Clinical trial NCT03415178: 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
Official title: A Multicenter, Randomized, Open-label, Parallel-group Usability Study of the Commercial 1 mL Alirocumab Auto-injector Device (AI) and the New 2 mL Auto-injector Device (SYDNEY) in High or Very High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolaemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-01-30
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria :

* Participants were in either category A or B (below), and were not adequately controlled with a stable daily dose of atorvastatin (20 mg or 40 mg), or rosuvastatin (10 mg or 20 mg) for at least 4 weeks prior to the screening visit (Week -2), with or without other LMT:

  * A. Participants with heterozygous familial hypercholesterolemia (heFH) (diagnosis based on either genotyping or clinical criteria) OR
  * B. Non-FH Participants at high or very high cardiovascular (CV) risk. High and very high cardiovascular risk participants included participants with coronary heart disease (CHD), non-CHD cardiovascular disease (CVD), and other risk factors.
* Participant willing and able to self-inject for the duration of the study.

Exclusion criteria:

* LDL-C \<70 milligrams per deciliter (mg/dL) (\<1.81 millimoles per litre \[mmol/L\]) at the screening visit.
* Currently taking a daily dose of statin that was not atorvastatin 20 mg or 40 mg, or rosuvastatin 10 mg or 20 mg.
* Not on a stable dose of LMT (including statin) for at least 4 weeks, prior to the screening visit and from screening to randomization.
* Having previously used any device for the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor administration, or having participated in any clinical trial for a PCSK9 inhibitor.
* Fasting serum Triglyceride (TG) \>400 mg/dL (\>4.52 mmol/L) at the screening visit.

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

Primary outcomes:
measure: Percentage of SYDNEY-Associated Product Technical Complaints (PTCs) (Overall) at the Unsupervised Injections: Single-Arm Period
timeFrame: From Week 4 up to Week 12
measure: Percentage of SYDNEY-Associated Product Technical Complaints (PTCs) (by Type) at the Unsupervised Injections: Single-Arm Period
timeFrame: From Week 4 up to Week 12
Secondary outcomes:
measure: 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
timeFrame: Week 0 (Day 1)
measure: Percentage of Participants With SYDNEY-Associated Product Technical Complaint (PTCs) (Overall and by Type) at the Unsupervised Injections : Single-Arm Period
timeFrame: From Week 4 up to Week 12
measure: Injection Experience Questionnaire at Initial Supervised Injection: Overall Ease of Use Scores: Parallel-Arm Period
timeFrame: Week 0 (Day 1)
measure: Patient Perspective Questionnaire After the Last Injection (at Week 12): Single-Arm Period
timeFrame: At Week 12
measure: Injection-Treatment Acceptance Questionnaire (I-TAQ©) After Last Injection (at Week 12) - Overall Acceptance Scores: Single-Arm Period
timeFrame: At Week 12
measure: Maximum Serum Alirocumab Concentration Observed - Cmax : Parallel-Arm Period
timeFrame: Pre-dose (Week 0) and on Day 7, 14 and 21
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alirocumab : Parallel-Arm Period
timeFrame: Pre-dose (Week 0) and on Day 7, 14 and 21
measure: Area Under the Curve-During the Dosing Interval Tau (AUC [0-tau]) : Parallel-Arm Period
timeFrame: Pre-dose (Week 0) and on Day 7, 14 and 21
measure: Maximum Serum Alirocumab Concentration Observed - Cmax : Single-Arm Period
timeFrame: Pre-dose (Week 4, Week 8 and Week 12) and on Day 7, 14, 21 and 28 days following the last injection
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alirocumab: Single-Arm Period
timeFrame: Pre-dose (Week 4, Week 8 and Week 12) and on Day 7, 14, 21 and 28 days following the last injection
measure: Area Under the Curve-During the Dosing Interval Tau (AUC [0-tau]) : Single-Arm Period
timeFrame: Pre-dose (Week 4, Week 8 and Week 12) and on Day 7, 14, 21 and 28 days following the last injection
measure: Free Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Parallel-Arm Period
timeFrame: Week 4
measure: Free Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Single-Arm Period
timeFrame: Week 16
measure: Total Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Parallel-Arm Period
timeFrame: Week 4
measure: Total Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Concentrations : Single-Arm Period
timeFrame: Week 16
measure: Number of Participants With Treatment-Emergent Anti-Alirocumab Antibodies (ADA) Positive Response: Parallel-Arm Period
timeFrame: Up to Week 4
measure: Number of Participants With Treatment-Emergent Anti-Alirocumab Antibodies (ADA) Positive Response According to ADA Status During Parallel-Arm Period: Single Arm Period
timeFrame: Week 16
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 4: Parallel-Arm Period
timeFrame: From Baseline to Week 4
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 8, 12, 16: Single-Arm Period
timeFrame: From Baseline to Weeks 8, 12, and 16
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Investigational Site Number 8400024
state: California
city: Jacksonville
country: United States
facility: Investigational Site Number 8400007
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 8400017
state: Florida
city: Ponte Vedra
country: United States
facility: Investigational Site Number 8400013
state: Florida
city: Wellington
country: United States
facility: Investigational Site Number 8400014
state: Florida
city: West Des Moines
country: United States
facility: Investigational Site Number 8400001
state: Iowa
city: Topeka
country: United States
facility: Investigational Site Number 8400019
state: Kansas
city: Cincinnati
country: United States
facility: Investigational Site Number 8400006
state: Ohio
city: Cincinnati
country: United States
facility: Investigational Site Number 8400010
state: Ohio
city: Summerville
country: United States
facility: Investigational Site Number 8400022
state: South Carolina
city: Amarillo
country: United States
facility: Investigational Site Number 8400026
state: Texas
city: Richmond
country: United States
facility: Investigational Site Number 8400005
state: Virginia
city: Manitowoc
country: United States
facility: Investigational Site Number 8400027
state: Wisconsin
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.