First-in-Human and Proof-of-Mechanism Study of ARC19499 Administered to Hemophilia Patients

The purpose of this study is to examine the safety, tolerability and the way the body handles various single and multiple doses of ARC19499 in patients with hemophilia.

Study Overview

• Status: Terminated
• Conditions: Hemophilia
• Intervention / Treatment: Drug: placebo control; Drug: ARC19499

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Adult male patients ≥18 to ≤75 years of age.

• Hemophilia of any type or severity.
• Patients who are negative for hepatitis B surface antigen (HBsAg), and human immunodeficiency virus (HIV) I and II antibody tests at screening.
• Male patients who, with their partners, are willing to use 2 effective, methods of contraception (i.e., for both self and partner) throughout the study and for at least 3 months after discontinuation of study drug treatment.
• All patients must be capable of understanding and complying with the protocol and must have signed the informed consent document.

Exclusion Criteria:

• Female patients;
• If on a prophylactic coagulation factor concentrate regimen, inability or unwillingness to discontinue prophylaxis during participation in this study.
• Existence of other co-existing bleeding disorder (e.g., von Willebrand Disease).
• Medical history of venous or arterial thromboembolism.
• Scheduled for elective surgical procedure during the conduct of this study.
• Use of an investigational drug within 30 days of study entry.
• Transaminase values > 3 x upper limit of normal (ULN) at time of screening.
• Haemoglobin <12.0 g/dL.
• Participants who, in the opinion of the Investigator, have a significant infection or known inflammatory process on screening.
• Participants who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders.
• Any medical condition the investigator believes would place the patient at increased risk as a result of participation in the study e.g. history of thromboembolic disease or stroke.
• Any medication the investigator considers may increase the risk of adverse effects during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: saline for injection	Drug: placebo control; sterile saline for injection
EXPERIMENTAL: ARC19499 Low Dose	Drug: ARC19499; Anti-tissue factor pathway inhibitor (TFPI) aptamer
EXPERIMENTAL: ARC19499 Mid Dose	Drug: ARC19499; Anti-tissue factor pathway inhibitor (TFPI) aptamer
EXPERIMENTAL: ARC19499 High Dose	Drug: ARC19499; Anti-tissue factor pathway inhibitor (TFPI) aptamer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of ARC19499	The PK profile of ARC19499 administered by single and multiple subcutaneous injections will be characterized. The bioavailability of subcutaneously injected ARC19499 relative to that of intravenously infused ARC19499 will be determined.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coagulation system pharmacodynamic (PD) effects of ARC19499.	The PD profile of ARC19499 with respect to the kinetics of thrombin generation and clot formation will be characterized.	2 weeks

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 15, 2010
• Primary Completion (ACTUAL): December 28, 2011
• Study Completion (ACTUAL): December 28, 2011

Study Registration Dates

• First Submitted: August 26, 2010
• First Submitted That Met QC Criteria: August 27, 2010
• First Posted (ESTIMATE): August 30, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 5, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hemophilia B; pharmacokinetics; pharmacodynamics; Hemophilia A; Tissue Factor Pathway Inhibitor
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: ARC19499-001; 2010-020373-17 (EUDRACT_NUMBER); 271101 (OTHER: Baxter Healthcare Corporation)