A Multicenter, Randomized, Double-blind Study Comparing Different FK778 Doses (Manitimus) with Tacrolimus and Steroids vs. MMF with Tacrolimus and Steroids in Renal Transplantation.
Wlodarczyk Z, Vanrenterghem Y, et al.BMC Nephrology, 13(1): 68, 2012.
Aims
To compare the efficacy and safety of three concentration-controlled dosing of FK778 with mycophenolate mofetil (MMF) in combination with tacrolimus and steroids in renal transplant recipients.
Interventions
FK778 loading dose of 600mg given four times on day 1 to 4 followed by 120 mg/day (high-level FK778 group) versus FK778 loading dose of 600mg given three times on day 1 to 3 followed by 110 mg/day (mid-level FK778 group) versus FK778 loading dose of 600mg given two times on day 1 to 2 followed by 100 mg/day (low-level FK778 group) versus MMF 1 g/day (control group). After week 6, FK778 doses were adjusted to trough ranges of 75–125 μg/mL (high-level FK778 group), 50–100 μg/mL (mid-level FK778 group) and 25–75 μg/mL (low-level FK778 group). All patients received tacrolimus and steroids
Participants
364 kidney transplant recipients.
Outcomes
The primary endpoint was the incidence of biopsy-proven acute rejection at week 24. Secondary efficacy and safety endpoints included incidence of acute rejection, time to first episode and severity of acute rejection, incidence and time to first episode of corticosteroid-resistant acute rejection, frequency of treatment failure, patient and graft survival, renal function, incidence of adverse events and cytomegalovirus and BK polyomavirus load.
Follow-up
12 months
CET Conclusions
In this well conducted trial, 3 doses of FK778 (manitimus) a malononitrilamide were assessed in association with tacrolimus and MMF and steroids but there was no proven advantage of any of the doses over conventional immunosuppression and the higher doses were associated with more adverse events. Thus this phase II clinical trial was not able to demonstrate any clear benefit of FK778 over current immunosuppression treatments and because of the requirement for intensive therapeutic drug monitoring of the FK778 a decision was made to discontinue its further clinical development.
Data analysis
Available case analysis
Trial registration
Not reported