Biotherapeutic Shows Efficacy in TX of Bacterial Vaginosis

A live biotherapeutic product containing Lactobacillus crispatus CTV-05, when combined with metronidazole gel, resulted in a lower recurrence of bacterial vaginosis at 12 weeks over placebo, according to results of a phase IIb trial. Moreover, the product, called Lactin-V, appeared to be effective through week 24.

In the randomized, double-blind, placebo-controlled trial, women 18-45 years old with a diagnosis of bacterial vaginosis were assigned to receive either the study drug, Lactin-V, or placebo for 11 weeks following treatment with vaginal metronidazole gel.

“Overall, adherence to the assigned treatment was high,” Craig R. Cohen, MD, from the Departments of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco, and colleagues wrote in The New England Journal of Medicine. “In the Lactin-V group, L. crispatus CTV-05 was detected in almost 80% of the participants at the week 12 visit and in almost 50% of the participants at the week 24 visit after completion of the 12-week post-treatment phase of the trial.”

Lactin-V “is composed of a powder containing 2×10⁹ colony-forming units (CFU) of L. crispatus CTV005 preserved with inactive ingredients and is administered with the use of a prefilled vaginal applicator,” the study authors explained. The biotherapeutic is intended to “promote a community state type (i.e., microbial composition) with a predominance of L. crispatus after treatment with vaginal 0.75% metronidazole gel.”

Previous trials of the therapeutic showed no serious or grade 3 adverse events and the current trial builds upon findings from the previous phase IIa trial to determine how Lactin-V would fare in reducing the incidence of recurrent vaginosis.

Vaginosis is a very common condition globally, affecting some 15%-50% of women of reproductive age. And, even though antibiotics show efficacy, the condition often recurs in 20%-75% of women within three months of treatment. The study authors pointed out that bacterial vaginosis is associated with an increased risk of sexually transmitted infections (STI), such as HIV, “as well as premature birth and other reproductive health sequelae.” Moreover, it can affect a woman’s emotional, sexual, and social well-being, as well as pose an economic burden on the healthcare system, Cohen and colleagues noted.

The 228 women who were randomized 2:1 (152 in the Lactin-V group:76 in the placebo group) to either the study drug or placebo had to meet at least three of four Amsel criteria and have a Nugent score of 4-10 at screening. They also had to test negative for STIs. Within 30 days prior to their screening visit, the women completed a standard five-day course of vaginal 0.75% metronidazole.

The primary efficacy outcome of the study was the percentage of participants with a recurrence of bacterial vaginosis at any follow-up as well as at the 12-week visit and the secondary outcomes were the percentage with recurrence of the condition at the 24-week follow-up after the 12-week post treatment phase of the trial. Other secondary outcomes included the percentage of participants with detectable L. crispatus CTV-05 at 12 weeks and 24 weeks.

Eighty-eight percent of the women in the Lactin-V group and 84% of those in the placebo group were evaluated for the primary outcome.

Among the trial’s findings:

• At week 12 there was a recurrence of bacterial vaginosis in 46 (30%) of those in the Lactin-V group and in 34 (45%) of the placebo group (risk ratio, 0.66; 95% confidence interval [CI], 0.44 to 0.87; P = 0.01).
• At week 24, those who did not have a recurrence at week 12 — 13 (12%) of 106 women in the Lactin-V group and 7 (17%) of 42 women in the placebo group had a recurrence, with a risk ratio of 0.73 (95%CI, 0.54-0.92).
• L. crispatus CTV-05 was detected in 79% (at week 12) to 84% of participants in the Lactin-V group at weeks 4, 8, and 12, with 48% in the study drug group having L. crispatus CTV-05 detected at week 24.

• The placebo group had a much lower detection of L. crispatus CTV-05 — 2%-6% of participants at weeks 4, 8, and 12 and 2% at week 24.

“There were no apparent associations between the detection of L. crispatus CTV-05 at week 12 or week 24 and adherence to the assigned treatment occurrence of menses since the last visit, or occurrence of sex without the use of a condom,” Cohen and colleagues wrote.

The study authors noted that the incidence of treatment-related adverse events was similar between the two study arms by week 24 — 132 participants (87%) in the Lactin-V group and 60 participants (79%) in the placebo group (risk ratio, 1.11; 95% CI, 0.98-1.33; P = 0.12).

Abnormal vaginal discharges, abnormal vaginal odor, external genital irritation, and genital itching were the most common adverse events, and of systemic AE’s abdominal pain or cramps, headache, and frequent urination were most common.

“In the current trial, the initial dose of Lactin-V or placebo was administered within 48 hours after the last dose of vaginal metronidazole gel, and the frequency of dosing after the first week was increased from once weekly to twice weekly through week 11,” the study authors wrote. “We did not find that the occurrence of menses since the last visit or the occurrence of sex without the use of a condom affected the detection of L. crispatus CTV-05.”

They noted that the treatment was evaluated at 11 weeks and 24 weeks of follow-up and that “further study should be considered to assess longer-term sustainability of colonization and prevention of bacterial vaginosis.”

Lactin-V is not yet approved by the FDA and the study authors noted in a press statement that the agency will likely require a successful phase III trial prior to approval.

“This is an entirely new approach that strengthens the vaginal microbiome against infections,” said Anke Hemmerling, MD, one of the study authors. “This could be a breakthrough for the long-term prevention of [bacterial vaginosis].”

1. A live biotherapeutic product containing Lactobacillus crispatus CTV-05, when combined with metronidazole gel, resulted in a lower recurrence of bacterial vaginosis at 12 weeks over placebo, and it appeared to be effective through week 24.

2. Be aware that Lactin-V is not yet FDA approved and will likely still need to show efficacy in a phase III trial.

Candace Hoffmann, Managing Editor, BreakingMED™

Cat ID: 191

Topic ID: 83,191,190,191,192,925