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

NCT03415178 | Completed Phase 3 Results FDA Drug FDA Device

• 2 other identifiers: MSC14864U1111-1186-3466
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 13

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.

Conditions

Hypercholesterolaemia

Outcome Measures

Primary Outcomes (2)

• 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.

  From Week 4 up to Week 12

• 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.

  From Week 4 up to Week 12

Secondary Outcomes (19)

• 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)

• 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

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

  Week 0 (Day 1)

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

  At Week 12

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

  At Week 12

Study Arms (2)

Auto-Injector Device (AI)

EXPERIMENTAL

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

New Auto-injector Device (SYDNEY)

EXPERIMENTAL

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

Alirocumab SAR236553 DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Auto-Injector Device (AI); New Auto-injector Device (SYDNEY)

Current auto-injector device (AI) DEVICE

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

Auto-Injector Device (AI)

New auto-injector device (SYDNEY) DEVICE

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

New Auto-injector Device (SYDNEY)

Atorvastatin DRUG

Pharmaceutical form:tablet Route of administration: oral

Auto-Injector Device (AI); New Auto-injector Device (SYDNEY)

Rosuvastatin DRUG

Pharmaceutical form:tablet Route of administration: oral

Auto-Injector Device (AI); New Auto-injector Device (SYDNEY)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (13)

Investigational Site Number 8400024

Los Angeles, California, 90057, United States

Location

Investigational Site Number 8400007

Jacksonville, Florida, 32216, United States

Location

Investigational Site Number 8400017

Jacksonville, Florida, 32223, United States

Location

Investigational Site Number 8400013

Ponte Vedra, Florida, 32081, United States

Location

Investigational Site Number 8400014

Wellington, Florida, 33449, United States

Location

Investigational Site Number 8400001

West Des Moines, Iowa, 50266, United States

Location

Investigational Site Number 8400019

Topeka, Kansas, 66606, United States

Location

Investigational Site Number 8400006

Cincinnati, Ohio, 45201, United States

Location

Investigational Site Number 8400010

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 8400022

Summerville, South Carolina, 29485, United States

Location

Investigational Site Number 8400026

Amarillo, Texas, 79106, United States

Location

Investigational Site Number 8400005

Richmond, Virginia, 23227, United States

Location

Investigational Site Number 8400027

Manitowoc, Wisconsin, 54220, United States

Location

Related Publications (1)

• 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.

  PMID: 31879033 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab; Atorvastatin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: January 30, 2018
• Study Start: March 29, 2018
• Primary Completion: August 9, 2018
• Study Completion: August 9, 2018
• Last Updated: September 9, 2019
• Results First Posted: September 9, 2019

Record last verified: 2019-09

Locations

US (13)