LEXINGTON, Mass.—Concert Pharmaceuticals, Inc. reports today that it has completed patient enrollment of its Phase 2 clinical trial to evaluate CTP-692 as an adjunctive treatment in patients with schizophrenia. Topline data from the trial are expected in the first quarter of 2021.
“CTP-692 offers a potential new mechanism to treat schizophrenia that, when combined with existing antipsychotic medications, may more broadly address disease symptoms than is currently possible,” said James V. Cassella, Ph.D., chief development officer of Concert Pharmaceuticals.
The underlying rationale of current antipsychotic therapies for schizophrenia is that excessive dopaminergic neurotransmission and dysfunctional D2 receptor signaling are believed to play key pathophysiological roles in the disease. Consequently, all approved typical and atypical antipsychotics possess some level of D2 antagonist activity.
Deficient glutamatergic neurotransmission mediated by the NMDA receptor is believed to be another underlying cause of schizophrenia. Individuals with schizophrenia have low plasma and cerebrospinal fluid levels of D-serine, a key molecule which activates NMDA receptors in areas of the brain that are widely believed to play key roles in schizophrenia.
CTP-692 is an investigational deuterium-modified form of D‑serine that offers an entirely new mechanism of action to potentially treat schizophrenia. Administration could help enhance NMDA neurotransmission, potentially more safely than using unmodified D-serine. CTP-692 is initially being developed as an adjunctive therapy with the potential to improve positive and negative symptoms, as well as cognitive function in patients with schizophrenia.
The double-blind, randomized, placebo-controlled Phase 2 trial is designed to evaluate the safety and efficacy of CTP-692 as an adjunctive treatment in adult patients with schizophrenia. A total of 325 patients on a stable course of an antipsychotic medication were randomized to receive 1, 2, or 4-gram doses of CTP-692 or placebo once-daily. The primary outcome measure is the change in the Positive and Negative Syndrome Scale total score at 12 weeks, compared to baseline.
“We designed the Phase 2 study to assess CTP-692’s potential to improve on the primary symptom domains in schizophrenia, including positive and negative symptoms and cognitive function, when added to existing antipsychotic treatments,” Cassella pointed out. “Maintaining the integrity of our trial has been a top priority, and we’re grateful to the study sites and patients for enabling us to complete enrollment and keep the study progressing forward despite the impact of COVID‑19.”