Usability Study of the Commercial Auto-injector Device and the New Auto-injector Device (SYDNEY) in Patients With High or Very High CV Risk With Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy
- Conditions
- Hypercholesterolaemia
- Interventions
- Device: Current auto-injector device (AI)Device: New auto-injector device (SYDNEY)
- Registration Number
- NCT03415178
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To collect real-use (usability) data assessing the robustness and user interaction of the new alirocumab auto-injector device (which is referred to as SYDNEY), in unsupervised settings.
Secondary Objective:
Device-related:
* To collect real-use (usability) data assessing the robustness and user interaction of SYDNEY and the current alirocumab auto-injector device (which is referred to as AI) in supervised settings.
Pharmacokinetics:
* To compare alirocumab pharmacokinetics (PK) administered using SYDNEY and AI.
* To evaluate alirocumab PK administered using SYDNEY.
Anti-drug antibodies:
* To evaluate the development of anti-drug (alirocumab) antibodies (ADA).
Efficacy/pharmacodynamics:
* To compare the percent and absolute change in low-density lipoprotein cholesterol (LDL-C) using SYDNEY and AI.
* To evaluate the percent and absolute change in LDL-C using SYDNEY.
Safety:
* To evaluate the safety and tolerability of alirocumab using both SYDNEY and AI.
- Detailed Description
Total study duration per participant was expected to be up to 18 weeks, with up to 2 weeks of screening period and 16 weeks of study treatment period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 69
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description New Auto-injector Device (SYDNEY) Alirocumab SAR236553 Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using new auto-injector device (SYDNEY), on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, same treatment (Alirocumab 300 mg) with the same device (SYDNEY) was self-administered, (unsupervised) Q4W until Week 16 in the single arm treatment period added to LMT. Duration of single arm treatment period was 12 weeks, i.e. from Week 4 to 16. Auto-Injector Device (AI) Current auto-injector device (AI) Alirocumab 300 milligram (mg) subcutaneous (SC) injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, participants switched to other arm of SYDNEY device to receive Alirocumab 300 mg, self- administered (unsupervised) using new auto-injector device (SYDNEY) every 4 weeks (Q4W) from Week 4 until Week 16 in the single arm treatment period added to lipid modifying therapy (LMT). Auto-Injector Device (AI) Alirocumab SAR236553 Alirocumab 300 milligram (mg) subcutaneous (SC) injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, participants switched to other arm of SYDNEY device to receive Alirocumab 300 mg, self- administered (unsupervised) using new auto-injector device (SYDNEY) every 4 weeks (Q4W) from Week 4 until Week 16 in the single arm treatment period added to lipid modifying therapy (LMT). New Auto-injector Device (SYDNEY) New auto-injector device (SYDNEY) Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using new auto-injector device (SYDNEY), on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, same treatment (Alirocumab 300 mg) with the same device (SYDNEY) was self-administered, (unsupervised) Q4W until Week 16 in the single arm treatment period added to LMT. Duration of single arm treatment period was 12 weeks, i.e. from Week 4 to 16. Auto-Injector Device (AI) Rosuvastatin Alirocumab 300 milligram (mg) subcutaneous (SC) injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, participants switched to other arm of SYDNEY device to receive Alirocumab 300 mg, self- administered (unsupervised) using new auto-injector device (SYDNEY) every 4 weeks (Q4W) from Week 4 until Week 16 in the single arm treatment period added to lipid modifying therapy (LMT). Auto-Injector Device (AI) Atorvastatin Alirocumab 300 milligram (mg) subcutaneous (SC) injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, participants switched to other arm of SYDNEY device to receive Alirocumab 300 mg, self- administered (unsupervised) using new auto-injector device (SYDNEY) every 4 weeks (Q4W) from Week 4 until Week 16 in the single arm treatment period added to lipid modifying therapy (LMT). New Auto-injector Device (SYDNEY) Atorvastatin Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using new auto-injector device (SYDNEY), on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, same treatment (Alirocumab 300 mg) with the same device (SYDNEY) was self-administered, (unsupervised) Q4W until Week 16 in the single arm treatment period added to LMT. Duration of single arm treatment period was 12 weeks, i.e. from Week 4 to 16. New Auto-injector Device (SYDNEY) Rosuvastatin Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using new auto-injector device (SYDNEY), on-site under supervision in the parallel arm treatment period of 4 weeks. From Week 4, same treatment (Alirocumab 300 mg) with the same device (SYDNEY) was self-administered, (unsupervised) Q4W until Week 16 in the single arm treatment period added to LMT. Duration of single arm treatment period was 12 weeks, i.e. from Week 4 to 16.
