RNActive®-Derived Therapeutic Vaccine
This is a Phase I/IIa open, uncontrolled, prospective study, to be conducted in an out-patient setting. The present study is one of two clinical trials of the RNActive®-derived vaccine CV9103 being conducted concurrently in the US and Europe, which represent the first clinical trials conducted for this novel vaccine.
The Phase I part of the study consists of a staggered inclusion of subjects in two cohorts of 3, to confirm the safety of the intended dose (320 µg RNA per antigen), with a lower dose to be considered in case of dose-limiting toxicity (DLT) being reported in greater than or equal to 2 out of 3-6 subjects; in this way, the recommended dose (RD) for the Phase IIa part of the study will be established. In the Phase IIa part of the study, additional subjects will be included at the RD, to confirm the safety and explore the activity of that dose.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/IIa Study of RNActive®-Derived Therapeutic Vaccine in Advanced or Metastatic Hormone Refractory Prostate Cancer|
- Phase I: Assessment of Safety and Tolerability of the Trial Regimen [ Time Frame: At Nine Weeks with Follow Up at One Year ] [ Designated as safety issue: Yes ]
Dose Limiting Toxicity (DLT) is defined as the following treatment-related adverse events or laboratory abnormalities, graded according to NCI-CTCAE version 3.0:
- All Categories equal or greater than grade 3
- Allergy/autoimmunity equal or greater than grade 2
- Dosing delay greater than 48 hours due to toxicity All adverse events will be graded and documented according to Common Terminology Criteria for Adverse Events version 3.0.
|Study Start Date:||May 2009|
|Study Completion Date:||December 2010|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
CV9103 will be applied intradermally on three (3) or five (5) time points. Treatment with CV9103 is administered over a period of either seven (7) or twenty-three (23) weeks.
CV9103 encodes for 4 prostate specific antigens.
At present, no curative therapy is available for subjects with advanced or metastatic prostate cancer. Approximately 1 of every 3 men present with advanced or metastatic disease; therefore, current standard therapies are ineffective and new therapeutic approaches are warranted. There is ample evidence that active immunotherapy against cancer is safe and capable of stimulating potentially therapeutic immune responses in the cancer patient. Moreover, several Phase II immunotherapy trials have suggested clinical benefit by reducing the tumor mass or prolonging time to progression in subjects with advanced prostate cancer.
CV9103 is an mRNA-based vaccine for the treatment of human prostate cancer that is based on CureVac's RNActive® technology. CV9103 encodes for 4 prostate specific antigens. Because these antigens are present in prostate cancer cells, they are appropriate targets for intervention. These antigens have been shown to correlate frequently with the progression of prostate cancer, and are known to be immunogenic in humans, where they induce antigen specific T-cell or B cell expansion.
As an RNA-based vaccine, CV9103 features several advantages over other approaches: it is highly specific, there is no restriction to the patient's MHC genotype, and it does not need to cross the nuclear membrane to be active. Finally, in the absence of reverse transcriptase, RNA can not be integrated into the genome.
CV9103 will be administered in 5 doses.
|United States, Florida|
|University of Florida, College of Medicine|
|Gainesville, Florida, United States, 32610|
|Principal Investigator:||Johannes Vieweg, MD FACS||Univeristy of Florida, College of Medicine|