Immune-based therapies: A review of clinical endpoints used in trials of selected immunologic agents,by the Forum for Collaborative HIV Research

Abstract

While the use of highly active antiretroviral therapy (HAART) has lowered the level of virus in the bloodstream, immune reconstitution may offer additional benefits in maintaining viral suppression and enhancing immune function. New approaches in immune-based therapy (IBT) must be designed to capture endpoints that will allow approval of these agents by regulatory agencies.The challenge is to identify, develop, and validate biomarkers that can serve as endpoints in evaluating the efficacy of immunologic agents in HIV disease.

On December 7-8, 2000, the Forum for Collaborative HIV Research sponsored a workshop, “Immune-Based Therapies and HIV Disease.” Some of the questions discussed at that meeting included: ? What are the appropriate indices to measure immune competence?

? What are the appropriate research designs and endpoints for trials evaluating IBTs?

? What can we learn from the research on IBTs in diseases other than HIV?

? What are the requirements of regulatory agencies for the approval of IBTs?

This report, prepared as background information for participants attending the December workshop, addresses issues related to these discussion questions. The report provides a review of study designs and endpoints used in clinical trials of selected immunologic agents. Eight ofthese agents have been approved by the U.S. Food and Drug Administration (FDA) for use in disease conditions other than HIV and five agents are under study for use in HIV-infected individuals but are not FDA-approved for use in HIV disease.

This report was written by Karen Eddleman, who has derstanding of the medical management of HIV disease and develops recommendations to fill those gaps. The Forum is a public/private partnership, which receives financial support from its governmental and industry members and with in-kind support from its membership within the academic research, patient care, and advocacy communities. For more information about the Forum or to download this report or prior ones, visit the Website at www.hivforum.org. Reprinted with permission from Forum for Collaborative HIV Research (www.hivforum.org).done a remarkable job in identifying and reviewing many difficult references and producing a very reader-friendly report. Alan Landay has provided valuable input andassistance in the creation of this report. Houtan Movafagh provided much needed assistance in finding and copying the many references for this report.

June Bray, PhD – Deputy Director