Safety, Tolerability, and Effect of Alirocumab in High Cardiovascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-modifying Therapies (ODYSSEY APPRISE)

NCT02476006 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: LPS142452015-000620-28U1111-1163-0984
• Study Type: interventional
• Target: 998
• Locations: 15 countries
• Sites: 150

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).

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

  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.

  From first injection of investigational medicinal product (IMP) up to 2 weeks after last dose of study drug (Week 120)

Secondary Outcomes (10)

• Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

  Baseline, Week 12

• Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12

  At Week 12

• Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 12

  At Week 12

• 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

• Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12

  Baseline, Week 12

Study Arms (1)

Alirocumab

EXPERIMENTAL

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.

Drug: ALIROCUMAB SAR236553 (REGN727); Drug: placebo (for injection training only); Drug: ezetimibe; Drug: atorvastatin; Drug: rosuvastatin; Drug: simvastatin

Interventions

ALIROCUMAB SAR236553 (REGN727) DRUG

Pharmaceutical form:solution Route of administration: subcutaneous

Also known as: Praluent®

Alirocumab

placebo (for injection training only) DRUG

Pharmaceutical form:solution Route of administration: subcutaneous

Alirocumab

ezetimibe DRUG

Pharmaceutical form:capsule Route of administration: oral

Alirocumab

atorvastatin DRUG

Pharmaceutical form:tablet Route of administration: oral

Alirocumab

rosuvastatin DRUG

Pharmaceutical form:tablet Route of administration: oral

Alirocumab

simvastatin DRUG

Pharmaceutical form:tablet Route of administration: oral

Alirocumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Either A, B, C, D, or E below and not adequately controlled with a maximally tolerated dose of statin with or without other LMTs, all at stable doses for at least 4 weeks prior to the screening visit (Week-3):
• A. Participants suffering from heterozygous familial hypercholesterolemia (heFH) with LDL-C concentrations greater than or equal to (\>=)160 mg/dL (4.14 millimoles per liter \[mmol/L\]) despite treatment.
• B. Participants suffering from heFH with LDL-C concentrations \>=130 mg/dL (3.36 mmol/L) despite treatment and two or more CV risk factors among this list:
• LDL-C greater than (\>) 250 milligrams per deciliter (mg/dL) (6.46 mmol/L) at the time of the familial hypercholesterolemia (FH) diagnosis (before treatment).
• Family history of premature-onset coronary heart disease (CHD; first-degree male relative with onset before age 55 years; first-degree female relative with onset before age 65 years).
• Metabolic syndrome.
• HDL-C less than (\<) 40 mg/dL (1.03 mmol/L).
• Hypertension (blood pressure \>140/90 mmHg or drug treatment).
• Lipoprotein a (Lp\[a\]) \>=50 mg/dL (1.78 µmol/L).
• Tendon xanthoma.
• C. Participants suffering from heFH with LDL-C concentrations \>=130 mg/dL (3.36 mmol/L) despite treatment and one of the following characteristics:
• Established CHD or other cardiovascular disease (CVD; history of acute myocardial infarction, ischemic stroke, peripheral arterial disease, coronary or peripheral arterial revascularization, stable or unstable angina, transient ischemic attack, carotid artery stenosis \>=50 percent (%), or aortic abdominal aneurysm).
• Drug-treated type 2 diabetes mellitus or type 1 with target organ damage.
• Family history of first- or second-degree relative with very premature onset CHD (first- or second-degree male relative with onset before age 45; first- or second-degree female relative with onset before age 55).
• D. Non-FH participants suffering from established CHD or other CVD (history of acute myocardial infarction (MI), ischemic stroke, peripheral arterial disease, coronary or peripheral arterial revascularization, stable or unstable angina, transient ischemic attack, carotid artery stenosis \>=50%, or aortic abdominal aneurysm) and with LDL-C concentrations \>=130 mg/dL (3.36 mmol/L).

