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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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ClinicalTrials.gov Identifier: NCT03415178
Recruitment Status : Completed
First Posted : January 30, 2018
Results First Posted : September 9, 2019
Last Update Posted : September 9, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypercholesterolaemia
Interventions Drug: Alirocumab SAR236553
Device: Current auto-injector device (AI)
Device: New auto-injector device (SYDNEY)
Drug: Atorvastatin
Drug: Rosuvastatin
Enrollment 69
Recruitment Details The study was conducted at 13 centers in the United States. A total of 92 participants were screened on 29-March-2018 with randomization between 05 April 2018 and 12 April 18 of whom 23 were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details Randomization to treatment arms was done centrally using treatment allocation system (Interactive Response Technology) in a 1:1 ratio (alirocumab from auto-injector device [AI] : alirocumab from new auto-injector device [SYDNEY]). A total of 69 participants were randomized.
Arm/Group Title Auto-Injector Device (AI) New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description 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). 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.
Period Title: Parallel-Arm Period (up to Week 4)
Started [1] 34 [1] 35 [1]
Treated 34 33
Completed 34 [2] 33 [3]
Not Completed 0 2
Reason Not Completed
Randomized but not treated             0             2
[1]
Randomized
[2]
33 participants entered in single arm period & 1 participant decided not to enter single arm period.
[3]
32 participants entered in single arm period & 1 participant decided not to enter single arm period.
Period Title: Single Arm Period (up to Week 16)
Started 0 [1] 66 [2]
Completed 0 65
Not Completed 0 1
Reason Not Completed
Adverse Event             0             1
[1]
Out of 34 participants from AI group, 33 participants entered entered in single arm period.
[2]
65 (participants completed period 1) + 1 (randomized to SYDNEY arm but not treated in period 1).
Arm/Group Title Auto-Injector Device (AI) New Auto-injector Device (SYDNEY) Total
Hide Arm/Group Description Alirocumab 300 mg 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) Q4W from Week 4 until Week 16 in the single arm treatment period added to LMT. 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. Total of all reporting groups
Overall Number of Baseline Participants 34 35 69
Hide Baseline Analysis Population Description
Analysis was performed on all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants 35 participants 69 participants
65.1  (8.6) 65.4  (8.1) 65.3  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 35 participants 69 participants
Female
19
  55.9%
9
  25.7%
28
  40.6%
Male
15
  44.1%
26
  74.3%
41
  59.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 35 participants 69 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   5.9%
1
   2.9%
3
   4.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
8
  23.5%
3
   8.6%
11
  15.9%
White
24
  70.6%
31
  88.6%
55
  79.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Low-Density Lipoprotein Cholesterol (LDL-C)   [1] 
Mean (Standard Deviation)
Unit of measure:  Milligram per deciliter (mg/dL)
Number Analyzed 34 participants 34 participants 68 participants
98.6  (24.3) 91.0  (15.0) 94.8  (20.4)
[1]
Measure Analysis Population Description:

Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/5]).

Here, "Number analyzed" signifies number of participants with available data for this baseline measure.

1.Primary Outcome
Title Percentage of SYDNEY-Associated Product Technical Complaints (PTCs) (Overall) at the Unsupervised Injections: Single-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population of the single-arm period which included all randomized participants who continued in the single-arm period and received at least 1 dose or part of a dose of investigational medicinal product (IMP) during this period.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 66
Overall Number of Units Analyzed
Type of Units Analyzed: Number of unsupervised injections
196
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of PTCs
0.5
(0.0 to 3.2)
2.Primary Outcome
Title Percentage of SYDNEY-Associated Product Technical Complaints (PTCs) (by Type) at the Unsupervised Injections: Single-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population of the single-arm period.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 66
Overall Number of Units Analyzed
Type of Units Analyzed: Number of unsupervised injections
196
Measure Type: Number
Unit of Measure: percentage of PTCs
Device-related 0
Participant-related 0.5
Undetermined 0
3.Secondary Outcome
Title 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
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population of the parallel-arm period which included all randomized participants who received at least 1 dose or part of a dose of IMP during this period.
Arm/Group Title Auto-Injector Device (AI) New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT.
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 period of 4 weeks added to LMT.
