CMV: Oral Ganciclovir Studies Open

Two clinical trials testing oral ganciclovir in people with CMV infection have recently opened at seven centers around the United States. The larger study is for people with newly diagnosed CMV retinitis. The second trial is designed to evaluate the effects of food on the absorption of oral ganciclovir. It will last eight days and is open to people with a past or present CMV infection (documented by a positive CMV culture or the presence of antibodies against CMV) without any evidence of CMV-related disease. Note that most people have been exposed to and infected with CMV at some time in their lives, but only some will develop symptoms related to that infection.

Background on CMV Treatments

Intravenous (IV) ganciclovir (also called DHPG, or Cytovene) is currently the only FDA-approved treatment for CMV retinitis, a sight-threatening infection of the eye. People who have been diagnosed with CMV retinitis are generally given ganciclovir twice a day for two to three weeks (induction phase) followed by daily infusions five to seven days a week for the rest of their lives (maintenance phase). If a person experiences a progression of their disease during the maintenance phase, they are generally re-induced with twice a day ganciclovir for another two to three weeks.

If the treatment fails to prevent progression of the retinitis after repeated inductions, or if the side effects of the ganciclovir are too serious to continue treatment, people may choose to try the experimental drug foscarnet. Although this compound is not yet FDA-approved, it is usually available to people in these situations through an expanded access program. Foscarnet is also an IV drug.

Several oral and other experimental anti-CMV drugs are currently in various stages of development. The oral compound which has been studied most is ganciclovir. In early studies it was found that the drug was not well absorbed; therefore, quantities much larger than the IV dosage must be taken to achieve concentrations high enough to be effective.

CMV Retinitis Study

The new study in people with CMV retinitis will compare oral and IV ganciclovir as maintenance treatment, after all participants have received a three week induction course with IV ganciclovir. This is an extremely important study because it will answer questions about the relative safety and efficacy of the oral and IV formulations. If the oral compound is found to be about as safe and effective as the IV drug, data from this study may lead to FDA licensing of oral ganciclovir.

To be eligible for this study, the CMV retinitis must have been diagnosed, and no anti-CMV drugs may have been used, within one month of enrollment. Participants cannot have persistent diarrhea or other gastrointestinal symptoms, because these are some of the potential side effects of oral ganciclovir. Participants must be at least 13 years old. Because this drug causes birth defects in animals, both males and females will be required to use birth control, and women will be required to have a negative pregnancy test.

Initiation or resumption of AZT will be allowed after the first five weeks of the study. ddI may be initiated or continued at any time during the study. ddC is not yet allowed, but an amendment may be written to include ddC and/or combination antiretroviral therapy at some point during the study as more data becomes available about the efficacy of these treatment approaches.

After the first three weeks of twice daily IV infusions of ganciclovir, participants will be randomized to receive either oral ganciclovir (two capsules six times a day while awake) or IV ganciclovir (once a day, seven days a week). Some patients treated outside of this study would only receive IV ganciclovir five days a week after the first two to three weeks, depending on blood counts and the preference of the patient and the physician. Randomization to the IV arm of this study may therefore require more infusions than is common in some physicians' clinical practices.

The study lasts for a total of 23 weeks. The ganciclovir and all clinic visits and lab work required by the study will be provided free of charge. If the drug still appears to be safe at the end of the study, all participants will be eligible for oral ganciclovir through another Syntex protocol, as long as they are willing to be followed on the protocol.

At press time the study drugs have been shipped to the seven sites listed below. We have confirmed that the study is open in Boston, Miami, and San Francisco/Davies. The Washington, D. C., site will not be enrolling patients until early May for the retinitis study, but is currently accepting participants for the food absorption study described below. We were not able to contact the San Francisco (Children's Hospital) or Galveston sites before going to press, but have been told by the clinical research associate at Syntex that they are all ready to enroll patients.

Chicago: Rush-Presbyterian-St. Luke's Medical Center. Contact person: Pam Urvanski, 312/942-5865.

Boston: Beth Israel Hospital. Contact person: Jocelyn Loftus or Mary Ann Lee, 617/735-4103.

Miami: Miami Veteran's Administration Medical Center. Contact person: Tommy Stapleton, 305/324-3267, or Debra Fertel, M. D., 305/324-4455. Please note that because this is a Veteran's Administration hospital, all veterans are eligible for the study, and individual non-veterans will be considered.

San Francisco: Davies Medical Center. Contact person: Ed Freeman, 415/565-6617.

San Francisco: Children's Hospital. Contact person: Jaime Geaga or Toby Dyner, M. D., 415/750-6529, or David Busch, M. D., 415/923-3883.

Galveston: University of Texas Medical Branch. Contact person: Karen Waterman, 409/761-4979.

Washington, D. C.: Georgetown University Hospital. Contact person: Cari O'Leary, 202/687-6845, or Anne Byrne, 202/687- 8087, or James P. Lavelle, Jr., M. D., 202/687-8826.

Additional sites in San Francisco, New York , Detroit, and San Diego are expected to receive the study drug and start enrolling patients within the next few weeks. For more information on the current status of the trial in these areas, call 800-TRIALS-A. Syntex will be updating information available through that number on at least a monthly basis.

Study of the Effect of Food on Absorption

This study is open to people who have been infected with CMV at some time in the past but do not have any signs of CMV disease. Participants must have a T-helper count above 200. The study lasts only eight days. It requires multiple blood samples on two days, single blood samples on several other days, regular telephone contact, and strict timing of medication and meals. Participants must be willing to stop taking most drugs, including all antiretrovirals, for 12 days. Because this study is not expected to provide any benefit to the participants, and does entail a significant amount of travel and inconvenience, participants will be paid $300 at the completion of the trial.

This is also an important study; it is crucial to learn how to maximize the absorption of oral ganciclovir, while minimizing its side effects. The trial is being conducted at the San Francisco (Davies Medical Center only) and Washington, D. C., sites listed above, both of which are currently enrolling participants.