You may not qualify if:

• Not on a stable dose of LMT (including statin) for at least 4 weeks prior to the screening visit (Week -3) and from screening to enrollment.
• Use of a fibrate other than fenofibrate within 4 weeks of the screening visit (Week-3) or between screening and enrollment.
• Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except for participants on simvastatin 80 mg for more than one year, who were eligible).
• Use of statin other than simvastatin, atorvastatin, or rosuvastatin prior to the screening visit (Week-3) or between screening and enrollment, except when there was a documented reason for intolerance to the above mentioned potent statins (in which case the use of a different statin was allowed).
• Fasting serum TG \>400 mg/dL (\>4.52 mmol/L) at the screening visit (Week -3). Uncontrolled hypertension (\>180 mmHg systolic and/or \>110 mmHg diastolic at randomization visit).
• New York Heart Association Class III or IV congestive heart failure persisting despite treatment.
• History of hemorrhagic stroke. Liver transaminases \>3 times the upper limit of normal. Laboratory evidence of current hepatitis B or C infection. Creatine kinase \>3 times the upper limit of normal. Estimated glomerular filtration rate \<30 mL/min/1.73 m\^2. Pregnant or breastfeeding woman or with childbearing potential without appropriate contraception.
• Male participant with a female partner of childbearing potential not protected by a highly-effective method(s) of birth control.
• Participants eligible for enrollment into an ongoing clinical study of alirocumab conducted at the same investigational site.
• Hypersensitivity to alirocumab or any of the excipients.
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (153)