- Primary Outcome Measures
Name Time Method Percentage of SYDNEY-Associated Product Technical Complaints (PTCs) (Overall) at the Unsupervised Injections: Single-Arm Period From Week 4 up to Week 12 SYDNEY-associated PTC was defined as any complaint reported on the participant complaint form that triggered an investigation by the device department and was categorized as either device-related, participant-related, or undetermined whether or not associated with an adverse event (AE). Overall category included total of all 3 types of PTCs. The percentage of SYDNEY-associated PTCs was calculated as: Number of PTCs / Number of unsupervised injections\*100. The confidence interval (CI) was calculated using the Wilson score method.
Percentage of SYDNEY-Associated Product Technical Complaints (PTCs) (by Type) at the Unsupervised Injections: Single-Arm Period From Week 4 up to Week 12 SYDNEY-associated PTC was defined as any complaint reported on the participant complaint form that triggered an investigation by the device department and was categorized as either device-related, participant-related, or undetermined whether or not associated with an AE.
- Secondary Outcome Measures
Name Time Method Maximum Serum Alirocumab Concentration Observed - Cmax : Single-Arm Period Pre-dose (Week 4, Week 8 and Week 12) and on Day 7, 14, 21 and 28 days following the last injection Cmax: maximum serum concentration observed.
Area Under the Curve-During the Dosing Interval Tau (AUC [0-tau]) : Single-Arm Period Pre-dose (Week 4, Week 8 and Week 12) and on Day 7, 14, 21 and 28 days following the last injection AUC0-tau: area under the serum concentration versus time curve calculated using the trapezoidal method during a dosage interval tau, where dosing interval was 4 weeks.
Free Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Parallel-Arm Period Week 4 Free PCSK9 concentrations below the lower limit of quantification (LLOQ) were set to zero.
Number of Participants With Treatment-Emergent Anti-Alirocumab Antibodies (ADA) Positive Response: Parallel-Arm Period Up to Week 4 Anti-drug (alirocumab) antibodies samples were analyzed using a validated electrochemiluminescence assay. Number of participants with positive ADA during treatment emergent adverse event (TEAE) period (time from the first IMP injection to the day before the second IMP injection for participants entered into the single arm period or to 70 days after the first IMP injection, whichever comes first) was determined. Treatment-emergent positive ADA response defined as 1) participants with no ADA positive response at baseline but with any positive response in the post-baseline period or 2) participants with a positive ADA response at baseline and at least a 4- fold increase in titer in the post-baseline period.
Number of Participants With Treatment-Emergent Anti-Alirocumab Antibodies (ADA) Positive Response According to ADA Status During Parallel-Arm Period: Single Arm Period Week 16 Number of participants with positive ADA during the TEAE period (time from the second IMP injection up to the day of last IMP injection + 70 days) were determined. Treatment-emergent positive ADA response in Single-arm period defined as 1) participants with no ADA positive response in the Parallel-arm period but with any positive response in the Single-arm period or 2) participants with a positive ADA response at baseline, with less than 4-fold increase in titer in the Parallel-arm period (Pre-existing ADA in Parallel-arm period) and at least a 4- fold increase in titer in the Single-arm period.
Percentage of Participants With SYDNEY-Associated Product Technical Complaint (PTCs) (Overall and by Type) at the Unsupervised Injections : Single-Arm Period From Week 4 up to Week 12 A PTC was defined as any complaint reported on the participant complaint form that triggered an investigation by the device department and was categorized as either device-related, participant-related, or undetermined, whether or not associated with an AE. Percentage of Participants With a SYDNEY-associated PTC (for the reporting arm "Alirocumab from new auto-injector device \[SYDNEY\])" are reported.
Free Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Single-Arm Period Week 16 Free PCSK9 concentrations below the LLOQ were set to zero.
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 8, 12, 16: Single-Arm Period From Baseline to Weeks 8, 12, and 16 Injection-Treatment Acceptance Questionnaire (I-TAQ©) After Last Injection (at Week 12) - Overall Acceptance Scores: Single-Arm Period At Week 12 The I-TAQ© was a well-established and validated questionnaire to measure participant satisfaction with SC auto-injector devices. The I-TAQ© (completed by the participant after the last injection) was self-administered questionnaire administered to participants in order to measure their acceptance of the injection. The overall acceptance is one of the five domain scores. The overall acceptance score ranged from 0 to 100, with 0 indicating low acceptance and 100 indicating high acceptance.
