Repligen Corporation announced the initiation of its Phase 3 clinical trial program for secretin in pediatric autism. Based on feedback from the Food and Drug Administration (FDA), the Company intends to conduct two clinical trials each of which will enroll approximately 175 children aged 2 years 8 months to 4 years 11 months 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 reciprocal social interaction as measured with the Autism Diagnostic Observation Schedule (ADOS) and the Clinical Global Impression of Change (CGI). Secondary endpoints will include improvements in language and improvements in behavior.
The trials will be carried out at 15 to 20 medical centers in the United States. The two trials are identical in design with the exception that one of the trials will enroll only children with gastrointestinal symptoms.
The Company also announced additional analysis of the data from its Phase 2 trial including an extended analysis of the effect of age on the response to secretin. The Phase 2 study evaluated three administrations of secretin or a placebo in 126 patients aged 3 years to 6 years 11 months with moderate to severe symptoms of autism and gastrointestinal disorders.
Prior analysis of the Phase 2 clinical trial data identified a subset of 64 patients who had normal levels of biological markers of colitis or pancreatic insufficiency, in which there was a statistically significant effect of secretin treatment in the ADOS social interaction scale (p=0.02). The effect on age in this subgroup was similar to that observed in all patients. The Phase 3 trial will utilize the biomarkers identified in the Phase 2 trial as inclusion criteria.
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 Aricept was approved for Alzheimer's disease based on a Clinical Global Impression and symptom improvements recorded on the cognitive scale of the Alzheimer's Disease Assessment Scale.
The Phase 3 trial will use CGI and the ADOS reciprocal social interaction scale as the 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. ADOS is a standardized clinical instrument for the diagnosis of autism based on a structured interaction between a trained psychologist and the child. The interaction consists of a series of tasks designed to assess deficits in communication and reciprocal social interaction.
ADOS is widely accepted as the "gold standard" for the assessment of autistic patients in clinical research. The ADOS reciprocal 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. Deficits in social interaction skills are a core symptom of autism.