Philadelphia, Pennsylvania 19104

  • Hypercholesterolemia, Familial

Purpose:

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.


Study summary:

Subjects enrolled in the R1500-CL-1331 clinical trial (NCT0226595) will participate in a study visit before and after administration of the ANGPTL3 inhibitor REGN1500, evinacumab) for the evaluation of its effect on lipoprotein kinetics.


Criteria:

Eligibility criteria: -Eligibility will be made based on the data collected at the screening visit of the R1500-CL-1331 protocol. Subjects must meet all inclusion/exclusion criteria for eligibility of that study to be eligible to participate in this sub-study. Below is the eligibility criteria for R1500-CL-1331. Inclusion: - Men and women 18 years or older at the time of the screening visit - Diagnosis of HoFH by one of the following: 1. Documented mutation or mutations in both LDLR alleles 2. Documented presence of homozygous or compound heterozygous mutations in Apo B and/or PCSK9 3. 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 Exclusion: - 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: 1. have a CD4 count greater than 350c/mL; 2. have an undetectable viral load for at least 12 months prior to screening; 3. have no opportunistic infections or active tuberculosis for at least 12 months prior to screening; 4. are not receiving prophylaxis for opportunistic infections; and have been on stable antiretroviral therapy for at least 12 months prior to screening - Use of another investigational drug or therapy within 30 days or at least 5 half-lives (whichever is longer) prior to screening visit (week -2). Includes patients who were involved in a prior clinical trial and are not sure of their treatment assignment. - Previous participation in any clinical trial of REGN1500 - Conditions/situation such as: 1. Any clinically significant abnormality identified at the time of screening that, in the judgement of the investigator or any subinvestigator, would preclude safe completion of the study or constrain endpoints assessment; eg. major systemic diseases, patients with short life expectancy 2. Patient considered by the investigator or any subinvestigator as inappropriate for this study for any reason, eg: deemed unable to meet specific protocol requirements, such as scheduled visits. Deemed unable to tolerate injections as per the patient or the investigator. Investigator or any subinvestigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol, etc. Presence of any other conditions (eg, geographic or social), either actual or anticipated, that the investigator feels would restrict or limit the patient's participation for the duration of the study - Laboratory findings during screening period: 1. Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody 2. Positive serum beta-human chorionic gonadotropin or urine pregnancy test in women of childbearing potential 3. Triglycerides greater than 400 mg/dL ( >3.95 mmol/L) (1 repeat lab is allowed) 4. Estimated glomerular filtration rate <30 mL/min/1.73m^2 according to 4-variable Modification of Diet in Renal Disease Study equation (calculated by central lab) 5. Alanine amintransferase (ALT) or aspartate aminotransferase (AST) >3 x the upper limit of normal (ULN) (1 repeat lab is allowed) 6. Creatine phosphokinase (CPK) >3 x ULN (1 repeat lab is allowed) - Known hypersensitivity to monoclonal antibody therapeutics - History of hypersensitivity reaction to doxycycline or similar compound - Pregnant or breast-feeding women - Sexually active men, or women of childbearing potential, who are unwilling to utilize adequate contraception for at least 6 months after the last dose of study drug.


Study is Available At:


Original ID:

1331-Kin


NCT ID:

NCT04722068


Secondary ID:


Study Acronym:


Brief Title:

Regeneron 1331 Kinetics Sub-Study HoFH


Official Title:

A Kinetic Study Investigating Lipoprotein Metabolism Before and After the Administration of REGN1500, an ANGPTL3 Inhibitor, in Patients With Homozygous Familial Hypercholesterolemia. A Sub-study for Subjects Enrolled in the R1500-CL-1331 Clinical Trial


Overall Status:

Completed


Study Phase:

N/A


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Pennsylvania


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

4


Enrollment Type:

Actual


Overall Contact Information

Official Name:Marina Cuchel, MD, PhD
Principal Investigator
University of Pennsylvania

Study Dates

Start Date:October 7, 2016
Completion Date:January 1, 2021
Completion Type:Actual
Primary Completion Date:November 30, 2016
Primary Completion Type:Actual
Verification Date:May 2021
Last Changed Date:May 14, 2021
First Received Date:January 12, 2021

Study Outcomes

Outcome Type:Primary Outcome
Measure:Production rate (PR) of lipoproteins mg/kg/day
Time Frame:completion of study, average of 8 weeks
Safety Issues:False
Description: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.
Outcome Type:Primary Outcome
Measure:Fractional catabolic rate (FCR) pools/day
Time Frame:completion of study, average of 8 weeks
Safety Issues:False
Description: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.

Study Interventions

Intervention Type:Other
Name:Kinetics test
Description:Subjects will participate in two study visits to evaluate lipoprotein kinetics before and after administration of evinacumab.
Arm Name:Volunteers with known HoFH and particpated in R150

Study Arms

Study Arm Type:Experimental
Arm Name:Volunteers with known HoFH and particpated in R1500-CL-1331 clinical trial

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Pennsylvania
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Regeneron Pharmaceuticals

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: July 27, 2021

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


This study is not currently recruiting Study Participants. The form below is not enabled.