NCT04189484

Pharmacodynamic Biomarkers to Support Biosimilar Development: PCSK9 Inhibitors

Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 2: PCSK9 Inhibitors - Alirocumab and Evolocumab

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 72 (actual)
• Sponsor: Food and Drug Administration (FDA) · Federal
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies. This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab and alirocumab ) or placebo.

Detailed description

This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab, two monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies. This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab or alirocumab) or placebo. Evolocumab doses are 21, 35, 70, and 140 mg. Reslizumab doses are 15, 25, 50, and 100 mg . Each arm will include 8 subjects (4 male and 4 female). Subjects will be admitted for treatment on day -1 and receive a single dose of study drug or placebo on day 1. Depending on the treatment arm, subjects will remain in confinement for one week and continue follow-up through day 42, 56, or 84. Blood samples (approximately 5 mL per sample) will be collected for determination of plasma concentrations for study drug. Additional blood samples will be collected for lipid analysis and determination of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) (5 mL per sample; pharmacodynamic measure) and exploratory proteomics analyses (5 mL per sample). Safety evaluations will include adverse event (AE) monitoring, vital sign measurements, and physical examinations. All AEs reported by the subject or observed by the investigator or clinical research unit (CRU) staff will be recorded. Any AE reported after the informed consent is signed and before study drug application will be recorded as medical history.

Conditions

• Healthy Subjects
• Pharmacokinetics
• Pharmacodynamics

Interventions

Type	Name	Description
BIOLOGICAL	Evolocumab	Evolocumab 21 mg administered SC
BIOLOGICAL	Evolocumab	Evolocumab 35 mg administered SC
BIOLOGICAL	Evolocumab	Evolocumab 70 mg administered SC
BIOLOGICAL	Evolocumab	Evolocumab 140 mg administered SC
BIOLOGICAL	Alirocumab	Alirocumab 15 mg administered SC
BIOLOGICAL	Alirocumab	Alirocumab 25 mg administered SC
BIOLOGICAL	Alirocumab	Alirocumab 50 mg administered SC
BIOLOGICAL	Alirocumab	Alirocumab 100 mg administered SC
BIOLOGICAL	Placebo	Placebo administered SC

Timeline

• Start date: 2020-01-07
• Primary completion: 2021-04-07
• Completion: 2021-04-07
• First posted: 2019-12-06
• Last updated: 2024-04-22
• Results posted: 2024-04-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study