Overall Number of Participants Analyzed 34 33
Measure Type: Number
Unit of Measure: percentage of participants
Overall 0 0
Type: Device-related 0 0
Type: Participant-related 0 0
Type: Undetermined 0 0
4.Secondary Outcome
Title Percentage of Participants With SYDNEY-Associated Product Technical Complaint (PTCs) (Overall and by Type) at the Unsupervised Injections : Single-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population of the single-arm period.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 66
Measure Type: Number
Unit of Measure: percentage of participants
Overall 1.5
Type: Device-related 0
Type: Participant-related 1.5
Type: Undetermined 0
5.Secondary Outcome
Title Injection Experience Questionnaire at Initial Supervised Injection: Overall Ease of Use Scores: Parallel-Arm Period
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population of the parallel-arm period.
Arm/Group Title Auto-Injector Device (AI) New Auto-injector Device (SYDNEY)
Hide Arm/Group Description:
Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT.
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 period of 4 weeks added to LMT.
Overall Number of Participants Analyzed 34 33
Mean (Standard Deviation)
Unit of Measure: score on a scale
9.9  (0.2) 9.8  (0.5)
6.Secondary Outcome
Title Patient Perspective Questionnaire After the Last Injection (at Week 12): Single-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population of the single-arm period.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 66
Mean (Standard Deviation)
Unit of Measure: score on a scale
Size of the auto-injector 9.7  (0.8)
Ease of holding the auto-injector in hand 9.8  (0.6)
2-step operation:remove cap, press AI against skin 9.9  (0.4)
Length of time it took to complete the injection 9.9  (0.3)
Fact that needle is hidden prior & after injection 10.0  (0.3)
Once monthly injection 10.0  (0.1)
Confidence that Sydney device was used correctly 9.9  (0.4)
7.Secondary Outcome
Title Injection-Treatment Acceptance Questionnaire (I-TAQ©) After Last Injection (at Week 12) - Overall Acceptance Scores: Single-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population of the single-arm period. Here, overall number of participants analyzed = participants who answered the I-TAQ.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 65
Mean (Standard Deviation)
Unit of Measure: score on a scale
93.08  (9.94)
8.Secondary Outcome
Title Maximum Serum Alirocumab Concentration Observed - Cmax : Parallel-Arm Period
Hide Description Cmax: Maximum serum concentration observed.
Time Frame Pre-dose (Week 0) and on Day 7, 14 and 21
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on pharmacokinetics (PK) population of the parallel-arm period which included all randomized participants who received at least 1 dose or part of a dose of IMP and had at least one evaluable blood sample for PK during this period. Here, "Overall number of participants analyzed" = participants evaluable for this PK measure.
Arm/Group Title Auto-Injector Device (AI) New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT.
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 period of 4 weeks added to LMT.
Overall Number of Participants Analyzed 33 31
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
25800  (8430) 26800  (8420)
9.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alirocumab : Parallel-Arm Period
Hide Description Tmax: Time to reach Cmax.
Time Frame Pre-dose (Week 0) and on Day 7, 14 and 21
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population of the parallel-arm period. Here, "Overall number of participants analyzed" = participants evaluable for this PK measure.
Arm/Group Title Auto-Injector Device (AI) New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT.
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 period of 4 weeks added to LMT.
Overall Number of Participants Analyzed 33 31
Median (Full Range)
Unit of Measure: days
7.00
(6.00 to 14.00)
7.00
(6.00 to 7.00)
10.Secondary Outcome
Title Area Under the Curve-During the Dosing Interval Tau (AUC [0-tau]) : Parallel-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population of the parallel-arm period. Here, "Overall number of participants analyzed" = participants evaluable for this PK measure.
Arm/Group Title Auto-Injector Device (AI) New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT.
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 period of 4 weeks added to LMT.
Overall Number of Participants Analyzed 32 31
Mean (Standard Deviation)
Unit of Measure: ng*day/mL
381000  (147000) 414000  (152000)
11.Secondary Outcome
Title Maximum Serum Alirocumab Concentration Observed - Cmax : Single-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population of the single-arm period which included all randomized participants who received at least 1 dose or part of a dose of IMP and had at least one evaluable blood sample for PK during this period. Here, "Overall number of participants analyzed" = participants evaluable for this PK measure.
Arm/Group Title New Auto-injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 64
Mean (Standard Deviation)
Unit of Measure: ng/mL
31900  (13100)
12.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alirocumab: Single-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population of the single-arm period. Here, "Overall number of participants analyzed" = participants evaluable for this PK measure.
