
Investigational Site Number 250012
🇫🇷Grenoble, France
Investigational Site Number 203002
🇨🇿Hradec Kralove, Czechia
Investigational Site Number 250038
🇫🇷GRENOBLE cedex, France
Investigational Site Number 246001
🇫🇮Varkaus, Finland
Investigational Site Number 250016
🇫🇷Avignon, France
Investigational Site Number 250030
🇫🇷Bobigny, France
Investigational Site Number 250045
🇫🇷BORDEAUX Cedex, France
Investigational Site Number 250013
🇫🇷Corbeil Essonnes, France
Investigational Site Number 250021
🇫🇷Bayonne, France
Investigational Site Number 203004
🇨🇿Brno, Czechia
Investigational Site Number 203005
🇨🇿Uherske Hradiste, Czechia
Investigational Site Number 203001
🇨🇿Praha, Czechia
Investigational Site Number 124009
🇨🇦Woodstock, Canada
Investigational Site Number 246003
🇫🇮Turku, Finland
Investigational Site Number 300001
🇬🇷Kallithea, Greece
Investigational Site Number 250014
🇫🇷Paris, France
Investigational Site Number 250027
🇫🇷Amiens Cedex 1, France
Investigational Site Number 276001
🇩🇪Berlin, Germany
Investigational Site Number 250049
🇫🇷Brest Cedex, France
Investigational Site Number 250054
🇫🇷Bron, France
Investigational Site Number 250047
🇫🇷Clermont Ferrand, France
Investigational Site Number 250028
🇫🇷Marseille, France
Investigational Site Number 250040
🇫🇷Dijon, France
Investigational Site Number 208002
🇩🇰Roskilde, Denmark
Investigational Site Number 250042
🇫🇷Lille, France
Investigational Site Number 616003
🇵🇱Krakow, Poland
Investigational Site Number 616002
🇵🇱Warszawa, Poland
Investigational Site Number 642-001
🇷🇴Timisoara, Romania
Investigational Site Number 703001
🇸🇰Kosice, Slovakia
Investigational Site Number 250057
🇫🇷Lyon, France
Investigational Site Number 348001
🇭🇺Budapest, Hungary
Investigational Site Number 250035
🇫🇷LE CHESNAY Cedex, France
Investigational Site Number 250036
🇫🇷Lens, France
Investigational Site Number 250048
🇫🇷Marseille Cedex 05, France
Investigational Site Number 300003
🇬🇷Ampelokipoi, Greece
Investigational Site Number 250001
🇫🇷Paris Cedex 10, France
Investigational Site Number 250031
🇫🇷Poitiers, France
Investigational Site Number 250006
🇫🇷Nantes cedex 01, France
Investigational Site Number 250024
🇫🇷Montpellier, France
Investigational Site Number 276003
🇩🇪Magdeburg, Germany
Investigational Site Number 300002
🇬🇷Ioannina, Greece
Investigational Site Number 348004
🇭🇺Pécs, Hungary
Investigational Site Number 348003
🇭🇺Szeged, Hungary
Investigational Site Number 616005
🇵🇱Gdansk, Poland
Investigational Site Number 642-003
🇷🇴Bucuresti, Romania
Investigational Site Number 756002
🇨🇭Olten, Switzerland
Investigational Site Number 724012
🇪🇸Donostia, Spain
Investigational Site Number 616001
🇵🇱Lodz, Poland
Investigational Site Number 616004
🇵🇱Olsztyn, Poland
Investigational Site Number 642-002
🇷🇴Iasi, Romania
Investigational Site Number 703003
🇸🇰Bratislava, Slovakia
Investigational Site Number 703002
🇸🇰Bratislava, Slovakia
Investigational Site Number 724011
🇪🇸Alicante, Spain
Investigational Site Number 724014
🇪🇸Donostia, Spain
Investigational Site Number 724009
🇪🇸Alicante, Spain
Investigational Site Number 724008
🇪🇸Madrid, Spain
Investigational Site Number 756005
🇨🇭Baden, Switzerland
Investigational Site Number 724003
🇪🇸Córdoba, Spain
Investigational Site Number 724019
🇪🇸Elche, Spain
Investigational Site Number 724020
🇪🇸Inca, Spain
Investigational Site Number 724001
🇪🇸Hospitalet de Llobregat, Spain
Investigational Site Number 724017
🇪🇸Galdakao, Spain
Investigational Site Number 724007
🇪🇸Las Palmas de Gran Canaria, Spain
Investigational Site Number 724005
🇪🇸Málaga, Spain
Investigational Site Number 724006
🇪🇸Valencia, Spain
Investigational Site Number 724002
🇪🇸Santiago de Compostela, Spain
Investigational Site Number 724016
🇪🇸Valencia, Spain
Investigational Site Number 724015
🇪🇸Valladolid, Spain
Investigational Site Number 250017
🇫🇷Nice cedex 1, France
Investigational Site Number 724004
🇪🇸Madrid, Spain
Investigational Site Number 724010
🇪🇸Madrid, Spain
Investigational Site Number 040006
🇦🇹Linz, Austria
Investigational Site Number 040005
🇦🇹Linz, Austria
Investigational Site Number 056008
🇧🇪Arlon, Belgium
Investigational Site Number 056003
🇧🇪Bruxelles, Belgium
Investigational Site Number 056001
🇧🇪Gent, Belgium
Investigational Site Number 056017
🇧🇪Gent, Belgium
Investigational Site Number 124018
🇨🇦Calgary, Canada
Investigational Site Number 124015
🇨🇦Cambridge, Canada
Investigational Site Number 124002
🇨🇦Chicoutimi, Canada
Investigational Site Number 124025
🇨🇦Edmonton, Canada
Investigational Site Number 124017
🇨🇦Halifax, Canada
Investigational Site Number 124013
🇨🇦Hamilton, Canada
Investigational Site Number 124008
🇨🇦London, Canada
Investigational Site Number 124022
🇨🇦Montreal, Canada
Investigational Site Number 124026
🇨🇦Maple Ridge, Canada
Investigational Site Number 124020
🇨🇦Montreal, Canada
Investigational Site Number 124024
🇨🇦Peterborough, Canada
Investigational Site Number 124032
🇨🇦Mount Pearl, Canada
Investigational Site Number 124005
🇨🇦Ottawa, Canada
Investigational Site Number 124003
🇨🇦Quebec, Canada
Investigational Site Number 124007
🇨🇦Sarnia, Canada
Investigational Site Number 124027
🇨🇦Coquitlam, Canada
Investigational Site Number 124030
🇨🇦Smiths Falls, Canada
Investigational Site Number 124001
🇨🇦Sherbrooke, Canada
Investigational Site Number 124019
🇨🇦St-Charles Borromee, Canada
Investigational Site Number 124023
🇨🇦Toronto, Canada
Investigational Site Number 124014
🇨🇦Toronto, Canada
Investigational Site Number 124012
🇨🇦Victoria, Canada
Investigational Site Number 124028
🇨🇦Trois-Rivieres, Canada
Investigational Site Number 124011
🇨🇦Vancouver, Canada
Investigational Site Number 124031
🇨🇦Winnipeg, Canada