Investigational Site Number 040001

Graz, Austria

Location

Investigational Site Number 040008

Innsbruck, 6020, Austria

Location

Investigational Site Number 040005

Linz, 4010, Austria

Location

Investigational Site Number 040006

Linz, 4021, Austria

Location

Investigational Site Number 040003

Vienna, 1030, Austria

Location

Investigational Site Number 040002

Vienna, 1090, Austria

Location

Investigational Site Number 040004

Vienna, 1130, Austria

Location

Investigational Site Number 040007

Vienna, 1160, Austria

Location

Investigational Site Number 040010

Vienna, 1160, Austria

Location

Investigational Site Number 056005

Aalst, 9300, Belgium

Location

Investigational Site Number 056018

Antwerp, 2020, Belgium

Location

Investigational Site Number 056008

Arlon, 6700, Belgium

Location

Investigational Site Number 056013

Bruges, 8000, Belgium

Location

Investigational Site Number 056010

Brussels, 1090, Belgium

Location

Investigational Site Number 056003

Brussels, 1200, Belgium

Location

Investigational Site Number 056006

Charleroi, 6000, Belgium

Location

Investigational Site Number 056007

Edegem, 2650, Belgium

Location

Investigational Site Number 056019

Genk, 3600, Belgium

Location

Investigational Site Number 056001

Ghent, 9000, Belgium

Location

Investigational Site Number 056017

Ghent, 9000, Belgium

Location

Investigational Site Number 056002

Haine-Saint-Paul, 7100, Belgium

Location

Investigational Site Number 056015

Kortrijk, 8500, Belgium

Location

Investigational Site Number 056009

La Louvière, 7100, Belgium

Location

Investigational Site Number 056004

Leuven, 3000, Belgium

Location

Investigational Site Number 056014

Liège, 4000, Belgium

Location

Investigational Site Number 056011

Overpelt, 3900, Belgium

Location

Investigational Site Number 056016

Roeselare, 8800, Belgium

Location

Investigational Site Number 124018

Calgary, T2E7C5, Canada

Location

Investigational Site Number 124015

Cambridge, N1R6V6, Canada

Location

Investigational Site Number 124002

Chicoutimi, G7H7K9, Canada

Location

Investigational Site Number 124027

Coquitlam, V3K3P4, Canada

Location

Investigational Site Number 124025

Edmonton, T6G2B7, Canada

Location

Investigational Site Number 124017

Halifax, B3H1V7, Canada

Location

Investigational Site Number 124013

Hamilton, L8L 2X2, Canada

Location

Investigational Site Number 124008

London, N6A 4L6, Canada

Location

Investigational Site Number 124026

Maple Ridge, V2X5Z6, Canada

Location

Investigational Site Number 124020

Montreal, H2W1R7, Canada

Location

Investigational Site Number 124022

Montreal, H4A3J1, Canada

Location

Investigational Site Number 124032

Mount Pearl, A1N1W7, Canada

Location

Investigational Site Number 124005

Ottawa, K1Y4W7, Canada

Location

Investigational Site Number 124024

Peterborough, K9J0B2, Canada

Location

Investigational Site Number 124003

Québec, G1V4W2, Canada

Location

Investigational Site Number 124019

Saint-Charles-Borromée, J6E6J2, Canada

Location

Investigational Site Number 124007

Sarnia, N7T 4X3, Canada

Location

Investigational Site Number 124001

Sherbrooke, J1H 5N4, Canada

Location

Investigational Site Number 124030

Smiths Falls, K7A4W8, Canada

Location

Investigational Site Number 124023

Toronto, M4N3M5, Canada

Location

Investigational Site Number 124014

Toronto, M5B1W8, Canada

Location

Investigational Site Number 124028

Trois-Rivières, Canada

Location

Investigational Site Number 124011

Vancouver, V5Y3W2, Canada

Location

Investigational Site Number 124012

Victoria, V8T5G4, Canada

Location

Investigational Site Number 124031

Winnipeg, R2H2A6, Canada

Location

Investigational Site Number 124009

Woodstock, N4S5P5, Canada

Location

Investigational Site Number 203004

Brno, 65691, Czechia

Location

Investigational Site Number 203002

Hradec Králové, 50005, Czechia

Location

Investigational Site Number 203001

Prague, 12808, Czechia

Location

Investigational Site Number 203005

Uherské Hradiště, 68601, Czechia

Location

Investigational Site Number 208003

Aalborg, 9000, Denmark

Location

Investigational Site Number 208001

Esbjerg, 6700, Denmark

Location

Investigational Site Number 208002

Roskilde, 4000, Denmark

Location

Investigational Site Number 246003

Turku, 20520, Finland

Location

Investigational Site Number 246001

Varkaus, 78300, Finland

Location

Investigational Site Number 250027

Amiens, 80054, France

Location

Investigational Site Number 250034

Auxerre, 89011, France

Location

Investigational Site Number 250016

Avignon, 84000, France

Location

Investigational Site Number 250021

Bayonne, 64100, France

Location

Investigational Site Number 250030

Bobigny, 93009, France

Location

Investigational Site Number 250045

Bordeaux, 33075, France

Location

Investigational Site Number 250049

Brest, 29610, France

Location

Investigational Site Number 250054

Bron, 69677, France

Location

Investigational Site Number 250015

Caen, 14000, France

Location

Investigational Site Number 250047

Clermont-Ferrand, 63003, France

Location

Investigational Site Number 250013

Corbeil-Essonnes, 91100, France

Location

Investigational Site Number 250032

Coudray, 28630, France

Location

Investigational Site Number 250002

Dijon, 21000, France

Location

Investigational Site Number 250040

Dijon, 21000, France

Location

Investigational Site Number 250012

Grenoble, 38028, France

Location

Investigational Site Number 250038

Grenoble, 38043, France

Location

Investigational Site Number 250033

Jossigny, France

Location

Investigational Site Number 250035

Le Chesnay, 78157, France

Location

Investigational Site Number 250036

Lens, France

Location

Investigational Site Number 250042

Lille, 59000, France

Location

Investigational Site Number 250004

Lille, France

Location

Investigational Site Number 250037

