US-based TransTech Pharma has entered into an agreement with the US Food and Drug Administration Division of Neurology Products, under the special protocol assessment (SPA) process, for design of a single Phase III trial of TTP488 to treat patients with mild Alzheimer's disease (AD).
SPA from the FDA is a binding agreement that the Phase III trial design, planned execution and statistical analyses are acceptable to support regulatory approval.
The randomised, double-blind, placebo-controlled, multi-centre Phase III trial will compare TTP488 5mg daily with placebo over the course of 18 months of treatment.
Around 800 patients with mild Alzheimer's disease receiving standard of care (i.e. acetylcholinesterase inhibitors) will be enrolled in the trial.
The trial's primary efficacy analysis will be based on the changes in ADAS-cog ('Alzheimer's Disease Assessment Scale - cognitive subscale') and CDR-sb ('Clinical Dementia Rating - sum of boxes').
Patient enrolment in the Phase III trial of TTP488 is expected to begin before the end of this year.
TransTech Pharma president and CFO Steve Holcombe said: "We are extremely pleased to receive agreement on the SPA and to have a clear path forward for the submission and regulatory approval of TTP488 for the treatment of patients with mild Alzheimer's disease."
TTP488 is a new small-molecule, orally active antagonist of the Receptor for Advanced Glycation Endproducts (RAGE).
According to the company, substantial data suggest that RAGE is involved in the pathogenesis of AD, and that sustained Ab interaction with RAGE at the blood-brain barrier (BBB), or in neuronal or microglial cells, is an important element of amyloid plaque formation and chronic neural dysfunction.
The company said that in a double-blind clinical trial where data was collected over 18 months, TTP488 slowed cognitive decline in patients with mild to moderate AD.