Date: 2011-01-17
Type of information:
phase: 2
Announcement: results
Company: Agennix (Germany)
Product: talactoferrin
Action
mechanism: Talactoferrin is an oral biologic therapy with immunomodulatory and antibacterial properties, which is being studied for the treatment of cancer and severe sepsis.
Disease: severe sepsis
Therapeutic area: Infectious diseases
Country: USA
Trial details: The double-blind, placebo-controlled trial evaluated talactoferrin versus placebo in 190 adult patients with severe sepsis enrolled at 25 leading centers across the U.S.
Latest
news: Agennix has announced that new and more detailed data from a Phase II trial in severe sepsis with talactoferrin, an oral biologic therapy with immunomodulatory and antibacterial properties, were presented at the 40th Critical Care Congress of the Society of Critical Care Medicine in San Diego, California.
As previously reported, the Phase II trial achieved its primary endpoint of a reduction in 28-day all-cause mortality (13% absolute reduction). The presentation reported that the effect of talactoferrin on reduction in all-cause mortality was sustained at three and six months. The reduction in mortality was seen in patients with and without cardiovascular dysfunction. However, there appeared to be a greater, significant effect in patients without cardiovascular dysfunction, which is consistent with the effect seen on 28-day mortality.
The following results were reported: Three-month all-cause mortality was 29.7% in the placebo arm compared to 17.9% in the talactoferrin arm, an absolute reduction of 12% (two-tailed p-value adjusted for cardiovascular dysfunction = 0.09).
For patients with cardiovascular dysfunction, there was an absolute reduction of 7% in three-month all-cause mortality with 32.8% in the placebo arm compared to 26.3% in the talactoferrin arm.
For patients without cardiovascular dysfunction, there was an absolute reduction of 18% with 23.3% in the placebo group and 5.3% in the talactoferrin group.
At six months, there was a statistically significant reduction in all-cause mortality from 35.6% in the placebo arm to 21.1% in the talactoferrin arm, an absolute reduction of 15% (p-value = 0.04). For patients with cardiovascular dysfunction, there was an absolute reduction of 10% in six-month all cause mortality with 38.3% in the placebo arm compared to 28.1% in the talactoferrin arm. For patients without cardiovascular dysfunction, there was an absolute reduction in six-month all cause mortality of 20% with 30.0% in the placebo group and 10.5% in the talactoferrin group.
The above analyses were all conducted on a modified intent-to-treat (ITT) as treated basis, meaning that patients were evaluated based on the treatment they actually received (talactoferrin or placebo) during the first week on study. Three-month and six-month all-cause mortality were secondary endpoints in the trial.
Talactoferrin was very well tolerated in the study with no significant differences in adverse events between the two treatment arms. Of those adverse events considered to be possibly related to treatment, the most frequently reported category in both treatment groups was gastrointestinal disorders (5.5% of patients in the talactoferrin arm and 5.4% in the placebo arm). There were no serious adverse events considered to be related to treatment with talactoferrin.
The Phase II trial was primarily funded by a grant from the U.S. National Institutes of Health.
Agennix plans to initiate the Phase II portion of a Phase II/III trial with talactoferrin in severe sepsis in March or April 2011.
