Evaluation of Clot Stability Induced by Solulin: Evaluation of New Solulin Mutants Lacking Protein C Activation Capacity

NCT02911233 | Completed

• 1 other identifier: 13-136
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Hemophilia A is a rare X chromosome-linked recessive bleeding disorder that concerns one individual in 5000. In its severe form, hemophilia A is a life-threatening, crippling hemorrhagic disease. The treatment of bleeding episodes in hemophilia A patients involves the administration of exogenous human FVIII to restore normal hemostasis. The main complication of the substitutive treatment of hemophilia A is the development, in 15 to 30% of the cases, of anti-FVIII antibodies (FVIII inhibitors) that neutralize the pro-coagulant activity of therapeutically administered FVIII. In 2003, the average annual cost of care for a patient with hemophilia A was evaluated to be equal to 63,000 euros (2), which, in France (6000 patients), represents an annual budget of 378 million euros. In order to reduce the cost of treatment and to bypass this complication, different therapeutic strategies (new products or adjunctive therapeutic options) have been explored, including platelet infusion, tranexamic acid, amino caproic acid, molecules that block tissue factor pathway inhibitor, combination of phospholipid -Factor Xa- Factor XIII and antibodies directed to the Tissue Factor Inhibitor Pathway (TFPI). Recently, Soluble thrombomodulin (Solulin) have been developed. This molecule may be used to partially correct the premature lysis defect in Factor VIII deficient plasma through an activated TAFI - dependent mechanism. With a long half-life (15- to 30-hour) and effective dose range estimated to range from the sub-nanomolar to approximately 40nM, Solulin could potentially be administered on a weekly basis and provide the basis for a factor-sparing regime that would cut costs and make therapy more widely available. However, before proceeding to advanced trials, safety concerns stemming from the anticoagulant properties of Solulin must be addressed. The development of Solulin mutants lacking protein C activation capacity would make this concern redundant. At the same time, such mutant molecules are likely to possess an effective dose range. Our project is to compare the behavior of recombinant Solulin and mutants of Solulin lacking protein C activation capacity with respect to their ability to stabilize fibrin clots in whole blood of humans with different coagulation factor deficiencies (hemophilia A, hemophilia B and rare blood coagulation deficiencies (factor X, VII, V).

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (2)

• Evaluation of blood clot firmness in ROTEM experiments using mutant Solulin

  2 hours

• Evaluation of fibrinolysis in ROTEM experiments using mutant Solulin

  2 hours

Interventions

Thromboelastograpgy BIOLOGICAL

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

\- Patients with congenital blood disorder hemophilia A and B

You may qualify if:

• Patients with congenital blood disorder (hemophilia A and B),
• Inform consent

You may not qualify if:

• Patients with acquired blood disorder.
• Allo-immunisation against blood coagulation factor concentrates (FVIII inhibitor)

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

University Hospital

Caen, Calvados, 14000, France

Location

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 22, 2016
• Study Start: March 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: September 22, 2016

Record last verified: 2016-09

Locations

FR (1)