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 040008
🇦🇹Innsbruck, Austria
Investigational Site Number 040005
🇦🇹Linz, Austria
Investigational Site Number 040006
🇦🇹Linz, Austria
Investigational Site Number 040003
🇦🇹Wien, Austria
Investigational Site Number 040002
🇦🇹Wien, Austria
Investigational Site Number 040004
🇦🇹Wien, Austria
Investigational Site Number 040007
🇦🇹Wien, Austria
Investigational Site Number 040010
🇦🇹Wien, Austria
Investigational Site Number 056005
🇧🇪Aalst, Belgium
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