Arm/Group Title New Auto-injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 64
Median (Full Range)
Unit of Measure: days
7.00
(3.00 to 11.00)
13.Secondary Outcome
Title Area Under the Curve-During the Dosing Interval Tau (AUC [0-tau]) : Single-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population of the single-arm period. Here, "Overall number of participants analyzed" = participants evaluable for this PK measure.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: ng*day/mL
509000  (264000)
14.Secondary Outcome
Title Free Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Parallel-Arm Period
Hide Description Free PCSK9 concentrations below the lower limit of quantification (LLOQ) were set to zero.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population of the parallel-arm period. Here, "Overall number of participants analyzed" = participants evaluable for this outcome measure.
Arm/Group Title Auto-Injector Device (AI) New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT.
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 period of 4 weeks added to LMT.
Overall Number of Participants Analyzed 33 32
Mean (Standard Deviation)
Unit of Measure: ng/mL
90.1  (110.5) 78.3  (103.1)
15.Secondary Outcome
Title Free Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Single-Arm Period
Hide Description Free PCSK9 concentrations below the LLOQ were set to zero.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population of the single-arm period. Here, "Overall number of participants analyzed" = participants evaluable for this PK measure.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 65
Mean (Standard Deviation)
Unit of Measure: ng/mL
88.9  (116.4)
16.Secondary Outcome
Title Total Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Parallel-Arm Period
Hide Description Total PCSK9 concentrations below the LLOQ were set to zero.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population of the parallel-arm period. Here, "Overall number of participants analyzed" = participants evaluable for this outcome measure.
Arm/Group Title Auto-Injector Device (AI) New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT.
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 period of 4 weeks added to LMT.
Overall Number of Participants Analyzed 33 32
Mean (Standard Deviation)
Unit of Measure: ng/mL
3329.7  (1147.7) 3370.0  (916.6)
17.Secondary Outcome
Title Total Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Single-Arm Period
Hide Description Total PCSK9 concentrations below the LLOQ were set to zero.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population of the single-arm period. Here, "Overall number of participants analyzed" = participants evaluable for this PK measure.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 65
Mean (Standard Deviation)
Unit of Measure: ng/mL
3481.4  (1290.1)
18.Secondary Outcome
Title Number of Participants With Treatment-Emergent Anti-Alirocumab Antibodies (ADA) Positive Response: Parallel-Arm Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ADA population of the parallel-arm period which included all randomized participants who received at least 1 or part of a dose of IMP during this period with baseline and at least one post-baseline available ADA sample during this period. All participants were analyzed according to the AI device they actually received.
Arm/Group Title Auto-Injector Device (AI) New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT.
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 period of 4 weeks added to LMT.
Overall Number of Participants Analyzed 32 32
Measure Type: Count of Participants
Unit of Measure: Participants
2
   6.3%
1
   3.1%
19.Secondary Outcome
Title Number of Participants With Treatment-Emergent Anti-Alirocumab Antibodies (ADA) Positive Response According to ADA Status During Parallel-Arm Period: Single Arm Period
Hide Description 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
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Hide Analysis Population Description
Analysis was performed on ADA population of single-arm period which included all randomized participants who received at least 1 or partial dose of IMP during this period with available baseline and at least 1 post-baseline ADA sample available during this period. Here, "Number analyzed" = participants with ADA assessed at specified time point.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 64
Measure Type: Count of Participants
Unit of Measure: Participants
Pre-existing ADA Number Analyzed 1 participants
0
   0.0%
Negative ADA status Number Analyzed 60 participants
2
   3.3%
Treatment-emergent ADA positive Number Analyzed 3 participants
0
   0.0%
20.Secondary Outcome
Title Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 4: Parallel-Arm Period
Hide Description 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
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Hide Analysis Population Description
Analysis was performed on modified intent-to-treat (mITT) population of the parallel-arm period which included all randomized participants who received at least 1 dose or part of a dose of IMP during this period and who had an evaluable baseline and an on-treatment LDL-C value within Week 4 analysis window and before second injection, if any.
Arm/Group Title Auto-Injector Device (AI) New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT.
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 period of 4 weeks added to LMT.
Overall Number of Participants Analyzed 32 31
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-51.2  (4.4) -66.2  (4.4)
21.Secondary Outcome
Title Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 8, 12, 16: Single-Arm Period
Hide Description [Not Specified]
Time Frame From Baseline to Weeks 8, 12, and 16
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Hide Analysis Population Description
mITT population of single-arm period included all randomized participants who continued in single-arm period & received at least 1 dose/part of a dose of IMP & who had an evaluable baseline & at least 1 on-treatment LDL-C value within analysis windows (Week 8 to 16). Number analyzed=participants with available data at specified time-point.
