Important note: Information in this article was accurate in 2006. The state of the art may have changed since the publication date.
Food and Drug Administration - February 10, 2006
Richard Klein, Kimberly Struble
As described in a November 21, 2005 list serve announcement, the purpose of this meeting will be to discuss issues regarding the development of CCR5 co-receptor antagonists for the treatment of HIV infection, specifically mechanisms for long-term follow-up of patients enrolled in CCR5 antagonist clinical trials, potential consequences of tropism changes, and characterization of resistance to these investigational agents.
Please consider contributing suggestions, your experiences and lessons learned from other long-term (>48 weeks) follow-up studies in HIV- infected subjects, as well as experiences from other therapeutic areas and innovative suggestions for collection of long-term safety data. This information will be used to formulate issues for presentation and discussion at the meeting.
To prepare for this meeting, we are requesting the following:
1. Detailed summaries regarding your experiences and lessons learned from long term follow-up studies (for the treatment of HIV infection or relevant experiences from other therapeutic areas) through the conduct of controlled clinical trials, open-label safety studies, observational cohorts or registries
2. Final or draft protocol(s) under consideration, or proposed outlines for long-term safety follow-up
3. Comments regarding any protocol design elements for long-term follow- up trials that were found unacceptable by the HIV community (patients and investigators) In addition, we are interested in suggestions for any related issues that you feel should be discussed at this meeting.
4. Comments on the topics and questions listed below
Your feedback on the following topics is requested:
A. Tropism and Safety Issues:
* Are there other potential adverse effects to the immune system that require additional monitoring? Please provide abstracts and/or publications (including unpublished data and/or manuscripts in press) you think are relevant to this topic.
B. Long-term Monitoring Plan - Currently the FDA is requesting five years of follow-up for patients who experience virologic failure in phase II and III CCR5 co-receptor antagonist studies. We recommend that sponsors evaluate patients two-three times a year for CD4+ cell counts, viral load, viral tropism, and occurrence of AIDS-defining illnesses and death.
* What are the feasibility concerns for the five-year follow-up commitment?
* What mechanisms can be used to ensure sufficient data collection and minimize lost-to-follow-up?
* Please provide suggestions on adequate control groups for comparative safety evaluation.
* Please provide proposals for data analyses for the long-term follow-up studies.
* Please provide additional alternative proposals for long-term monitoring, including other disease models.
* What type of studies can be designed to further establish the relationship between viral tropism and pathogenesis?
C. Resistance/Tropism Issues:
* Please comment on the amount and type of resistance/tropism information needed at the time of approval of new CCR5 antagonists.
D. Other:
* Please comment on the role of CCR5 antagonists in the antiretroviral armamentarium.
* Please comment on the potential role of tropism/resistance testing in clinical practice (e.g., routine, optional, none).
* Given the issues previously discussed are there any special/additional concerns for pediatric drug development?
During the meeting we intend to differentiate between information needed at the time of approval versus post-approval and between academic/investigator-initiated studies. Please keep this distinction in mind as you prepare your responses.
Please send your responses to blg@gwu.edu.
Register for the meeting here: http://www.hivforum.org/CCR5/signup_form.html
If you have any questions, please contact:
Rebecca Griesse -- blg@gwu.edu
Richard Klein, Office of Special Health Issues - Food and Drug Administration
Kimberly Struble, Division of Antiviral Drug Products - Food and Drug Administration
060210
FD060201
SOURCE: Food and Drug Administration (FDA).
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