Regeneron 1331 Kinetics Sub-Study HoFH

NCT04722068 | Completed

• 1 other identifier: 1331-Kin
• Study Type: interventional
• Target: 4
• Locations: 2 countries
• Sites: 2

Brief Summary

To evaluate the lipoprotein kinetics of subjects enrolled in the R1500-CL-1331 clinical trial (NCT02265952) to assess the mechanism by which the evinacumab may affect lipid levels in HoFH subjects.

Conditions

Hypercholesterolemia, Familial

Keywords

Lipid metabolism; Homozygous Familial Hypercholesterolemia; Evinacumab

Outcome Measures

Primary Outcomes (2)

• Fractional catabolic rate (FCR) pools/day

  First visit to be performed prior to first evinacumab administration; second visit to be performed approximately 4-6 weeks after evinacumab i.v. administration. About 8 weeks between the 2 visits.

  completion of study, average of 8 weeks

• Production rate (PR) of lipoproteins mg/kg/day

  First visit to be performed prior to first evinacumab administration; second visit to be performed approximately 4-6 weeks after evinacumab i.v. administration. About 8 weeks between the 2 visits.

  completion of study, average of 8 weeks

Study Arms (1)

Volunteers with known HoFH and particpated in R1500-CL-1331 clinical trial

EXPERIMENTAL

Other: Kinetics test

Interventions

Kinetics test OTHER

Subjects will participate in two study visits to evaluate lipoprotein kinetics before and after administration of evinacumab.

Volunteers with known HoFH and particpated in R1500-CL-1331 clinical trial

Eligibility Criteria

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

You may not qualify if:

• Men and women 18 years or older at the time of the screening visit
• Diagnosis of HoFH by one of the following:
• Documented mutation or mutations in both LDLR alleles
• Documented presence of homozygous or compound heterozygous mutations in Apo B and/or PCSK9
• Documented skin fibroblast LDLR activity \<20% of normal
• Willing to consistently maintain his/her usual diet for the duration of the study
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent
• Background medical LMT (if applicable) that has not been stable for at least 4 weeks (6 weeks for fibrates) prior to the screening visit (week -2) (unless participating in the run-in period to stabilize)
• Having undergone lipid apheresis within 4 weeks prior to the screening visit (week -2) (unless participating in the run-in period to wash out)
• Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins. Note: Patients on thyroid replacement therapy can be included if the dosage of thyroxine has been stable for at least 12 weeks prior to screening visit (week -2)
• Use of systemic corticosteroids, unless used as replacement therapy for pituitary/adrenal disease with a stable regiment for at least 6 weeks prior to the screening visit (week -2) Note: Topical, intra-articular, nasal, inhaled, and ophthalmic steroid therapies are not considered as "systemic" and are allowed
• History of a myocardial infarction, unstable angina leading to hospitalization, coronary bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit (week -2)
• Known history of HIV and a CD4 count less than 350c/mL Note: Patients with a history of HIV can be included, as long as they:
• have a CD4 count greater than 350c/mL;

Sponsors & Collaborators

• University of Pennsylvania: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (2)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Department of Vascular Medicine Amsterdam UMC

Amsterdam, AZ, 1105, Netherlands

Location

Related Publications (1)

• Reeskamp LF, Millar JS, Wu L, Jansen H, van Harskamp D, Schierbeek H, Gipe DA, Rader DJ, Dallinga-Thie GM, Hovingh GK, Cuchel M. ANGPTL3 Inhibition With Evinacumab Results in Faster Clearance of IDL and LDL apoB in Patients With Homozygous Familial Hypercholesterolemia-Brief Report. Arterioscler Thromb Vasc Biol. 2021 May 5;41(5):1753-1759. doi: 10.1161/ATVBAHA.120.315204. Epub 2021 Mar 11.

  PMID: 33691480 DERIVED

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Marina Cuchel, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 25, 2021
• Study Start: October 7, 2016
• Primary Completion: November 30, 2016
• Study Completion: January 1, 2021
• Last Updated: May 17, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); NL (1)