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

Primary Purpose

Hypercholesterolemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

LIB003

About this trial

This is an interventional treatment trial for Hypercholesterolemia

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts 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

Sites / Locations

Medpace (MARC/CPU)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Placebo Comparator

Arm Label

cohort 1

cohort 2

cohort 3

cohort 4

cohort 5

cohort 6

cohort 7

cohort 8

cohort 9

Arm Description

LIB003 dose 1 SC

LIB003 dose 2 SC

LIB003 dose 4 SC

LIB003 dose 5 SC

LIB003 dose 4 IV

LIB003 dose 5 IV

LIB003 dose 3 SC - statin treated

LIB003 dose 4 SC - statin treated

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Absolute change in serum total PCSK9 over time

Serum total PCSK9 will be measured at baseline and various time points over 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

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

Changes in serum LIB003 concentrations over time

serum LIB003 will be measured at various time points to derive AUC (area under curve)

Presence of anti LIB003 antibodies (ADAs)

Measurement of ADAs will be done at baseline and various intervals after LIB003 administration

Full Information

NCT ID

NCT03545438

First Posted

April 19, 2018

Last Updated

July 26, 2018

Sponsor

LIB Therapeutics LLC

Collaborators

Medpace, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03545438

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

October 30, 2017 (Actual)

Primary Completion Date

May 30, 2018 (Actual)

Study Completion Date

June 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

LIB Therapeutics LLC

Collaborators

Medpace, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

single ascending dose with placebo controll

Masking

ParticipantCare ProviderInvestigator

Masking Description

Within each dosing cohort randomization is performed according to a computer-generated randomization scheme. Other than the study drug prepared by an unblinded pharmacist and administered by unblinded nurses who will be instructed not to discuss randomized treatment assignments and have no other role in the study, all study staff and PI, along with the subjects are blinded as to treatment.

Allocation

Randomized

Enrollment

63 (Actual)

8. Arms, Groups, and Interventions

Arm Title

cohort 1

Arm Type

Placebo Comparator

Arm Description

LIB003 dose 1 SC

Arm Title

cohort 2

Arm Type

Placebo Comparator

Arm Description

LIB003 dose 2 SC

Arm Title

cohort 3

Arm Type

Placebo Comparator

Arm Description

LIB003 dose 4 SC

Arm Title

cohort 4

Arm Type

Placebo Comparator

Arm Description

LIB003 dose 4 SC

Arm Title

cohort 5

Arm Type

Placebo Comparator

Arm Description

LIB003 dose 5 SC

Arm Title

cohort 6

Arm Type

Placebo Comparator

Arm Description

LIB003 dose 4 IV

Arm Title

cohort 7

Arm Type

Placebo Comparator

Arm Description

LIB003 dose 5 IV

Arm Title

cohort 8

Arm Type

Placebo Comparator

Arm Description

LIB003 dose 3 SC - statin treated

Arm Title

cohort 9

Arm Type

Placebo Comparator

Arm Description

LIB003 dose 4 SC - statin treated

Intervention Type

Biological

Intervention Name(s)

LIB003

Intervention Description

LIB003 or placebo

Primary Outcome Measure Information:

Title

The incidence and severity of treatment emergent adverse events (TEAEs)

Description

safety and tolerability will be assessed by the incidence and severity of treatment emergent adverse events

Time Frame

43 days

Secondary Outcome Measure Information:

Title

Absolute change in serum unbound (free) proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations over time

Description

Serum free PCSK9 will be measured at baseline and various time points over 43 days

Time Frame

43 days

Title

Absolute change in serum total PCSK9 over time

Description

Serum total PCSK9 will be measured at baseline and various time points over 43 days

Time Frame

43 days

Title

Percent change in Low Density Lipoprotein cholesterol (LDL-C) over time

Description

Serum LDL-C will be measured at baseline and various time points over 43 days to derive percent change

Time Frame

43 days

Title

Percent change in Apolipoprotein B (Apo B) over time

Description

Serum Apo B will be measured at baseline and various time points over 43 days to derive percent change

Time Frame

43 days

Title

Changes in serum LIB003 concentrations over time

Description

serum LIB003 will be measured at various time points to derive AUC (area under curve)

Time Frame

43 days

Title

Presence of anti LIB003 antibodies (ADAs)

Description

Measurement of ADAs will be done at baseline and various intervals after LIB003 administration

Time Frame

43 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Traci A Turner, MD

Organizational Affiliation

Medpace Clinical Research

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medpace (MARC/CPU)

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45227

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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