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

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• Hypercholesterolemia 1,267

Hypercholesterolemia

1,267 studies on the registry are indexed under Hypercholesterolemia; 105 are open to participants now.

This study's enrollment of 69 is below the median of 100 across 1,015 interventional studies indexed under Hypercholesterolemia.

Lead sponsor

Sanofi is the lead sponsor of 1,547 studies on the registry; 88 are open to participants now.

Of its 204 completed or terminated interventional studies of FDA-regulated products, 122 (60%) have results posted.

Study arms

• Experimental
  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).

  Drug: Alirocumab SAR236553 · Device: Current auto-injector device (AI) · Drug: Atorvastatin · Drug: Rosuvastatin

• Experimental
  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.

  Drug: Alirocumab SAR236553 · Device: New auto-injector device (SYDNEY) · Drug: Atorvastatin · Drug: Rosuvastatin

Interventions

• DrugAlirocumab SAR236553

  Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

• DeviceCurrent auto-injector device (AI)

  Pharmaceutical form: Route of administration: Subcutaneous self-administration of alirocumab

• DeviceNew auto-injector device (SYDNEY)

  Pharmaceutical form: Route of administration: Subcutaneous self-administration of alirocumab

• DrugAtorvastatin

  Pharmaceutical form:tablet Route of administration: oral

• DrugRosuvastatin

  Pharmaceutical form:tablet Route of administration: oral

Primary outcomes

1. Percentage of SYDNEY-Associated Product Technical Complaints (PTCs) (Overall) at the Unsupervised Injections: Single-Arm Period

   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.

   Time frame: From Week 4 up to Week 12

2. Percentage of SYDNEY-Associated Product Technical Complaints (PTCs) (by Type) at the Unsupervised Injections: Single-Arm Period

   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.

   Time frame: From Week 4 up to Week 12

Secondary outcomes

1. 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

   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.

   Time frame: Week 0 (Day 1)

2. Percentage of Participants With SYDNEY-Associated Product Technical Complaint (PTCs) (Overall and by Type) at the Unsupervised Injections : Single-Arm Period

   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.

   Time frame: From Week 4 up to Week 12

3. Injection Experience Questionnaire at Initial Supervised Injection: Overall Ease of Use Scores: Parallel-Arm Period

   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 frame: Week 0 (Day 1)

4. Patient Perspective Questionnaire After the Last Injection (at Week 12): Single-Arm Period

   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 frame: At Week 12

5. Injection-Treatment Acceptance Questionnaire (I-TAQ©) After Last Injection (at Week 12) - Overall Acceptance Scores: Single-Arm Period

   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.

   Time frame: At Week 12

6. Maximum Serum Alirocumab Concentration Observed - Cmax : Parallel-Arm Period

   Cmax: Maximum serum concentration observed.

   Time frame: Pre-dose (Week 0) and on Day 7, 14 and 21

7. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alirocumab : Parallel-Arm Period

   Tmax: Time to reach Cmax.

   Time frame: Pre-dose (Week 0) and on Day 7, 14 and 21

8. Area Under the Curve-During the Dosing Interval Tau (AUC [0-tau]) : Parallel-Arm Period

   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.

   Time frame: Pre-dose (Week 0) and on Day 7, 14 and 21

9. Maximum Serum Alirocumab Concentration Observed - Cmax : Single-Arm Period

   Cmax: maximum serum concentration observed.

   Time frame: Pre-dose (Week 4, Week 8 and Week 12) and on Day 7, 14, 21 and 28 days following the last injection

10. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alirocumab: Single-Arm Period

    Tmax: Time to reach Cmax.

    Time frame: Pre-dose (Week 4, Week 8 and Week 12) and on Day 7, 14, 21 and 28 days following the last injection

11. Area Under the Curve-During the Dosing Interval Tau (AUC [0-tau]) : Single-Arm Period

    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.

    Time frame: Pre-dose (Week 4, Week 8 and Week 12) and on Day 7, 14, 21 and 28 days following the last injection

12. Free Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Parallel-Arm Period

    Free PCSK9 concentrations below the lower limit of quantification (LLOQ) were set to zero.

    Time frame: Week 4

13. Free Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Single-Arm Period

    Free PCSK9 concentrations below the LLOQ were set to zero.

    Time frame: Week 16

14. Total Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Parallel-Arm Period

    Total PCSK9 concentrations below the LLOQ were set to zero.

    Time frame: Week 4

15. Total Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Single-Arm Period

    Total PCSK9 concentrations below the LLOQ were set to zero.

    Time frame: Week 16

16. Number of Participants With Treatment-Emergent Anti-Alirocumab Antibodies (ADA) Positive Response: Parallel-Arm Period

    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.

    Time frame: Up to Week 4

17. Number of Participants With Treatment-Emergent Anti-Alirocumab Antibodies (ADA) Positive Response According to ADA Status During Parallel-Arm Period: Single Arm Period

    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.

    Time frame: Week 16

18. Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 4: Parallel-Arm Period

    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.

    Time frame: From Baseline to Week 4

19. Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 8, 12, 16: Single-Arm Period

    Time frame: From Baseline to Weeks 8, 12, and 16

Baseline characteristics

Publications

• Frias JP, Koren MJ, Loizeau V, Merino-Trigo A, Louie MJ, Raudenbush MA, Batsu I. The SYDNEY Device Study: A Multicenter, Randomized, Open-label Usability Study of a 2-mL Alirocumab Autoinjector Device. Clin Ther. 2020 Jan;42(1):94-107.e5. doi: 10.1016/j.clinthera.2019.11.008. Epub 2019 Dec 24. PubMed 31879033 ↗

Study documents

• Study protocol · Nov 20, 2017
• Statistical analysis plan · Mar 27, 2018

Documents are hosted by the registry — open the source record to download them.