Hemophilia Inhibitor Previously Untreated Patient Study

NCT01652027 | Completed DMC

• 1 other identifier: HSC-MS-11-0202
• Study Type: observational
• Target: 25
• Locations: 5 countries
• Sites: 17

Brief Summary

Hemophilia A is a congenital bleeding disorder caused by deficiency of factor VIII (FVIII) and is treated by replacement therapy with FVIII concentrate. Approximately 30% of people with severe hemophilia A develop neutralizing antibodies, called FVIII inhibitors, which interfere with the function of FVIII concentrates. The reason that some, but not all, people with severe hemophilia A develop inhibitors is incompletely understood. Understanding individual and environmental risk factors is important to be able to prevent and possibly treat inhibitors. This study will look at individual and treatment characteristics in babies with severe hemophilia A who have not yet received treatment with FVIII (called Previously Untreated Patients, or PUPS). Subjects in the study will be asked to provide diaries of treatments, medications, and illnesses. Treatment will be directed by the subjects' physician, but all subjects will receive Advate, a third-generation recombinant FVIII product. Subjects will have blood drawn for laboratory tests, which include studies of the immune system and genetic studies of the FVIII mutation, before and 7-9 days after the first treatment with FVIII, and 5 days (+/-2 days) after the 5th, 10th, 20th, 30th, 40th, and 50th days of treatment with FVIII (exposure days). The duration of the study will be first 50 treatments or 3 years, whichever comes first.

Conditions

Hemophilia A

Keywords

FVIII inhibitors

Outcome Measures

Primary Outcomes (1)

• Total number of FOXP3-positive T regulatory cells in the circulation

  FoxP3(a protein involved in immune system responses)-positive T regulatory cells in the circulation will be compared before and after exposure to FVIII.

  50 exposure days to FVIII or 3 years, whichever comes first

Secondary Outcomes (1)

• FVIII-specific T-cells

  50 exposure days to FVIII or 3 years, whichever comes first

Study Arms (1)

Previously Untreated Patients with Hemophilia A

Drug: FVIII concentrate

Interventions

FVIII concentrate DRUG

usual treatment as directed by treating physician

Previously Untreated Patients with Hemophilia A

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with severe hemophilia A who have not previously been treated with Factor VIII concentrates.

You may qualify if:

• Severe hemophilia A with FVIII activity \< 1% normal
• Weight \> 3.5 kg at the time of baseline study evaluation
• Informed consent, approved by appropriate Institutional Review Board/Independent Ethics Committee, has been administered, signed, and dated

You may not qualify if:

• Prior exposure to clotting factor concentrates or blood products
• Other chronic disease
• Currently participating in another investigational drug study.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• Rho, Inc.: collaborator
• Baxter Healthcare Corporation: collaborator

Study Sites (17)

Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Cornell University

New York, New York, 10065, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

University of Oregon

Portland, Oregon, United States

Location

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, 15213, United States

Location

North Texas Comprehensive Hemophilia Center

Dallas, Texas, 75235, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center-Houston

Houston, Texas, 77030, United States

Location

Intermountain Hemophilia and Thrombosis Center

Salt Lake City, Utah, 84108, United States

Location

Medical University of Vienna

Vienna, A-1090, Austria

Location

Angelo Bianchi Bonomi Hemophilia & Thrombosis Center

Milan, 20122, Italy

Location

Emma Children's Hospital AMC

Amsterdam, 1105, Netherlands

Location

Malmo Centre for Thrombosis and Haemostasis

Malmo, Se-205 02, Sweden

Location

Related Publications (2)

• Paul H, Berg V, Gangadharan B, Bowen J, LeBeau P, Blatny J, Male C, Radulescu VC, Diaz R, Mancuso ME, Brown DL, Reipert BM. Prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures during FVIII inhibitor eradication. Blood Adv. 2023 May 9;7(9):1831-1848. doi: 10.1182/bloodadvances.2022007267.

  PMID: 36074992 DERIVED

• Reipert BM, Gangadharan B, Hofbauer CJ, Berg V, Schweiger H, Bowen J, Blatny J, Fijnvandraat K, Mullins ES, Klintman J, Male C, McGuinn C, Meeks SL, Radulescu VC, Ragni MV, Recht M, Shapiro AD, Staber JM, Yaish HM, Santagostino E, Brown DL. The prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures prior to FVIII inhibitor development. Blood Adv. 2020 Nov 24;4(22):5785-5796. doi: 10.1182/bloodadvances.2020002731.

  PMID: 33232473 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Plasma samples, lymphocyte cell lines, Genomic DNA, RNA

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 Officials

• Elena Santagostino, M.D.

  Maggiore Hospital and University of Milan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 3, 2011
• First Posted: July 27, 2012
• Study Start: July 1, 2011
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2020
• Last Updated: November 10, 2020

Record last verified: 2020-11

Locations

SE (1); AU (1); US (13); IT (1); NL (1)