Study to Evaluate the Safety, PK, and Pharmacodynamics of LIB003

Hypercholesterolemia Clinical Trial

— LIB003SAD  

Official title:

Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of LIB003 in Healthy Subjects With Hypercholesterolemia on Diet or Statin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03545438
• Other study ID #: LIB003-001
• Status: Completed
• Phase: Phase 1
• Start date: October 30, 2017
• Est. completion date: June 30, 2018

Study information

• Verified date: July 2018
• Source: LIB Therapeutics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized, double-blind, placebo-controlled, single ascending dose study in nine (9) separate and sequential dose cohorts (7 SC and 2 IV cohorts) to assess the safety and tolerability, pharmacokinetics and pharmacodynamics of LIB003 in subjects with moderately elevated LDL-C levels.

Description:

After meeting eligibility criteria within each cohort subjects will be randomized to receive a single dose of LIB003. Seven (7) cohorts will receive LIB003 escalating doses of LIB003, or placebo, by SC injection and 2 cohorts LIB003 or placebo by IV infusion. Dose escalation will be based on the assessment of safety and tolerability data. All cohorts will each first enroll a sentinel group of subjects who will receive LIB003 or placebo in a double-blind fashion with the remaining subjects in that cohort only to be dosed after the safety data on day 4 from the sentinel subjects has been assessed and deemed safe.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: June 30, 2018
• Est. primary completion date: May 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Men and women who are >/=18 and </=70 years of age. Female subjects must be of non-childbearing potential.

• LDL-C >/=100 mg/dL who are either not on a lipid-lowering therapy or who are on stable statin therapy.

• Body mass index (BMI) >18 and <38 kg/m2

• Mild hypertensives on a stable dose of no more than one antihypertensive drug

Exclusion Criteria:

• History of any prior or concomitant clinical condition or acute and/or unstable systemic disease compromising subject inclusion

• Systolic blood pressure <90 mmHg or >160 mmHg or diastolic blood pressure <50 or >100 mmHg at screening

• Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C virus antibody

• Abnormal liver function test at Screening (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >2 × the upper limit of normal [ULN]

• Estimated glomerular filtration rate <60 mL/min/1.73 m2 at screening, as determined by the CKD-EPI Equation

• History of prescription drug abuse, illicit drug use (including marijuana), or alcohol abuse

• Unable to spend 4 days in confinement unit

• History of allergy to protein-based biologics including, but not limited to, mAbs and vaccine

• Any other finding which, in the opinion of the Investigator, would compromise the subject's safety or participation in the study

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Biological:
• LIB003
LIB003 or placebo

Locations

Country	Name	City	State
United States	Medpace (MARC/CPU)	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
LIB Therapeutics LLC	Medpace, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence and severity of treatment emergent adverse events (TEAEs)	safety and tolerability will be assessed by the incidence and severity of treatment emergent adverse events	43 days
Secondary	Absolute change in serum unbound (free) proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations over time	Serum free PCSK9 will be measured at baseline and various time points over 43 days	43 days
Secondary	Absolute change in serum total PCSK9 over time	Serum total PCSK9 will be measured at baseline and various time points over 43 days	43 days
Secondary	Percent change in Low Density Lipoprotein cholesterol (LDL-C) over time	Serum LDL-C will be measured at baseline and various time points over 43 days to derive percent change	43 days
Secondary	Percent change in Apolipoprotein B (Apo B) over time	Serum Apo B will be measured at baseline and various time points over 43 days to derive percent change	43 days
Secondary	Changes in serum LIB003 concentrations over time	serum LIB003 will be measured at various time points to derive AUC (area under curve)	43 days
Secondary	Presence of anti LIB003 antibodies (ADAs)	Measurement of ADAs will be done at baseline and various intervals after LIB003 administration	43 days