Arm/Group Title New Auto-Injector Device (SYDNEY)
Hide Arm/Group Description:
All participants who were randomized to Alirocumab 300 mg SC injection using either AI device or SYDNEY in the parallel arm treatment period of 4 weeks and continued in single arm period, Alirocumab 300 mg self-administered (unsupervised) SC injection using SYDNEY device Q4W at Week 4, 8 and 12 in single arm period added to LMT. Duration of single arm treatment period was 12 weeks (i.e. from Week 4 to 16).
Overall Number of Participants Analyzed 66
Mean (Standard Deviation)
Unit of Measure: percent change
Week 8 Number Analyzed 66 participants
-53.737  (32.641)
Week 12 Number Analyzed 65 participants
-58.610  (25.068)
Week 16 Number Analyzed 64 participants
-56.991  (25.930)
Time Frame All AEs were collected from signature of the informed consent form up to final visit (Week 16) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported AEs are treatment emergent that is AEs that developed/worsened during 'the treatment emergent period' (the time from first IMP injection to the second IMP injection for participants entering into the single-arm period, or to 70 days after first IMP injection, whichever comes first [Parallel arm period] or the time from the second IMP injection up to the day of last IMP injection + 70 days [Single arm period]). Analysis was performed on safety population.
 
Arm/Group Title Auto-Injector Device (AI) (Parallel Arm Period) New Auto-Injector Device (Parallel-arm Period) New Auto-Injector Device (Single-arm Period)
Hide Arm/Group Description Alirocumab 300 mg SC injection on Week 0 (Day 1), self-administered using AI device, on-site under supervision in the parallel arm period of 4 weeks added to LMT. 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 period of 4 weeks added to LMT. 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 at Week 4, 8 and 12 in the single arm treatment period. Duration of single arm treatment period was 12 weeks, i.e. from Week 4 to 16 added to LMT.
All-Cause Mortality
Auto-Injector Device (AI) (Parallel Arm Period) New Auto-Injector Device (Parallel-arm Period) New Auto-Injector Device (Single-arm Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/34 (0.00%)      0/33 (0.00%)      0/66 (0.00%)    
Hide Serious Adverse Events
Auto-Injector Device (AI) (Parallel Arm Period) New Auto-Injector Device (Parallel-arm Period) New Auto-Injector Device (Single-arm Period)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/34 (2.94%)      1/33 (3.03%)      2/66 (3.03%)    
Cardiac disorders       
Acute Myocardial Infarction  1  1/34 (2.94%)  1 0/33 (0.00%)  0 0/66 (0.00%)  0
Coronary Artery Disease  1  0/34 (0.00%)  0 0/33 (0.00%)  0 1/66 (1.52%)  1
Investigations       
Alanine Aminotransferase Increased  1  0/34 (0.00%)  0 1/33 (3.03%)  1 0/66 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Chondritis  1  0/34 (0.00%)  0 0/33 (0.00%)  0 1/66 (1.52%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Auto-Injector Device (AI) (Parallel Arm Period) New Auto-Injector Device (Parallel-arm Period) New Auto-Injector Device (Single-arm Period)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/34 (5.88%)      5/33 (15.15%)      8/66 (12.12%)    
Infections and infestations       
Upper Respiratory Tract Infection  1  0/34 (0.00%)  0 3/33 (9.09%)  3 0/66 (0.00%)  0
Urinary Tract Infection  1  0/34 (0.00%)  0 0/33 (0.00%)  0 4/66 (6.06%)  4
Injury, poisoning and procedural complications       
Contusion  1  2/34 (5.88%)  2 1/33 (3.03%)  1 1/66 (1.52%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/34 (0.00%)  0 2/33 (6.06%)  2 3/66 (4.55%)  3
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi aventis recherche & développement
Phone: 800-633-1610 ext 1#
EMail: Contact-US@sanofi.com
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03415178    
Other Study ID Numbers: MSC14864
U1111-1186-3466 ( Other Identifier: UTN )
First Submitted: January 4, 2018
First Posted: January 30, 2018
Results First Submitted: August 8, 2019
Results First Posted: September 9, 2019
Last Update Posted: September 9, 2019