Notice that the kids in this sample are younger and have GI problems.
Repligen Announces Phase 3 Clinical Trial Plans for Secretin in Autism
NEEDHAM, MA - November 1, 2001 - Repligen Corporation (Nasdaq: RGEN) announced today Phase 3 clinical trial plans for secretin in pediatric autism. Based on feedback from the Food and Drug Administration ("FDA"), the Company intends to conduct two clinical trials which will enroll a total of approximately 300 children aged 3 to 6 with moderate to severe symptoms of autism. Each patient will be comprehensively evaluated at baseline, receive six injections of secretin or a placebo over 18 weeks and then be reevaluated for improvements in the symptoms of autism. The primary endpoints will be improvements in the parental Clinical Global Impression of Change and improvements in social interaction as measured with the Autism Diagnostic Observation Schedule. The company intends to submit a complete clinical protocol to the FDA by the end of the year.
The Phase 3 trial design is based on results obtained in the Phase 2 trial and feedback from the FDA. The double-blind, placebo-controlled Phase 2 study evaluated three administrations of secretin or a placebo in 126 patients aged 3 to 6 with moderate to severe symptoms of autism and gastrointestinal disorders. Patients treated with secretin showed a statistically significant improvement in a parental Clinical Global Impression of Change ("CGI", p=0.02) and a trend towards improvement in the social interaction scale of the Autism Diagnostic Observation Schedule ("ADOS", p=0.11). In a subset of 64 patients who had normal levels of biological markers of colitis or pancreatic insufficiency, there was a statistically significant effect of secretin treatment in four endpoints including CGI (p=0.001) and the ADOS social interaction scale (p=0.02). The Phase 3 trial will utilize the biomarkers identified in the Phase 2 trial as inclusion criteria. The primary endpoints for the Phase 3 trial will be CGI and the ADOS social interaction scale. Improvements in receptive and expressive language will be a secondary endpoint. Pending approval of the FDA, patients will be enrolled at 15 to 20 medical centers in the United States.
"Based on discussions with the FDA, we believe that we have reached a consensus on the critical elements of a Phase 3 clinical trial program: number of patients, inclusion criteria, treatment protocol and endpoints," stated Dr. Walter C. Herlihy, President and CEO of Repligen. "We believe that if these trials are successful, they will provide the clinical data to support a New Drug Application."
The Phase 3 strategy is patterned after the design of Phase 3 trials of other currently approved drugs for diseases of behavior or cognition such as Alzheimer's disease, depression or schizophrenia. These drugs were approved by the FDA on the basis of two trials which met a dual primary endpoint consisting of a Clinical Global Impression and a second assessment with a quantitative scale of symptoms specific to a particular disease. For example, Pfizer's drug Ariceptā was approved for Alzheimer's disease based on a Clinical Global Impression and, secondly, symptom improvements recorded on the cognitive scale of the Alzheimer's Disease Assessment Scale.
The Phase 3 trial will use CGI and the ADOS social scale as primary endpoints. CGI is a standardized assessment of the global change in symptoms in which a patient is rated as "very much improved," "much improved," "minimally improved," etc. It has been used as a primary endpoint in the FDA approval process for many drugs that target behavioral or cognitive symptoms. ADOS is a standardized clinical instrument for the diagnosis of autism based on a structured interaction between a psychologist and the child. The interaction consists of a series of tasks designed to assess deficits in communication and social interaction. ADOS is widely accepted as the "gold standard" for the assessment of autistic patients in clinical research. The ADOS social interaction scale is a series of activities which enable a clinician to evaluate eye contact, facial expressions, shared enjoyment in interaction, showing of toys or objects, the initiation of joint attention, the response to joint attention and the quality of social overtures.
The Principal Investigator for the Phase 3 study will be Dr. Margaret Bauman. Dr. Bauman is a neurologist who is affiliated with Massachusetts General Hospital and Harvard Medical School and she also directs a clinic in Massachusetts which treats individuals with autism. Dr. Bauman was the first researcher to identify the parts of the brain affected in autism and the first to describe the cytopathology of autistic brains, results which form the basis of the current understanding of the neurobiology of autism. The primary psychometric consultant for the trial will be Helen Tager-Flusberg, Ph.D. who participated in the design of the Phase 2 trial. Dr. Tager-Flusberg is the Director of the Laboratory on Developmental Cognitive Neurosciences at Boston University School of Medicine and is a Principal Investigator of an NIH-funded Collaborative Program of Excellence in Autism.
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