Limoges, 87000, France

Location

Investigational Site Number 250057

Lyon, 69009, France

Location

Investigational Site Number 250028

Marseille, 13385, France

Location

Investigational Site Number 250048

Marseille, 13385, France

Location

Investigational Site Number 250024

Montpellier, 34295, France

Location

Investigational Site Number 250006

Nantes, 44093, France

Location

Investigational Site Number 250022

Nantes, 44277, France

Location

Investigational Site Number 250017

Nice, 06001, France

Location

Investigational Site Number 250039

Nîmes, 30029, France

Location

Investigational Site Number 250014

Paris, 75014, France

Location

Investigational Site Number 250041

Paris, 75014, France

Location

Investigational Site Number 250026

Paris, 75018, France

Location

Investigational Site Number 250044

Paris, 75181, France

Location

Investigational Site Number 250001

Paris, 75475, France

Location

Investigational Site Number 250051

Pessac, 33604, France

Location

Investigational Site Number 250011

Poitiers, 86021, France

Location

Investigational Site Number 250031

Poitiers, 86021, France

Location

Investigational Site Number 250010

Reims, 51092, France

Location

Investigational Site Number 250008

Rennes, France

Location

Investigational Site Number 250018

Rouen, 76000, France

Location

Investigational Site Number 250023

Saint-Mandé, 94160, France

Location

Investigational Site Number 250025

Toulouse, 31059, France

Location

Investigational Site Number 250046

Toulouse, 31076, France

Location

Investigational Site Number 250007

Tours, 37000, France

Location

Investigational Site Number 250019

Vénissieux, 69200, France

Location

Investigational Site Number 250050

Vichy, 03201, France

Location

Investigational Site Number 276001

Berlin, 12559, Germany

Location

Investigational Site Number 276003

Magdeburg, 39120, Germany

Location

Investigational Site Number 300003

Ampelokipoi, 11522, Greece

Location

Investigational Site Number 300002

Ioannina, 45500, Greece

Location

Investigational Site Number 300001

Kallithea, Greece

Location

Investigational Site Number 348001

Budapest, 1125, Hungary

Location

Investigational Site Number 348002

Debrecen, 4032, Hungary

Location

Investigational Site Number 348004

Pécs, Hungary

Location

Investigational Site Number 348003

Szeged, 6725, Hungary

Location

Investigational Site Number 616005

Gdansk, 80-952, Poland

Location

Investigational Site Number 616003

Krakow, 30-082, Poland

Location

Investigational Site Number 616001

Lodz, 90-549, Poland

Location

Investigational Site Number 616004

Olsztyn, 10-045, Poland

Location

Investigational Site Number 616002

Warsaw, 04-628, Poland

Location

Investigational Site Number 642-003

Bucharest, 011461, Romania

Location

Investigational Site Number 642-002

Iași, 700661, Romania

Location

Investigational Site Number 642-001

Timișoara, 300298, Romania

Location

Investigational Site Number 703003

Bratislava, 81108, Slovakia

Location

Investigational Site Number 703002

Bratislava, 83101, Slovakia

Location

Investigational Site Number 703001

Košice, 04011, Slovakia

Location

Investigational Site Number 705001

Maribor, 2000, Slovenia

Location

Investigational Site Number 724009

Alicante, 03010, Spain

Location

Investigational Site Number 724011

Alicante, 3550, Spain

Location

Investigational Site Number 724003

Córdoba, 14004, Spain

Location

Investigational Site Number 724012

Donostia / San Sebastian, 20014, Spain

Location

Investigational Site Number 724014

Donostia / San Sebastian, 20014, Spain

Location

Investigational Site Number 724019

Elche, 03203, Spain

Location

Investigational Site Number 724017

Galdakao, 48960, Spain

Location

Investigational Site Number 724020

Inca, 03700, Spain

Location

Investigational Site Number 724001

L'Hospitalet de Llobregat, 08907, Spain

Location

Investigational Site Number 724007

Las Palmas de Gran Canaria, 35016, Spain

Location

Investigational Site Number 724004

Madrid, 28007, Spain

Location

Investigational Site Number 724008

Madrid, 28034, Spain

Location

Investigational Site Number 724010

Madrid, 28046, Spain

Location

Investigational Site Number 724005

Málaga, 29010, Spain

Location

Investigational Site Number 724002

Santiago de Compostela, 15706, Spain

Location

Investigational Site Number 724006

Valencia, 46010, Spain

Location

Investigational Site Number 724016

Valencia, 46014, Spain

Location

Investigational Site Number 724015

Valladolid, 47011, Spain

Location

Investigational Site Number 756005

Baden, 5404, Switzerland

Location

Investigational Site Number 756002

Olten, 4600, Switzerland

Location

Investigational Site Number 756004

Reinach, 4153, Switzerland

Location

Investigational Site Number 756003

Sankt Gallen, 9007, Switzerland

Location

Investigational Site Number 756001

Zurich, 8032, Switzerland

Location

Related Publications (1)

• Cefalu AB, Garbelotto R, Mombelli G, Pirro M, Rubba P, Arca M, Borghi C, Bonomo K, Gonnelli S, Massaroni K, Tirone G, Averna M; ODYSSEY APPRISE Study Italian Investigators. A subgroup analysis of the ODYSSEY APPRISE study: Safety and efficacy of alirocumab in the Italian cohort. Nutr Metab Cardiovasc Dis. 2022 Nov;32(11):2638-2646. doi: 10.1016/j.numecd.2022.07.020. Epub 2022 Aug 9.

  PMID: 36064689 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab; Ezetimibe; Atorvastatin; Rosuvastatin Calcium; Simvastatin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 19, 2015
• Study Start: June 23, 2015
• Primary Completion: April 12, 2019
• Study Completion: April 12, 2019
• Last Updated: March 28, 2022
• Results First Posted: March 30, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

SL (1); AU (9); CZ (4); GR (3); RO (3); BE (18); DE (2); CA (26); CH (5); DK (3); HU (4); ES (18); PL (5); FR (47); FI (2)