NCT03844191

Brief Summary

This study is designed to assess tolerability of the weight-adjusted dose of RUC-4 (mg/kg) required to achieve 80% or more inhibition of the initial slope of platelet aggregation to 20 µM ADP by Light Transmission Aggregometry (LTA) within 15 minutes of SC administration of RUC-4 with return toward baseline values within 4 hours in healthy volunteers and subjects on aspirin with stable coronary artery disease (CAD). In the Dose Expansion Part, VerifyNow PRUTest will be used to measure platelet aggregation in addition to LTA. Since the goal of RUC-4 therapy is to achieve maximal antiplatelet therapy as rapidly as possible, first the tolerability of the weight-adjusted dose (mg/kg) that inhibits ADP-induced platelet aggregation by 80% or more in 5 of 6 healthy volunteers will be identified. A similar dose escalation will be subsequently performed in subjects with CAD who are taking aspirin. To facilitate administration using a single weight-adjusted (mg/kg) dose for a defined group of subjects weighing between 55 and 120 kg, the study will also evaluate the safety and biologic effect on platelet aggregation of the weight adjusted (mg/kg) dose when administered to subjects with weights at either end of this range.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Feb 2019

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 13, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 18, 2019

Completed
Same day until next milestone

Study Start

First participant enrolled

February 18, 2019

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2019

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
Last Updated

August 27, 2024

Status Verified

August 1, 2024

Enrollment Period

9 months

First QC Date

February 13, 2019

Last Update Submit

August 23, 2024

Conditions

Coronary Disease

Outcome Measures

Primary Outcomes (10)

  • Platelet Inhibition

    inhibition of platelet aggregation

    5 minutes

  • Platelet inhibition

    inhibition of platelet aggregation

    15 min

  • Platelet inhibition

    inhibition of platelet aggregation

    30 min

  • Platelet inhibition

    inhibition of platelet aggregation

    60 min

  • Platelet inhibition

    inhibition of platelet aggregation

    90 min

  • Platelet inhibition

    inhibition of platelet aggregation

    120 min

  • Platelet inhibition

    inhibition of platelet aggregation

    189 min

  • Platelet inhibition

    inhibition of platelet aggregation

    240 min

  • Platelet Inhibition

    inhibition of platelet aggregation

    360 min

  • Platelet Inhibition

    inhibition of platelet aggregation

    24 hours

Study Arms (5)

Part 1 Cohort 1

EXPERIMENTAL

Cohort 1: 0.05 mg/kg RUC-4/placebo 7 subjects will be enrolled: 6 subjects will receive a single subcutaneous dose of RUC-4 and 1 subject will receive matched placebo.

Drug: RUC-4 Compound

Part 1 Cohort 2

EXPERIMENTAL

Cohort 2: 0.075 mg/kg RUC-4/placebo 7 subjects will be enrolled: 6 subjects will receive a single subcutaneous dose of RUC-4 and 1 subject will receive matched placebo.

Drug: RUC-4 Compound

Part 2 Cohort 1

EXPERIMENTAL

Cohort 1: initial dose to be selected by the Safety Review Committee (SRC) after completion of Part 1 (the same initial dose used in Part 1 or one of the previously studied higher doses that is lower than the overall RUC-4 BED) 7 subjects will be enrolled: 6 subjects will receive a single subcutaneous dose of RUC-4 and 1 subject will receive matched placebo.

Drug: RUC-4 Compound

Part 2 Cohorts 2-3

EXPERIMENTAL

7 subjects (6 receiving RUC-4, 1 receiving placebo) will be enrolled in each dose cohort, with a safety evaluation performed after 2 subjects in a dose cohort receive RUC 4 and at the completion of dosing for all subjects in the dose cohort. Dose escalation to be determined by the SRC charter and will continue until identification of the overall RUC-4 BED or MTD

Drug: RUC-4 Compound

Part 2 Dose Expansion Cohort 1

EXPERIMENTAL

14 subjects will receive a selected dose of RUC-4 based on SRC review of dose escalation data. In the expansion cohort, 7 subjects weighing 55 to 65 kg and 7 subjects weighing 100 to 120 kg will be enrolled; 12 subjects will receive a single subcutaneous dose of RUC-4 and 2 will receive matched placebo

