Phase III registration trial
ENGLISH DEUTSCH
WILEX conducted a Phase III registration trial with REDECTANE®. In total 226 patients suspected of having kidney cancer were enrolled in more than 14 centres in the USA. Patients included were scheduled for complete or partial surgical removal of the affected kidney. They were imaged with computer tomography (CT) and REDECTANE® (PET/CT) prior to surgery to examine whether they have clear cell renal cell carcinoma. The trial will evaluate whether imaging with REDECTANE® can improve the diagnosis in comparison to the current standard (CT alone).
FIG 1: Contrast CT in a patient with a renal mass in the right kidney. FIG 2: REDECTANE® PET/CT clearly identifies ccRCC in the right kidney. Image courtesy of Memorial Sloane-Kettering Cancer Center, New York, NY
Status
In May 2010 WILEX published final data of the Phase III trial with REDECTANE®. REDECTANE® fulfilled expectations in distinguishing clear cell from non-clear cell renal cell carcinoma. The results of the study demonstrate that PET/CT with REDECTANE® lead to a significantly improved diagnosis in comparison to CT alone.
In contrast to the preliminary data published in November 2009, the endpoint sensitivity, the correct diagnosis that clear cell renal cell cancer is present, was reached with statistical significance (p value, p) (p=0.016) compared to CT. The study endpoint specificity, the correct diagnosis that clear cell renal cell cancer is not present, was confirmed with a highly statistical significance (p<0.001). To rule out that the superiority of REDECTANE® resulted from the poor performance of CT, the endpoints of REDECTANE® were also compared to an arbitrary value of 75% for specificity and sensitivity as defined in the study protocol. REDECTANE® achieved sensitivity of 86% (p=0.002) and specificity of 87% (p=0.057).
On 17 June 2011, WILEX and its partner IBA released information on the pre-BLA meeting with the FDA and the next steps in the approval process for REDECTANE®. Pre-BLA meetings serve to discuss the application for approval of a product and the approval process in advance of filing. The FDA confirmed during the discussions at this meeting that the Phase III REDECT trial delivers reasonable evidence of the diagnostic efficacy and safety of REDECTANE®. Two issues remain to be resolved by WILEX and its partner IBA. The FDA suggested that WILEX and IBA might consider an outcomes based study to provide additional evidence of clinical benefit before BLA filing. WILEX and IBA agree with the FDA that a trial with a clinical benefit outcome could represent the next logical step in REDECTANE’s development. WILEX, IBA and external medical advisors however are of the opinion that such a trial should be conducted as a Phase IV trial after market approval. WILEX and IBA will first discuss the trial design and strategy with the Medical Advisory Board and subsequently with the FDA. The second set of issues discussed with the FDA concerns matters related to the manufacturing of REDECTANE®. WILEX and IBA will make the required data available to the FDA in the next months.
Specific protocol assessment
WILEX has received a special protocol assessment (SPA) from the US Food and Drug Administration (FDA) for this Phase III registration trial. With this SPA the FDA confirms that the design and planned analysis of the clinical trial adequately address the requirements for a regulatory submission for REDECTANE®. The FDA is considered to be bound by this protocol assessment as part of the approval process.
