L-697,661 Phase II Trials at NIH, and in Birmingham

A phase II trial of L-697,661 (also called L-661), an important new antiviral developed by Merck & Co., will begin soon at the U. S. National Institute of Allergy and Infectious Diseases (NIAID) near Washington, D. C. ; about 75 volunteers will be enrolled. A similar but not identical trial will be conducted at the University of Alabama in Birmingham.

NIAID Trial (Near Washington, DC)

To be eligible for the NIAID trial, volunteers must be HIV- positive, have a T-helper count of over 200, and have a positive titer for plasma viremia. (The Birmingham trial may later accept persons with lower T- helper counts.) Volunteers must be between 18 and 60 years old, and either never have taken AZT or have taken it for no more than a total of six months; they must not have a history of serious intolerance to AZT. They cannot take any investigational drug, AZT, or other HIV treatment within four weeks of beginning the study. They cannot currently have any OI, dementia, wasting syndrome, or malignancy (other than muco- cutaneous KS). They cannot have significant kidney or liver disease.

The reason this particular trial excludes persons who have taken AZT for more than six months is that viral resistance to AZT may have developed after long-term use. Because anyone entering this trial might be assigned to the AZT arm, such resistance could falsely bias the results against AZT.

Once in the study, volunteers will be randomized to five groups: 25 mg of L-661 twice a day, 100 mg three times a day, 500 mg twice a day, AZT 100 mg five times a day, or placebo. After 12 weeks, those receiving either the placebo or AZT will be re-randomized to one of the three L-661 groups. The study will be evaluated every six weeks, and continued for another six-week period as long as results warrant. It will look for changes in "surrogate markers" (such as T-helper count, plasma viremia, etc.) .

All drugs are taken orally. No hospitalization is required, but weekly visits are necessary during the first part of the trial. To obtain the best possible data, volunteers will keep diaries and work closely with a case manager.

L-661 has been given in single-dose or short-term studies to several dozen people so far, with no significant adverse effects.

For more information, or to volunteer for this study, call Donna O'Neill, R. N., at 800/772-5464 ext. 312 or 301/402-0980 ext. 312, or Susan Haneiwich at the same phone numbers, ext. 403.

Birmingham, Alabama Trial

The trial at the University of Alabama is similar; however, there will be no placebo. Three doses of L-661 will be compared against the usual dose of AZT. This trial has just begun; it is seeking 60 volunteers with T-helper counts between 200 and 500. Later, a similar trial in Birmingham will need 60 additional volunteers with T- helper counts under 200.

The trial for persons with lower T-helper counts is planned to start in about a month. The reason for starting first with T-helper counts from 200 to 500 is to get good information quickly about any toxicity of the drug. Such side effects could be masked by AIDS symptoms in persons who are more seriously ill.

Weekly visits are required during the first six weeks of these trials. Because of the safety precautions needed during early experience with a new drug, it is strongly preferred that volunteers stay in Birmingham during the first six weeks they are on the study.

For more information, or to volunteer for the Birmingham trial, call 800/822-8816, or 205/934-9999, and ask for information about the new L-661 study.

L-Drug Support Group

An "L-drug" support group for persons in any trial of L- 661 (or of the related drug, L-697,639), or who are considering volunteering, has been organized by AIDS activist Bill Bahlman. He can be reached by mail at 496-A Hudson St., Suite J-11, New York, NY 10014.

Comment

L-661 is one of the most important AIDS treatments now being tested. The NIAID and Birmingham trials are very well designed to obtain information quickly without undue risks to participants:

* A placebo is often necessary to obtain definitive data quickly -- which is especially important with this drug. The NIAID placebo arm will last for only 12 weeks (a limited risk) and then those in that arm will be given the active drug. Since there are five arms to the study, there is only one chance in five of getting the placebo. By contrast, previous studies often asked persons with serious HIV disease to take placebos for much longer, sometimes for two years.

* These studies are designed to look for improvement in bloodwork or in clinical condition of patients, instead of looking for disease progression or death, as phase II studies have often done. With "surrogate markers" instead of death or serious disease, statistically reliable results can be obtained much faster, and with fewer volunteers (which avoids additional delays in organizing and conducting the trials).

* These study will produce drug-drug and (in the NIAID study) drug-placebo comparisons, as well as dose- response information. The doses, based on earlier laboratory, animal, and human studies, vary over a wide range, which is appropriate with this drug, since the range between effective and toxic doses may be very large. Dosage information will be obtained quickly, early in the clinical-trials process; then it will be available to guide all later trials or other uses of the drug.

* This trial will produce data continuously, because of the six-week evaluations; it will not be necessary to wait for a year, two years, or more to know whether the drug is working. And there is no arbitrary endpoint; the study will continue as long as warranted. The same trial which produces short-term results rapidly will go on to produce long-term results as well, instead of wasting this opportunity, as most studies in the past have done. This design also provides the drug to volunteers, instead of cutting them off at the "end" of the study.