Clinical trial NCT03545438: Study to Evaluate the Safety, PK, and Pharmacodynamics of LIB003
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
Lead sponsor: LIB Therapeutics LLC
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
First posted: 2018-06-04
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: single ascending dose with placebo controll
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The incidence and severity of treatment emergent adverse events (TEAEs)
timeFrame: 43 days
Secondary outcomes:
measure: Absolute change in serum unbound (free) proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations over time
timeFrame: 43 days
measure: Absolute change in serum total PCSK9 over time
timeFrame: 43 days
measure: Percent change in Low Density Lipoprotein cholesterol (LDL-C) over time
timeFrame: 43 days
measure: Percent change in Apolipoprotein B (Apo B) over time
timeFrame: 43 days
measure: Changes in serum LIB003 concentrations over time
timeFrame: 43 days
measure: Presence of anti LIB003 antibodies (ADAs)
timeFrame: 43 days
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Medpace (MARC/CPU)
state: Ohio
Study officials:
affiliation: Medpace Clinical Research
name: Traci A Turner, MD
role: PRINCIPAL_INVESTIGATOR
References: