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A Randomized Phase 1 Dose-Escalation Study of Subcutaneously(SC) Administered RUC-4

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ClinicalTrials.gov Identifier: NCT03844191
Recruitment Status : Recruiting
First Posted : February 18, 2019
Last Update Posted : March 5, 2019
Sponsor:
Collaborators:
Precision For Medicine
CirQuest Labs
CRL
Information provided by (Responsible Party):
CeleCor Therapeutics

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 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).

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.


Condition or disease Intervention/treatment Phase
Coronary Disease Drug: RUC-4 Compound Phase 1

Detailed Description:

Part 1 Dose Escalation:

Drug: RUC-4 0.05 mg/kg (Cohort 1) Drug: RUC-4 0.1 mg/kg (Cohort 2) Drug: RUC-4 0.3 mg/kg (Cohort 3) Drug: RUC-4 (Cohorts 4-7 doses to be defined) Drug: Placebo (Cohorts 1-7)

Part 2 Dose Escalation Drug: RUC-4 (Cohort 1-7 doses to be defined) Placebo (Cohorts 1-7)

Part 2 Dose Expansion Drug: RUC-4 (dose to be defined, up to 2 Cohorts) Drug: Placebo (up to 2 Cohorts)


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: A Randomized Phase 1 Dose-Escalation Study in Healthy Volunteers and Subjects on Aspirin With Stable Coronary Artery Disease to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous RUC-4
Actual Study Start Date : February 18, 2019
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 Cohort 1
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
single subcutaneous administration of RUC-4

Experimental: Part 1 Cohort 2
Cohort 2: 0.1 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
single subcutaneous administration of RUC-4

Experimental: Part 1 Cohort 3
Cohort 3: 0.3 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
single subcutaneous administration of RUC-4

Experimental: Part 1 Cohort 4-7
Dose to be determined. 7 subjects will be enrolled per Cohort: 6 subjects will receive a single subcutaneous dose of RUC-4 and 1 subject will receive matched placebo.
Drug: RUC-4 Compound
single subcutaneous administration of RUC-4

Experimental: Part 2 Cohort 1
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
single subcutaneous administration of RUC-4

Experimental: Part 2 Cohorts 2-7
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
single subcutaneous administration of RUC-4

Experimental: Part 2 Dose Expansion Cohort 1

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
single subcutaneous administration of RUC-4

Experimental: Part 2 Dose Expansion Cohort 2

14 subjects will receive a different selected dose of RUC-4 based on SRC review of Cohort 1 dose expansion 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
single subcutaneous administration of RUC-4




Primary Outcome Measures :
  1. Platelet Inhibition [ Time Frame: 5 minutes ]
    inhibition of platelet aggregation

  2. Platelet inhibition [ Time Frame: 15 min ]
    inhibition of platelet aggregation

  3. Platelet inhibition [ Time Frame: 30 min ]
    inhibition of platelet aggregation

  4. Platelet inhibition [ Time Frame: 60 min ]
    inhibition of platelet aggregation

  5. Platelet inhibition [ Time Frame: 90 min ]
    inhibition of platelet aggregation

  6. Platelet inhibition [ Time Frame: 120 min ]
    inhibition of platelet aggregation

  7. Platelet inhibition [ Time Frame: 189 min ]
    inhibition of platelet aggregation

  8. Platelet inhibition [ Time Frame: 240 min ]
    inhibition of platelet aggregation

  9. Platelet Inhibition [ Time Frame: 360 min ]
    inhibition of platelet aggregation

  10. Platelet Inhibition [ Time Frame: 24 hours ]
    inhibition of platelet aggregation



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

Main Inclusion Criteria (all subjects)

  • 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 200,000/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

Main exclusion criteria (all subjects):

  • 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
  • receiving or have received in the past 30 days an anticoagulant or fibrinolytic agent
  • a cardiac pacemaker
  • history of allergy to any of the ingredients in the RUC-4 or placebo formulation

Healthy Subjects only:

  • medication known to have an impact on platelet function within 30 days of Screening.
  • abnormally low response to arachidonic acid-induced platelet aggregation
  • screening ECG abnormality that is interpreted by the PI to be clinically significant

Stable CAD subjects only:

  • medication known to have an impact on platelet function, with the exception of aspirin, within 30 days of Screening.

    ->4 anti-hypertensive medications required to achieve blood pressure control

  • incomplete inhibition of arachidonic acid-induced platelet aggregation
  • acute changes on ECG

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03844191


Contacts
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Contact: Robert S Hillman, PhD 8587779750 rhillman@celecor.com

Locations
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United States, Ohio
The Lindner Research Center Recruiting
Cincinnati, Ohio, United States, 45219
Principal Investigator: Dean Kereiakes, MD         
Sponsors and Collaborators
CeleCor Therapeutics
Precision For Medicine
CirQuest Labs
CRL

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Responsible Party: CeleCor Therapeutics
ClinicalTrials.gov Identifier: NCT03844191     History of Changes
Other Study ID Numbers: CEL-01
First Posted: February 18, 2019    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases