Safety, Pharmacokinetics and Efficacy of an AT-III Concentrate.

Condition(s) targeted: Antithrombin III Deficiency

Intervention: Plasma-derived AT-III concentrate (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Grifols Biologicals Inc.

Official(s) and/or principal investigator(s):
Paul J Pinciaro, PhD, Study Director, Affiliation: Grifols Biologicals Inc.

Overall contact:
Paul J Pinciaro, PhD, Phone: 410-814-7617, Email: paul.pinciaro@grifols.com

To assess the safety, pharmacokinetics and efficacy of a plasma-derived AT-III concentrate in the treatment of subjects with congenital AT-III deficiency.

Official title: A Phase II/III Pivotal Trial Evaluating the Safety, Pharmacokinetic Properties and Efficacy of a Plasma-Derived Anti-thrombin III Concentrate With Administration in Surgery, Pregnancy and Thromboembolic or Thrombotic Events.

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome:

The primary objectives of this clinical study are to:

Assess the pharmacokinetic (PK) profile of AT-III in congenital AT-III deficient patients

To measure the in vivo recovery and half-life of AT-III.

To assess the clinical safety and tolerability of AT-III-DAF/DI.

Secondary outcome: To assess clinical efficacy by preventing thromboembolic or thrombotic events (prophylaxis) in individuals with congenital AT-III deficiency who are undergoing surgical procedures or who are pregnant and undergoing parturition.

Detailed description: This study will be a prospective, unblinded, non-randomized, open-label, multi-center Phase II/III study with 2 segments, i. e. a PK evaluation (Segment I), and an assessment of prophylaxis in surgical interventions and pregnancy/delivery, (Segment II). During the PK segment, the subjects would remain on their current anticoagulation therapy except for subjects on heparin therapy where a wash-out period of at least 5 half lives would be required. In total, 15 subjects with congenital ATIII Deficiency will be enrolled for the PK assessment (Segment I).

For Segment II, fifteen episodes will be treated. Recruitment of individual subjects with high risk for venous thrombosis for Segment II of this study is necessary because of the rarity of Antithrombin deficiency in the population.

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Congenital ATIII deficiency documented by determination of plasma levels of ATIII off

all therapies. Specifically, the baseline levels of ATIII activity should be equal to or less than 60%.

- Age > 12 years with a body weight of no less than 30 kg.

- Have not participated in another investigational study for at least 30 days For

Segment II, enrollment requires a pregnancy/delivery or a surgical procedure (it should be a major surgery although data from a minor surgery will also be collected).

- Documented personal history of major thromboembolic or thrombotic event.

- Male or female

- HIV, HBV, HCV, HAV and PARVO B19 status known prior to entry.

- The subject is willing to comply with all aspects of the protocol, including blood

sampling, for the duration of the study.

- The subject has signed an informed consent form (if at least 18 years old), or the

subject's parent or legal guardian has signed the informed consent form. Subjects below the age of 18 years will also be asked to sign an assent form. All consent and assent forms must be approved in advance by the Institutional Review Board of the investigator's institution.

- Patients with heparin-associated thrombocytopenia who require anticoagulation with

non-heparin containing drugs will be eligible if they can be safely transitioned during the washout period for the Segment I PK study.

- If pregnant, a woman must be Parvo B19 IgG antibody positive.

Exclusion Criteria:

- Acquired deficiency of ATIII

- Receiving concomitant treatment for thrombophilic disorders other than ATIII

deficiency

- Inability or unwillingness to comply with the protocol requirements

- History of anaphylactic reaction(s) to blood or blood components

- Allergies to excipients.

- Liver function tests >/= 2. 5 X ULN

- Serum creatinine >1. 2 X ULN

- Urine >/= 2+ protein with urine dipstick test.

- The subject is known to have abused alcohol or illicit drugs within the past 12

months.

- The subject is unlikely to adhere to the protocol requirements of the study or is

likely to be uncooperative or unable to provide a storage serum sample at the screening visit.

- Patients on heparin-treatment who, for clinical reasons, cannot safely be

discontinued from heparin therapy during the PK segment.

Paul J Pinciaro, PhD, Phone: 410-814-7617, Email: paul.pinciaro@grifols.com

New York Presbyterian Hospital-Weill Cornell, New York, New York 10021, United States; Not yet recruiting
Dan Matulich, Email: dam2027@med.cornell.edu

University of Texas Health Science Center, Houston, Texas 77030-4009, United States; Recruiting
Kathryn L. Moynihan, Phone: 713-500-8376, Email: kathryn.l.moynihan@uth.tmc.edu
Madeline Cantini, Phone: 713-500-8377, Email: madeline.cantini@uth.tmc.edu

University of Virginia Health System, Charlottesville, Virginia 22908-1370, United States; Recruiting
Winsor D. Simmons, RN, Phone: 434-243-0315, Email: wds5j@virginia.edu

Starting date: January 2006
Last updated: August 30, 2012