Maximum Serum Alirocumab Concentration Observed - Cmax : Parallel-Arm Period Pre-dose (Week 0) and on Day 7, 14 and 21 Cmax: Maximum serum concentration observed.
Total Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Parallel-Arm Period Week 4 Total PCSK9 concentrations below the LLOQ were set to zero.
Total Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Single-Arm Period Week 16 Total PCSK9 concentrations below the LLOQ were set to zero.
Patient Perspective Questionnaire After the Last Injection (at Week 12): Single-Arm Period At Week 12 The aim of the patient perspective questionnaire (completed by the participant after the last injection) was to generate data to support an understanding of the participant experience and satisfaction associated with use of the large volume SYDNEY to administer the 300 mg dose. The questionnaire consisted of 6 questions about level of satisfaction with various aspects of the SYDNEY; with response to each question ranging from 1 (very dissatisfied) to 10 (very satisfied), with higher scores indicated more satisfaction. An additional question (confidence that Sydney device was used correctly) regarding confidence of use of SYDNEY device in the study was evaluated on a scale of 10; where 1 being not at all confident, to 10 being very confident, higher scores indicated more confidence.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alirocumab: Single-Arm Period Pre-dose (Week 4, Week 8 and Week 12) and on Day 7, 14, 21 and 28 days following the last injection Tmax: Time to reach Cmax.
Percentage of Participants With a SYDNEY or Current Auto-Injector (AI)-Associated Product Technical Complaint (PTCs) (Overall and by Type) at the Supervised Injections on Week 0 (Day 1): Parallel-Arm Period Week 0 (Day 1) A PTC was defined as any complaint reported on the participant complaint form that triggered an investigation by the device department and was categorized as either device-related, participant-related, or undetermined, whether or not associated with an AE. Percentage of participants With a SYDNEY-associated PTC (for the reporting arm "Alirocumab from new auto-injector device") or Current AI-Associated PTCs (for the reporting arm "alirocumab from AI device") are reported.
Injection Experience Questionnaire at Initial Supervised Injection: Overall Ease of Use Scores: Parallel-Arm Period Week 0 (Day 1) Participants were given an injection experience questionnaire to complete after the self-injection they administered using SYDNEY device or current AI device on Day 1, for assessment of user experience and overall ease-of-use. The questionnaire included 9 questions about specific aspects of using the device. Overall ease of use was the 9th question, response of which ranged from 1 (very difficult) to 10 (very easy), with higher score indicated more ease of use.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alirocumab : Parallel-Arm Period Pre-dose (Week 0) and on Day 7, 14 and 21 Tmax: Time to reach Cmax.
Area Under the Curve-During the Dosing Interval Tau (AUC [0-tau]) : Parallel-Arm Period Pre-dose (Week 0) and on Day 7, 14 and 21 AUC0-tau: area under the serum concentration versus time curve calculated using the trapezoidal method during a dosage interval tau, where dosing interval was 4 weeks.
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 4: Parallel-Arm Period From Baseline to Week 4 Adjusted least square means and standard errors at Week 4 were calculated from analyses of covariance (ANCOVA) model with the fixed categorical effect of treatment group (SYDNEY, AI), as well as the continuous fixed covariate of baseline LDL-C value.
Trial Locations
- Locations (13)
Investigational Site Number 8400022
🇺🇸Summerville, South Carolina, United States
Investigational Site Number 8400017
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 8400013
🇺🇸Ponte Vedra, Florida, United States
Investigational Site Number 8400010
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 8400027
🇺🇸Manitowoc, Wisconsin, United States
Investigational Site Number 8400024
🇺🇸Los Angeles, California, United States
Investigational Site Number 8400026
🇺🇸Amarillo, Texas, United States
Investigational Site Number 8400014
🇺🇸Wellington, Florida, United States
Investigational Site Number 8400006
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 8400001
🇺🇸West Des Moines, Iowa, United States
Investigational Site Number 8400019
🇺🇸Topeka, Kansas, United States
Investigational Site Number 8400007
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 8400005
🇺🇸Richmond, Virginia, United States