Drug of dreams’ preps for first large-scale trial: Study to begin this year
Moxifloxacin to debut soon in Study 27
Moxifloxacin, the new anti-TB drug candidate that has many researchers so excited that they’re ready to uncork the champagne, should start enrolling for its first full-scale trial within the next six months, TB experts at the Center for Disease Control and Prevention (CDC) confirm. Experts hope that the drug will prove to be a terrific new sterilizing agent — at least as good as rifampin, perhaps even better. If so, that would open the way to shorter treatment, undoubtedly the Holy Grail of current TB drug research.
"When you think about all the drugs that stand a chance of paying off in the short term, this is certainly the most exciting one we have," says Rick O’Brien, chief of the research and evaluation branch of the Division of TB Elimination at the CDC in Atlanta.
At the Fourth World Congress on TB held in Washington, DC, in June, plaudits for the Bayer Pharmaceutical antibiotic flowed thick and fast. No less an eminence than Jacques Grosset, from Hôpital Pitie-Salpetriere in Paris who recently joined TB researchers at Johns Hopkins University in Baltimore, concluded his presentation on the drug by announcing, "I think this may be the drug of my dreams!"
Upping conversion rates by 15%?
Away from the hustle and bustle, details for the planned trial of moxifloxacin were perking along without a hitch. The CDC’s TB Trials Consortium (TBTC) recently finished thrashing out a protocol for Study 27, a large safety and efficacy trial expected to enroll between 500 and 600 patients, says O’Brien. That protocol is expected to win final approval by October, when the TBTC steering committee meets in Montreal.
Better yet, negotiations with Bayer, which owns and makes the drug, also have successfully wrapped up, says O’Brien. At first, the German-based pharmaceutical giant was hesitant about trying to license its drug for use in the TB field. However, post-marketing data on moxifloxacin’s safety and tolerability have been so positive that the company finally decided to plunge ahead, she says.
What researchers want to find out from Study 27 is whether by substituting moxifloxacin for ethambutol, more patients will convert their sputum-smear cultures sooner. What researchers are banking on is that two-month sputum conversion rates will rise from where they stand now — about 75% of patients — up to as high as 85% or even 90%. If that happens, it’ll be time to start thinking about the next exciting step — radically shortening the onerous four-month continuation phase of therapy.
Subbing for ethambutol
Study 27 is expected to consist of four arms, each with about 125 patients, O’Brien says:
• Two experimental arms in which patients will get moxifloxacin instead of ethambutol (along with the standard remaining three drugs, isoniazid, rifampin, and pyrazinamide);
• Two more arms in which patients get ethambutol (along with the other standard three).
One of each group will get daily therapy for two months; and one of each will get daily therapy for two weeks, with intermittent treatment (at a frequency of either twice-weekly or, more likely, thrice-weekly) for six weeks. That way, the trial will be able to sift out the impact of substituting moxifloxacin, and also look at whether daily or intermittent therapy works best, says O’Brien.
The dosage will be the standard adult dose used for other, non-TB-related indications. "Although you’re always looking for toxicity in such a trial, apparently this has an extremely good safety profile," notes O’Brien.
Still unresolved is whether the upcoming trial will enroll patients in Uganda, at the National Institutes of Health’s (NIH) site in Kampala. Arranging a large-scale TB collaboration with the NIH’s TB Research Unit has been one of the Trials Consortium’s longstanding goals, not only because it would speed enrollment, but because such a collaboration would afford a ready supply of HIV-infected patients.
In the long term, moxifloxacin will probably also be explored in TBTC trials as a companion to rifapentine, researchers say. With their long half-lives, using the two drugs almost surely will be at least one sure ticket to a less frequent dosing schedule. As if all this weren’t enough, the pair also holds out strong promise as a much-shortened treatment for latent TB infection.
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