Clinical trial NCT02023879: Phase III Study To Evaluate Alirocumab in Patients With Hypercholesterolemia Not Treated With a Statin (ODYSSEY CHOICE II)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy and Safety of Alirocumab in Patients With Primary Hypercholesterolemia Not Treated With a Statin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2013-12-30
Enrollment: 233
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A double-blind treatment period of 24 weeks (3 parallel arms) followed by an open-label extension period (single arm)
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by a regimen of Alirocumab including a starting dose of 150 mg every 4 weeks (Q4W) as add-on to non-statin lipid modifying background therapy or as monotherapy in comparison with placebo in participants with primary hypercholesterolemia not treated with a statin.

Secondary Objective:

* To evaluate the effects on other lipid parameters of Alirocumab 150 mg Q4W versus placebo.
* To evaluate the safety and tolerability of Alirocumab 150 mg Q4W.

Alirocumab 75 mg Q2W was added as a calibrator arm.

Detailed description: The core study duration was approximately 35 weeks per participant (screening: 3 weeks, double-blind treatment period: 24 weeks; follow-up: 8 weeks). Participants who successfully completed the treatment period had the possibility to participate in an optional open-label treatment period with Alirocumab 150 mg Q4W until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first.

Eligibility criteria: Inclusion criteria:

Participants with primary hypercholesterolemia (heterozygous familial hypercholesterolemia \[heFH\] or non-FH) not adequately controlled with their non-statin LMT (either ezetimibe or fenofibrate) or diet alone.

Exclusion criteria:

* LDL-C \<70 mg/dL (1.81 mmol/L) at screening for statin intolerant participants at very high cardiovascular (CV) risk;
* LDL-C \<100 mg/dL (\<2.59 mmol/L) at screening for statin intolerant participants at high or moderate CV risk or, participants not fulfilling the statin intolerant definition at moderate CV risk;
* LDL-C ≥160 mg/dL (≥4.1 mmol/L) at screening for participants receiving diet only or, participants not fulfilling the statin intolerant definition at moderate CV risk and receiving a non-statin LMT.

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

Primary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total-C at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
Other outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase
timeFrame: Baseline, Week 32, 36, 48, 72, 96, 120, 144 and Week 168
Locations:
city: Beverly Hills
country: United States
facility: Investigational Site Number 840703
state: California
city: Atlantis
country: United States
facility: Investigational Site Number 840704
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840708
state: Florida
city: Sarasota
country: United States
facility: Investigational Site Number 840701
state: Florida
city: Fall River
country: United States
facility: Investigational Site Number 840706
state: Massachusetts
city: Saint Louis
country: United States
facility: Investigational Site Number 840705
state: Missouri
city: Durham
country: United States
facility: Investigational Site Number 840707
state: North Carolina
city: Summerville
country: United States
facility: Investigational Site Number 840702
state: South Carolina
city: Ashford
country: Australia
facility: Investigational Site Number 036703
city: Perth
country: Australia
facility: Investigational Site Number 036702
city: Woolloongabba
country: Australia
facility: Investigational Site Number 036701
city: Antwerpen
country: Belgium
facility: Investigational Site Number 056702
city: Haine-Saint-Paul
country: Belgium
facility: Investigational Site Number 056703
city: Leuven
country: Belgium
facility: Investigational Site Number 056701
city: Chicoutimi
country: Canada
facility: Investigational Site Number 124703
city: Quebec
country: Canada
facility: Investigational Site Number 124701
city: Sherbrooke
country: Canada
facility: Investigational Site Number 124704
city: Toronto
country: Canada
facility: Investigational Site Number 124706
city: Vancouver
country: Canada
facility: Investigational Site Number 124702
city: Victoria
country: Canada
facility: Investigational Site Number 124705
city: Aarhus
country: Denmark
facility: Investigational Site Number 208703
city: Esbjerg
country: Denmark
facility: Investigational Site Number 208702
city: Glostrup
country: Denmark
facility: Investigational Site Number 208701
city: Hvidovre
country: Denmark
facility: Investigational Site Number 208704
city: Køge
country: Denmark
facility: Investigational Site Number 208705
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 528701
city: Den Helder
country: Netherlands
facility: Investigational Site Number 528708
city: Hoogeveen
country: Netherlands
facility: Investigational Site Number 528702
city: Hoorn
country: Netherlands
facility: Investigational Site Number 528703
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528706
city: Sneek
country: Netherlands
facility: Investigational Site Number 528709
city: Utrecht
country: Netherlands
facility: Investigational Site Number 528704
city: Venlo
country: Netherlands
facility: Investigational Site Number 528707
city: Auckland
country: New Zealand
facility: Investigational Site Number 554702
city: Christchurch
country: New Zealand
facility: Investigational Site Number 554701
city: A Coruna
country: Spain
facility: Investigational Site Number 724703
city: Barcelona
country: Spain
facility: Investigational Site Number 724707
city: Barcelona
country: Spain
facility: Investigational Site Number 724710
city: Córdoba
country: Spain
facility: Investigational Site Number 724702
city: Granada
country: Spain
facility: Investigational Site Number 724705
city: Sant Joan Despí
country: Spain
facility: Investigational Site Number 724709
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number 724706
city: Zaragoza
country: Spain
facility: Investigational Site Number 724701
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Stroes E, Guyton JR, Lepor N, Civeira F, Gaudet D, Watts GF, Baccara-Dinet MT, Lecorps G, Manvelian G, Farnier M; ODYSSEY CHOICE II Investigators. Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study. J Am Heart Assoc. 2016 Sep 13;5(9):e003421. doi: 10.1161/JAHA.116.003421.