Prospective Studies on the Impact of Generic Immunosuppressants on Acute Rejection and Long Term Graft survivals (U01)

Post Date

April 18th 2014

Application Due Date

June 21st 2014

Funding Opportunity Number

RFA-FD-14-020

CFDA Number(s)

93.103

Funding Instrument Type(s)

Cooperative Agreement

Funding Activity Categories

Health
Science and Technology and other Research and Development

Number of Awards

1

Eligibility Categories

State Governments
County Governments
City or Township Governments
Special District Governments
Independent School Districts
Public and State Controlled Institutions of Higher Education
Federally Recognized Native American Tribal Governments
Public Housing Authorities or Indian Housing Authorities
Non-Federally Recognized Native American Tribal Organizations
Non-Profits With 501 (c) (3) Status With The IRS (Except Higher Education Institutions)
Non-Profits Without 501 (c) (3) Status With The IRS (Except Higher Education Institutions)
Private Institutions of Higher Education
For-Profit Organizations (Except Small Businesses)
Small Businesses
Other

Foreign Recipients

Funding

• Estimated Total Funding:

  $4000000

• Award Range:

  $750000 - $1000000

Grant Description

Background: Survival after solid organ transplantation has increased substantially due in part to the broad clinical use of immunosuppressants. Immunosuppressive regimens typically include a combination of a calcineurin inhibitor (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate mofetil, mycophenolate sodium, or azathioprine), and corticosteroids. Proliferation signal inhibitors, e.g., sirolimus, may also be used either in combination with a calcineurin inhibitor or antiproliferative agent, or as a replacement for one. Availability of generic versions for these immunosuppressants allows for reduced drug costs that translate to increased drug access and significant cost savings for both insurers and patients. Maintenance of the immunosuppressive balance is critical for allograft patency, minimization of adverse effects, and ultimately long-term survival of solid organ transplant recipients. The question whether the brand to generic switch or switch among multiple generic products may introduce clinically relevant changes in drug exposure and thus affect clinical safety and efficacy remains debated in transplant community. To address transplant communityуs concern, FDA funded research studies to compare the pharmacokinetics (PK) of approved generic tacrolimus capsules to Prograf (brand product) in stable liver and kidney adult transplant patients with moderate and high immunological risk. However, the impact of introduction of generic immunosuppressants on long term graft survival was never systematically evaluated in well controlled clinical studies. These clinical outcome studies are critically needed to confirm the therapeutic equivalence of generic immunosuppressants with the brand product, thereby increasing transplant community confidence on the use of generic immunosuppressants. Objectives: The objective of this study is to conduct prospective clinical studies to investigate the impact of generic immunosuppressants on short term acute rejection and long term patient graft survival. The outcome of this study will help respond to public concerns regarding the interchangeability of generic immunosuppressants and improve review practices of generic immunosuppressants if necessary. The results obtained from this study can be compared to those of retrospective analysis, providing comprehensive perspectives and better research options regarding generic immunosuppressant interchangeability. Detailed Descriptions: The model drugs to be studied can include cyclosporine, tacrolimus, mycophenolate mofetil, mycophenolate sodium, and sirolumus. The project may include the following: 1. Conduct prospective, open-label, randomized, multicenter, parallel, 3-year (or longer) observational study in kidney, heart, liver transplant recipients using any model drug or drug combination listed above. 2. Assess the safety and efficacy profiles in patients taking brand immunosuppresants only, generic immunosuppressants only, or both brand and generic immunosuppressants. Further subgroup analysis in children, adults, and African Americans is recommended. Patient and graft survival, severity of biopsy-proven acute rejection and other efficacy points will be monitored. Methods such as properly scheduled visits at the transplantation centre, phone monitoring, and patients self-monitoring should be employed. Safety can be assessed based on treatment-emergent adverse events, the results of routine clinical laboratory tests, and vital sign measurements at time intervals relevant for particular transplantation type and type of medicinal product under evaluation. 3. Evaluate patient adherence to the immunosuppressive regimen, as well as the frequency and extent of dosage adjustment 4. If therapeutic drug monitoring is routinely used, drug concentration data should be collected and evaluated.

Contact Information

• Agency

  Department of Health and Human Services

• Office:

  Food and Drug Administration

• Agency Contact:

  Gladys Melendez-Bohler
  Grants Management Officer/Specialist
  Phone 240-402-7565

• Agency Mailing Address:

  FDA Office

• Agency Email Address:

  gladys.bohler@fda.hhs.gov

• More Information:

  Copy of published RFA