Cangrelor Neonatal PK/PD and Safety Study

A Prospective, Open-Label, Single-Arm, Multi-Center Study To Assess The Pharmacokinetics/Pharmacodynamics (PK/PD) And Safety Of Different Cangrelor Doses In Neonatal Subjects At Risk Of Thrombosis

The purpose of this study is to assess the PK/PD and safety profile of cangrelor in neonatal participants at risk of thrombosis.

Study Overview

• Status: Completed
• Conditions: Partial Obstruction of Systemic to Pulmonary Artery Shunt; Complete Obstruction of Systemic to Pulmonary Artery Shunt
• Intervention / Treatment: Drug: Cangrelor

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Males and females with congenital heart disease, and ranging in age from birth through 28 days of life
2. Postoperative neonatal cardiac participants with placement of systemic-to-pulmonary artery palliative shunts, right ventricle to pulmonary artery palliative shunts, or ductus arteriosus stents who are at risk of thrombotic events after repair for structural congenital heart disease.
3. Written informed consent from a parent/legal guardian
4. Life expectancy of at least 15 days at study entry

Participants will be excluded from the study if any of the following exclusion criteria apply:

1. History of intracerebral bleed (confirmed by a ultrasound (US) of the head prior to surgery), or cerebral arteriovenous malformation, or any prior bleed with neurological deficit
2. Gastrointestinal or urinary bleeding
3. Cerebrovascular accident or any cerebrovascular accident with a residual neurological deficit
4. Known congenital or acquired bleeding or clotting disorder
5. Weight less than 2.5 kilograms (kg)
6. Adjusted gestational age less than 37 weeks
7. Platelet count less than 100,000 cells/microliter (µL)
8. Chest and/or mediastinal tube blood output of greater than 3 milliliters (mL)/kg/hour (hr) at the time of cangrelor administration
9. Participants with evidence of severe hepatic or renal failure [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than three times normal for age or total bilirubin greater than 20 milligrams (mg)/deciliter (dL); creatinine greater than 2 times the normal upper limit]
10. Known allergy to cangrelor or known sensitivity to any component of cangrelor
11. Any condition that in the investigator's opinion would constitute a contraindication to participation in the study or cause inability to comply with the study requirements
12. Participation in another investigational therapeutic drug or investigational therapeutic device trial within 30 days of starting study
13. Participants who have been receiving warfarin (Coumadin®) therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cangrelor; Cangrelor in up to four (4) dose cohorts consisting of a minimum of five participants in each cohort. One cohort of five participants will be enrolled at a time. Cohort 1 subjects will receive Cangrelor at 0.5 mcg/kg/min. Cohort 2 subjects will receive Cangrelor at 0.25 mcg/kg/min. Subsequent cohort dosing decisions are made at the completion of enrollment in each cohort.	Drug: Cangrelor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total plasma concentrations of cangrelor and its primary metabolite, AR C69712, during administration and after cessation of the infusion in neonates	During study drug infusion through 8 hours post infusion
Proportion of participants in each cohort who achieve ≥90% inhibition of final platelet aggregation as measured by light transmittance aggregometry (LTA) using 20 micromolar (µM) adenosine diphosphate (ADP) in platelet rich plasma	During study drug infusion through 1 hour post infusion
Individual recovery of platelet function in neonates after cessation of the infusion	Up to 1 hour post infusion
Assessment of the safety of cangrelor in neonatal participants by evaluating adverse events (AEs) and serious adverse events (SAEs)	from start of cangrelor infusion through 48 hours post cangrelor infusion

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.

Publications and helpful links

General Publications

• Vargas D, Zhou H, Yu X, Diamond S, Yeh J, Allada V, Krishnamurthy G, Price M, Allen B, Alexander J, Schmidhofer J, Kreutzer J, Vincent J, Morell V, Bacha E, Diacovo T. Cangrelor PK/PD analysis in post-operative neonatal cardiac patients at risk for thrombosis. J Thromb Haemost. 2021 Jan;19(1):202-211. doi: 10.1111/jth.15141. Epub 2020 Nov 29.

Helpful Links

• Study Record on EU Clinical Trials Register including results

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2017
• Primary Completion (Actual): August 31, 2019
• Study Completion (Actual): December 23, 2019

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: May 4, 2016
• First Posted (Estimate): May 6, 2016

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Cangrelor
• Other Study ID Numbers: MDCO-CAN-15-01; 2016-000134-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No