Date: 2014-02-18
Type of information: Results
phase: 3
Announcement: results
Company: Bayer (Germany)
Product: BAY94-9027 [recombinant human factor VIII (rFVIII) - damoctogog alfa pegol]
Action
mechanism: BAY94-9027 is engineered to extend the circulating half-life while preserving full biologic activity through site-specific pegylation. This site-specific pegylation is achieved by inserting a single cysteine (amino acid) on the factor VIII surface, which serves as an attachment site for a polyethylene glycol (PEG) polymer.
Disease: hemophilia A
Therapeutic area: Hematologic diseases - Genetic diseases
Country: international study
Trial
details: PROTECT VIII (PROphylaxis in hemophilia A patienTs via directly pEgylated long-aCTing rFVIII) is a multicenter, multinational, partially randomized, open-label trial with four treatment arms evaluating the safety and efficacy of the site-specific PEGylated factor VIII in previously treated adults and adolescents with severe hemophilia A. 134 subjects were treated in the study. Subjects selected either on-demand or prophylactic treatment upon enrollment. All subjects in the three prophylaxis arms began treatment with the site-specific PEGylated recombinant human factor VIII twice per week. After a ten-week period subjects experiencing more than one bleed during this assessment period stayed on two infusions per week at a higher dose and all other subjects were randomized to either every five- or seven-day treatment for six months. After randomization, subjects who assessed their bleeding control as not adequate could leave the assigned treatment regimen and increase their infusion frequency.
PROTECT VIII Kids is a multicenter, multinational, partially randomized, open-label trial evaluating the safety and efficacy of BAY 94-9027, at different dosing frequencies, in both prophylactic and on-demand treatment of bleeding in male children with severe hemophilia A. The study will enroll 50 previously treated patients (PTP) worldwide. Subjects will be children up to 12 years of age, who have severe hemophilia A (<1% FVIIIc) and a documented history of at least 50 exposure days (ED) with any FVIII product. Subjects who are currently treated with primary or secondary prophylaxis or are not receiving a regularly prescribed infusion regimen (on-demand or intermittent prophylaxis) may be enrolled. The total duration of the individual treatment is 50 exposure days.
Subjects will also be offered participation in an optional extension study, during which observations will be collected for at least 50 additional exposure days.
Latest
news:
* On February 18, 2014, Bayer HealthCare has announced positive results from the PROTECT VIII trial evaluating the company’s investigational site-specific PEGylated recombinant human factor VIIIcompound BAY94-9027. The study met its primary objective of protection from bleeds with fewer infusions. In the study, the site-specific PEGylated factor VIII provided protection from bleeds when used prophylactically every seven days, every five days, and twice per week. The compound was also effective for treatment of acute and breakthrough bleeds with 91 percent of events resolved with one or two infusions. 88 percent of subjects met the pre-defined criterion of bleeding control in the ten-week initial assessment period and qualified for randomization. All subjects receiving infusion every five days (n=43) remained in this treatment arm. 44 percent of subjects in the every-five-day treatment arm experienced no bleeds. A median annualized bleeding rate (ABR) of 1.9 was observed in this treatment arm. 74 percent of the subjects receiving infusion every seven days (n=43) remained in their treatment arm. 37 percent experienced no bleeds. A median ABR of 3.9 (including non-completers) was observed in this treatment arm. The 13 subjects who remained in the two times per week treatment arm, because of their high bleeding rate during the assessment period, reduced their median ABR from 17.4 to 4.1 following dose increase. By comparison, subjects who were treated on-demand (n=20) had a median ABR of 23. The safety objectives were also met. The site-specific PEGylated factor VIII was well tolerated. Subjects were treated for up to 36 weeks; no inhibitors to factor VIII were confirmed. Two drug-related cases of hypersensitivity reactions were reported. One was assessed as serious, but resolved without medical intervention. No other serious drug-related adverse events were reported. Detailed data are scheduled for presentation at the World Federation of Hemophilia Meeting in May 2014 in Melbourne, Australia. Bayer plans to submit marketing authorization applications to regulatory authorities in the U.S., Europe and other countries in the second half of 2015. Evaluation of safety and efficacy during major surgery and PROTECT Kids in pediatric patients are ongoing, and a study in previously untreated patients is planned. * On July 8, 2013, following the completion of enrollment of adult patients with hemophilia A into the PROTECT VIII trial (PROphylaxis in hemophilia A patienTs via directly pEgylated long-aCTing rFVIII), Bayer HealthCare has announced that the company has started to enroll children in an international Phase III trial to evaluate its investigational compound BAY 94-9027 for the treatment of hemophilia A. The PROTECT VIII Kids trial is designed to investigate whether BAY 94-9027 can be used prophylactically to prolong duration of protection from bleeding events for up to one week, while also being used to treat acute bleeds. * On July 8, 2012, Bayer has started to enroll patients in an international Phase III trial to evaluate BAY94-9027 for the treatment of hemophilia A. The PROTECT VIII (PROphylaxis in hemophilia A patienTs via directly pEgylated long-aCTing rFVIII) trial is designed to investigate whether BAY94-9027, a recombinant human factor VIII (rFVIII), can prolong the duration of protection from bleeds and with less frequent Infusions when used prophylactically, while also having the ability to treat acute bleeding events.