Drug: RUC-4 Compound

Interventions

RUC-4 CompoundDRUG

single subcutaneous administration of RUC-4

Also known as: Placebo
Part 1 Cohort 1Part 1 Cohort 2Part 2 Cohort 1Part 2 Cohorts 2-3Part 2 Dose Expansion Cohort 1

Eligibility Criteria

Age18 Years - 75 Years
Sexall(Gender-based eligibility)
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • weight between 55-120 kg, inclusive, and BMI between 18-38 kg/m2
  • females must be non-pregnant, non-lactating, and of non-childbearing potential.
  • good general health as determined by no acute illness and no clinically significant abnormal findings on medical history, clinical laboratory test results, vital signs, or physical examination
  • platelet count of 150,000/uL to 400,000/uL and mean platelet volume (MPV) within the normal range
  • Subjects with stable CAD, defined as history of documented myocardial infarction (MI) or angina, or evidence of CAD derived from cardiac stress test, or imaging (calcium score \[greater than 100 or abnormal for age\], angiography, computerized tomography, or magnetic resonance image); absence of angina, or presence of angina with no change in frequency, duration, precipitating causes or ease of relief for at least 60 days, and no ECG or biomarker evidence of myocardial damage in past 60 days
  • blood pressure control achieved with 4 or fewer anti-hypertensive medications
  • on a stable regimen of aspirin at a dose of 81 to 325 mg/day

You may not qualify if:

  • history of prior stroke or clinically significant cardiovascular (e.g., unstable angina, New York Heart Association \[NYHA\] class II, II or IV heart failure), dermatologic, endocrine, gastrointestinal (GI), hematologic, infectious, metabolic, neurologic, psychologic, or pulmonary disorder or any other condition, including active cancer that in the opinion of the PI would jeopardize the safety of the subject or impact the validity of the study results
  • history of upper or lower GI bleeding requiring intervention or treatment within 12 months of Screening or endoscopic evidence of active peptic ulcer disease within 6 months of Screening
  • bleeding score \> 3 on the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool
  • coagulation abnormality, bleeding disorder, or history of documented prior hemorrhagic or thrombotic stroke
  • whole blood donation and/or diagnostic blood evaluation exceeding 500 mL within 8 weeks of Screening
  • surgical procedure, major injury, or dental procedure with high risk of bleeding within 30 days of Screening
  • alcohol consumption of \>210 mL of alcohol per week within 6 months of Screening, or alcohol detected in urine at Screening
  • marijuana use within the past 3 months, or history/presence of substance abuse
  • febrile illness within 14 days of Screening
  • use of metformin within 7 days of Screening
  • use of herbal or nutritional supplements/medicines within 7 days of Screening
  • participation in another investigational product or device study within 30 days of Screening or during the study
  • Presence of HIV antibody, HCV antibody, or HbsAg in serum at Screening
  • employee of the Sponsor or The Lindner Center staff member directly affiliated with the study, or their immediate family member defined as spouse, parent, child, or sibling
  • abnormal platelet aggregation or in vitro inhibition of platelet aggregation pattern by RUC-4
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Lindner Research Center

Cincinnati, Ohio, 45219, United States

Location

Related Publications (1)

  • Kereiakes DJ, Henry TD, DeMaria AN, Bentur O, Carlson M, Seng Yue C, Martin LH, Midkiff J, Mueller M, Meek T, Garza D, Gibson CM, Coller BS. First Human Use of RUC-4: A Nonactivating Second-Generation Small-Molecule Platelet Glycoprotein IIb/IIIa (Integrin alphaIIbbeta3) Inhibitor Designed for Subcutaneous Point-of-Care Treatment of ST-Segment-Elevation Myocardial Infarction. J Am Heart Assoc. 2020 Sep;9(17):e016552. doi: 10.1161/JAHA.120.016552. Epub 2020 Aug 26.

    PMID: 32844723DERIVED

MeSH Terms

Conditions

Coronary Disease

Interventions

RUC-4 compound

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
The first 2 subjects in each dose cohort receive RUC-4 in a single- blind manner (only the subjects will blinded to treatment assignment), prior to randomizing the remaining 5 subjects to either RUC 4 (n = 4) or placebo (n = 1) in a double-blind manner.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 13, 2019

First Posted

February 18, 2019

Study Start

February 18, 2019

Primary Completion

November 1, 2019

Study Completion

December 1, 2019

Last Updated

August 27, 2024

Record last verified: 2024-08

Data Sharing

IPD Sharing
Will not share

Locations

US(1)