The open-label study (NCT03831438), which is currently recruiting participants, was designed to assess the safety and tolerability of AVID200, as well as to identify the optimal dose to be used in further studies.
The trial is being conducted at the Hospital of Special Surgery in New York City and at the University of Pittsburgh Medical Center, and is expected to enroll approximately 24 adult patients with diffuse cutaneous SSc.
TGF-beta is among the pro-fibrotic molecules that are known to be involved in skin fibrosis, being a powerful stimulus for collagen synthesis and cell proliferation — hallmark features of SSc. In particular, TGF-beta 1 and 3 correlate positively with SSc severity.
AVID200 was engineered to specifically block the activity of TGF-beta 1 and 3, while sparing other isoforms of this signaling molecule that do not contribute to the fibrotic process, and are required for normal cardiac function and immune system regulation.
“For decades, safe and potent neutralization of TGF-beta has been the holy grail for the treatment of fibrotic diseases,” Ilia Tikhomirov, president and CEO of Forbius, said in a press release. “AVID200 has the potential to transform the treatment of many diseases and is the first of several new generation TGF-beta inhibitors being developed by Forbius.”
Given its targeted selectivity, AVID200 can overcome the major limitation of prior non-selective TGF-beta inhibitors, which were associated with significant unwanted side effects. Therefore, AVID200 holds the potential to represent an effective and well-tolerated therapeutic strategy in a variety of clinical settings.
In the trial, participants will be injected intravenously with AVID200 once every two weeks. Upon completion of the first treatment cycle, if the clinical data does not reveal signs of toxicity or safety issues, the patients will receive two additional treatment cycles with AVID200, until they reach an overall treatment period of six weeks.
Besides assessing AVID200’s safety, the researchers will also explore the stability, metabolism, and excretion of the agent, as well as early evidence of its anti-fibrotic activity.
“The basic defect in SSc and most other fibrotic diseases is increased TGF-beta signaling. Selective TGF-beta inhibition by AVID200 could rapidly reverse fibrosis, and I am keen to investigate the potential of AVID200 to transform the treatment of SSc,” said Robert Lafyatis, MD, Medsger professor and director of the Scleroderma Center at the University of Pittsburgh Medical Center, and coordinating principal investigator of the study.
For more information about the trial and how to participate, visit its webpage here.