Study to Evaluate the Safety, PK, and Pharmacodynamics of LIB003 (LIB003SAD)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Biological: LIB003

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Medpace (MARC/CPU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: cohort 1; LIB003 dose 1 SC	Biological: LIB003; LIB003 or placebo
Placebo Comparator: cohort 2; LIB003 dose 2 SC	Biological: LIB003; LIB003 or placebo
Placebo Comparator: cohort 3; LIB003 dose 4 SC	Biological: LIB003; LIB003 or placebo
Placebo Comparator: cohort 4; LIB003 dose 4 SC	Biological: LIB003; LIB003 or placebo
Placebo Comparator: cohort 5; LIB003 dose 5 SC	Biological: LIB003; LIB003 or placebo
Placebo Comparator: cohort 6; LIB003 dose 4 IV	Biological: LIB003; LIB003 or placebo
Placebo Comparator: cohort 7; LIB003 dose 5 IV	Biological: LIB003; LIB003 or placebo
Placebo Comparator: cohort 8; LIB003 dose 3 SC - statin treated	Biological: LIB003; LIB003 or placebo
Placebo Comparator: cohort 9; LIB003 dose 4 SC - statin treated	Biological: LIB003; LIB003 or placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Changes in serum LIB003 concentrations over time	serum LIB003 will be measured at various time points to derive AUC (area under curve)	43 days
Presence of anti LIB003 antibodies (ADAs)	Measurement of ADAs will be done at baseline and various intervals after LIB003 administration	43 days

Collaborators and Investigators

• Sponsor: LIB Therapeutics LLC
• Collaborators: Medpace, Inc.
• Investigators: Principal Investigator: Traci A Turner, MD, Medpace Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2017
• Primary Completion (Actual): May 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: April 19, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): June 4, 2018

Study Record Updates

• Last Update Posted (Actual): July 27, 2018
• Last Update Submitted That Met QC Criteria: July 26, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: LIB003-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No