GRWD0715-AS-01: A Multi-part, Phase I/II Study to Evaluate the Safety and Tolerability of GRWD0715 in Healthy Human Volunteers and Participants with Axial Spondyloarthritis (EAST-1)

The Purpose of the Study

Axial Spondyloarthritis (AxSpA) is a long-term condition caused by inflammation that predominantly affects the sacroiliac joints and the spine. This study evaluates an investigational oral drug called GRWD0715 to see if it is safe, well-tolerated, and effective at reducing disease activity by targeting a specific enzyme involved in the immune response.

What is GRWD0715?

GRWD0715 is a selective inhibitor of the Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) enzyme. ERAP1 is involved in trimming antigens from foreign bodies so they can be presented on the surface of a cell to trigger an immune response. In AxSpA, it is hypothesized that the immune system is mistakenly stimulated by the presentation of a specific self-peptide, which causes inflammatory symptoms. By inhibiting ERAP1, GRWD0715 aims to prevent the generation of this self-peptide and remove the stimulus driving the inflammation. Unlike many current biological therapies, this investigational drug is administered orally.

Who Can Participate?

You may be eligible to participate if you:

  • Are male or female, between 18 and 65 years of age.
  • Have a diagnosed case of Axial Spondyloarthritis with a symptom duration of at least 3 months and disease onset before age 40.
  • Test positive for HLA-B27 and have objective evidence of inflammation, such as active sacroiliac joint inflammation on an MRI or elevated C-reactive protein (CRP) levels.
  • Have an active disease score of ≥ 2.1 on the Ankylosing Spondylitis Disease Activity Score (ASDAS) while on your current treatment.
  • Have had an inadequate clinical response or intolerance to at least one Non-Steroidal Anti-Inflammatory Drug (NSAID).
  • Note: Participants may have received 1 (or 2 in Australia) prior biologic or targeted synthetic DMARDs, provided they were discontinued due to intolerance or inadequate efficacy and a required washout period is completed.

What to Expect During the Trial

  • Study Design: This is a multi-part Phase I/II study known as EAST-1. Depending on the cohort, participants with AxSpA will join either a multiple ascending dose group, a safety expansion cohort, or a randomized, placebo-controlled expansion cohort.
  • Dosing: The study drug is taken orally.
  • Monitoring: Safety is the primary goal. Participants will be closely monitored for safety and tolerability, as well as for efficacy measures such as improvements in ASAS clinical scores and MRI activity of the spine and sacroiliac joints.

Why Participate?

By participating in the EAST-1 trial, you will be contributing to the development of a completely new, targeted treatment pathway for AxSpA. While there is no guarantee of direct health benefits, the data collected will help researchers determine if inhibiting the ERAP1 enzyme is a safe and effective way to halt the immune system’s attack on the body’s joints and improve the quality of life for those living with the condition.

https://clinicaltrials.gov/study/NCT07047703