Clinical trial NCT03185897: Global Epidemiologic Study of Preexisting Immunity to AAV in Adults With Severe Hemophilia
Official title: A Global Epidemiologic Study to Determine the Prevalence of Neutralizing Antibodies and Related Adaptive Immune Responses to Adeno-Associated Virus (AAV) in Adults With Hemophilia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia A
Hemophilia B
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-06-14
Enrollment: 242
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hemophilia A and hemophilia B patients who receive treatment at Hemophilia Treatment Centers.

Brief summary: Assess the seroprevalence of neutralizing antibodies (NAb) to AAV in adults with severe hemophilia A (coagulation factor VIII \[FVIII\] \<1%) or moderately severe to severe hemophilia B (coagulation factor IX \[FIX\] ≤2%).


Eligibility criteria: Inclusion Criteria:

1. Participant is male between 18 and 75 years old at the time of screening.
2. Established severe hemophilia A (plasma Factor VIII (FVIII) activity \<1%) or B (plasma Factor IX (FIX) activity ≤2%).
3. Provision of signed informed consent form (ICF).
4. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

1. Bleeding disorder(s) other than hemophilia A or B.
2. Personal laboratory evidence of having developed inhibitors to FVIII or FIX protein at any time (≥0.6 Bethesda Units \[BU\] on any single test).
3. Currently receiving systemic immunosuppressive therapy, cytotoxic chemotherapy, immunoglobulin therapy, or monoclonal antibody therapy.
4. Received systemic antiviral and/or interferon therapy within 30 days of blood draw, with the exception of treatment for human immunodeficiency virus (HIV).
5. Currently receiving ribavirin and/or interferon based therapy for active hepatitis C virus (HCV).
6. Received immunoglobulin therapy or plasma infusion within 120 days of the blood draw.
7. Has a known immune deficiency other than HIV.
8. Has lymphocyte or plasma cell malignancies.
9. Participant is a family member or employee of the investigator.

Primary outcomes:
measure: Prevalence of neutralizing antibodies (NAb) - Baseline visit
timeFrame: Baseline visit
measure: Prevalence of neutralizing antibodies (NAb) - Year 1 Visit
timeFrame: Year 1 visit
measure: Prevalence of neutralizing antibodies (NAb) - Year 2 Visit
timeFrame: Year 2 visit
measure: Prevalence of neutralizing antibodies (NAb) - Year 3 Visit
timeFrame: Year 3 visit
Secondary outcomes:
measure: Prevalence of NAb to AAV including AAV2 and AAV8
timeFrame: Baseline visit, Year 1 visit, Year 2 visit, and Year 3 visit
measure: Prevalence of binding antibodies to AAV, including AAV8 and AAV2
timeFrame: Baseline visit, Year 1 visit, Year 2 visit, and Year 3 visit
measure: T-cell mediated immune response to AAV8
timeFrame: Baseline visit, Year 1 visit, Year 2 visit, and Year 3 visit
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Orthopaedic Hemophilia Treatment Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hemophilia & Thrombosis Center
state: Colorado
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Houston
country: United States
facility: Gulf States Hemophilia and Thrombophilia Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Vienna
country: Austria
facility: AKH - Medizinische Universität Wien
city: Brest Cedex
country: France
facility: Hôpital Morvan
city: Bron cedex
country: France
facility: Groupement Hospitalier Est- Hôpital Louis Pradel
city: Le Kremlin Bicêtre cedex
country: France
facility: Groupement Hospitalier Sud - Hôpital Bicêtre
city: Lille Cedex
country: France
facility: Hopital Jeanne de Flandre - CHU Lille
city: Marseille Cedex 05
country: France
facility: Hôpital de la Timone
city: Nantes Cedex 1
country: France
facility: CHU de Nantes Site Hotel Dieu
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet
city: Castelfranco Veneto
country: Italy
facility: Presidio Ospedaliero di Castelfranco Veneto
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Vicenza
country: Italy
facility: Ospedale San Bortolo di Vicenza
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: