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

LIB Therapeutics

Status and phase: Completed; Phase 1

Conditions: Hypercholesterolemia

Treatments: Biological: LIB003

Study type: Interventional

Funder types: Industry

Identifiers

NCT03545438

LIB003-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 63 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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63 participants in 9 patient groups, including a placebo group

cohort 1

Placebo Comparator group

Description:

LIB003 dose 1 SC

Treatment:

Biological: LIB003

cohort 2

Placebo Comparator group

Description:

LIB003 dose 2 SC

Treatment:

Biological: LIB003

cohort 3

Placebo Comparator group

Description:

LIB003 dose 4 SC

Treatment:

Biological: LIB003

cohort 4

Placebo Comparator group

Description:

LIB003 dose 4 SC

Treatment:

Biological: LIB003

cohort 5

Placebo Comparator group

Description:

LIB003 dose 5 SC

Treatment:

Biological: LIB003

cohort 6

Placebo Comparator group

Description:

LIB003 dose 4 IV

Treatment:

Biological: LIB003

cohort 7

Placebo Comparator group

Description:

LIB003 dose 5 IV

Treatment:

Biological: LIB003

cohort 8

Placebo Comparator group

Description:

LIB003 dose 3 SC - statin treated

Treatment:

Biological: LIB003

cohort 9

Placebo Comparator group

Description:

LIB003 dose 4 SC - statin treated

Treatment:

Biological: LIB003