Two identical pivotal trials evaluating the safety and efficacy of autologous fibroblast therapy (Isolagen Technologies) compared with placebo are almost finished. Special attention was paid in protocol design so there would be consistency across the studies in cell harvesting and injection technique, as well as in outcomes assessments. The treatment protocol, which varies from previous studies, aims to optimize the treatment effect.
National report - Pivotal trials evaluating the efficacy and safety of autologous fibroblast therapy (AT) (Isolagen Technologies) for correcting moderate-to-severe nasolabial fold (NLF) wrinkles are now in the stage of final data collection, and outcomes analyses should be completed later this year, says Stacy R. Smith, M.D., president, Therapeutics Clinical Research, San Diego.
The two identically designed, double-blind trials were launched in October and November of 2006. They randomized a total of 421 patients to bilateral treatment with three intradermal injections of AT or placebo.
The primary efficacy assessment is being performed at six months after the third treatment, and is based on a blinded evaluator's live assessment of the NLF wrinkles and the subject's global assessment of the lower face and treatment area.
"Previous experience in small studies demonstrates it provides very good results when used to correct facial contour defects.
"These two phase 3 studies represent the two largest trials conducted to evaluate its efficacy and safety in any indication," Dr. Smith says.
AT is being evaluated under the Food and Drug Administration's Special Protocol Assessment regulations, where it will be submitted for approval as a biological product.
Carefully conceived design
The pivotal trials for treatment of NLF wrinkles were carefully designed to assure standardization of technique and outcomes assessment across all study centers, as well as to optimize the potential benefits of the AT.
The study used the six-point Lemperle Wrinkle Severity Scale (LWSS) to determine patient eligibility and for judging treatment responses. To be enrolled, patients needed to have a score of three or greater.
"The baseline requirement was set so that a two-point improvement could be obtained, since the primary efficacy assessment will compare proportions of patients in each group achieving that level of change," Dr. Smith tells Dermatology Times.
The technique for cell harvesting is intended to assure an adequate pool of viable fibroblasts.
"The protocol provides for liberal dosing of the cells to assure adequate treatment, and in contrast to some other studies evaluating traditional dermal filler materials, used a parallel group rather than a split-face design, since the mechanism for the benefit of AT involves an active host response rather than pure volume augmentation," Dr. Smith says.
"The dosing interval for this study was selected to give ample time for the new cells to be incorporated into the tissues. Viability of the transplanted cells is, of course, crucial to the success of this therapy," he says.
Disclosure: Dr. Smith is an investigator and consultant for Isolagen. He has no stock or other equity holdings in the company.